Journal articles on the topic 'Rearrangement'
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1
Greaney, Michael F., and David M. Whalley. "Recent Advances in the Smiles Rearrangement: New Opportunities for Arylation." Synthesis 54, no. 08 (December 1, 2021): 1908–18. http://dx.doi.org/10.1055/a-1710-6289.
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AbstractThe Smiles rearrangement has undergone a renaissance in recent years providing new avenues for non-canonical arylation techniques in both the radical and polar regimes. This short review will discuss recent applications of the reaction (from 2017 to late 2021), including its relevance to areas such as heterocycle synthesis and the functionalization of alkenes and alkynes as well as glimpses at new directions for the field.1 Introduction2 Polar Smiles Rearrangements3 Radical Smiles: Alkene and Alkyne Functionalization4 Radical Smiles: Rearrangements via C–X Bond Cleavage5 Radical Smiles: Miscellaneous Rearrangements6 Conclusions
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Polprasert, Chantana, Chantiya Chanswangphuwana, Weerapat Owattanapanich, Smith Kungwankiattichai, Ekarat Rattarittamrong, Thanawat Rattanathammethee, Wasithep Limvorapitak, et al. "Clinical Characteristics and Outcomes of Myeloid Neoplasms with Mecom Rearrangement: Results from a Nationwide Multicenter Study." Blood 142, Supplement 1 (November 28, 2023): 4213. http://dx.doi.org/10.1182/blood-2023-180100.
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MECOM rearrangements are detected in myeloid neoplasms [myelodysplastic neoplasm (MDS) and acute myeloid leukemia (AML)] which are associated with dismal prognosis. Classic MECOM rearrangements include inv(3)(q21q26.2) and t(3;3)(q21;q26) while non-classic subtypes are 3q26.2/ MECOM rearrangement with other partners. Both classic and non-classic rearrangements result in MECOM overexpression which involves in the process of leukemogenesis. Recently, the World Health Organization classification 2022 categorized myeloid neoplasms with these genetic abnormalities as “AML with MECOM rearrangement” regardless of blast count. We aim to explore frequency, clinical characteristics and outcomes including treatment response in this AML subtype among Thai myeloid neoplasms. AML data was collected from a national registry which were conducted by Thai acute leukemia working group. Other than AML with MECOM rearrangements, AML was categorized as favorable, intermediate, and adverse risk groups according to European Leukemia Network 2022. MDS data was collected from a multicenter study group involving 4 medical centers. Other than MDS with MECOM rearrangements, MDS was categorized into 5 risk groups according to R-IPSS score system (very low, low, intermediate, high and very high-risk groups). Myeloid neoplasms with MECOM rearrangements were analyzed among their diseases and grouped together and compared to MDS and AML cohorts. A total of 9 cases of myeloid neoplasms with MECOM rearrangement were detected. Among non-M3 AML cases, there were 6 cases with MECOM rearrangement from 746 non-M3 AML (0.8%) while 3 cases were detected in 163 MDS (1.8%). Seven of 9 cases (78%) were female gender. Five of 9 cases were classic MECOM rearrangement [1 case with inv(3)(q21q26.2) and 4 cases with t(3;3)(q21;q26)] while the other 4 cases were non-classic rearrangements [3 cases with t(3;21)(q26.2;q22) and 1 case with t(3;7)(q26;q21)]. In the AML cohort, AML with MECOM rearrangement showed lower white blood cell, but higher platelet counts compared to other groups (favorable, intermediate, and adverse risk groups) ( Table 1). Among AML cases receiving intensive chemotherapy, MECOM rearrangement subgroup showed lower complete response (CR) rate compared to others favorable, intermediate, and adverse risk groups. (0% vs. 77.3% vs. 37.6% vs. 23.8%; p<0.001). Of note, among 6 AML with MECOM rearrangement, there were 4 patients who received intensive chemotherapy but none of them responded to the treatment. In the MDS cohort, MDS with MECOM rearrangement showed lower hemoglobin and platelet counts compared to other groups ( Table 2). Among 3 MDS with MECOM rearrangement, one patient received azacitidine with investigational drug (sabatolimab/placebo) and achieved complete hematologic response. He eventually progressed after 12 cycles of the treatments and subsequently died. When combining 3 MDS and 6 AML with MECOM rearrangement as one group and compared survival rate with others: survival rate of 9 myeloid neoplasms with MECOM rearrangementis worse than the adverse group of AML and the very high risk group MDS with a 1-year survival rate of 22% ( Figure 1 and 2). In conclusion, myeloid neoplasms with MECOM rearrangements are rare with the frequency of 0.8% in non-M3 AML and 1.8% in MDS. This subtype is more common in female gender. The prognosis of myeloid neoplasms with MECOM rearrangement is dismal with a 1-year survival rate of 16.7% in AML and 6-month survival rate of 33% in MDS. Chemotherapy should be avoided in this subtype due to non-responsiveness, hypomethylating agent showed benefit and can be considered as a bridging treatment before stem cell transplantation. Novel therapy targeting MECOM gene should be further explored to improve outcomes in this AML subtype.
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Margolis, D., M. Yassai, A. Hletko, L. McOlash, and J. Gorski. "Concurrent or sequential delta and beta TCR gene rearrangement during thymocyte development: individual thymi follow distinct pathways." Journal of Immunology 159, no. 2 (July 15, 1997): 529–33. http://dx.doi.org/10.4049/jimmunol.159.2.529.
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Abstract Analysis of TCR rearrangement profiles of well-defined thymocyte populations in a number of individual thymi provides evidence for a new pathway of lineage commitment. In all of the thymi analyzed, alphabeta thymocytes have rearrangements in the delta locus that are enhanced for out-of-frame rearrangements. Thus, not only did alphabeta thymocytes pass through a stage in differentiation that included delta rearrangement, but they also constitute a population that was relatively unsuccessful at these rearrangements. Interestingly, in some thymi, gammadelta thymocytes have out-of-frame beta rearrangements. This represents a novel pathway in which delta and beta rearrangement happens concurrently. In this pathway, selection favors whichever gene is in frame, thus improving the chances of generating useful T cells. In other thymi, gammadelta cells showed no obvious beta gene rearrangement, indicating a sequential rearrangement. Thus, alphabeta/gammadelta lineage commitment can follow at least two distinct pathways in different individuals.
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Zhang, Beibei, Xiaoxian Li, Boying Guo, and Yunfei Du. "Hypervalent iodine reagent-mediated reactions involving rearrangement processes." Chemical Communications 56, no. 91 (2020): 14119–36. http://dx.doi.org/10.1039/d0cc05354f.
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We summarize the developments of hypervalent iodine reagents-mediated reactions involving [1,2]-migration, Hofmann rearrangement, Beckmann rearrangement, ring contraction/expansion, [3,3]-sigmatropic/iodonium-Claisen rearrangement and some miscellaneous rearrangements.
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Annamareddy, Ajay, Bu Wang, Paul M. Voyles, and Dane Morgan. "Distribution of atomic rearrangement vectors in a metallic glass." Journal of Applied Physics 132, no. 19 (November 21, 2022): 195103. http://dx.doi.org/10.1063/5.0125531.
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Short-timescale atomic rearrangements are fundamental to the kinetics of glasses and frequently dominated by one atom moving significantly (a rearrangement), while others relax only modestly. The rates and directions of such rearrangements (or hops) are dominated by the distributions of activation barriers ( Eact) for rearrangement for a single atom and how those distributions vary across the atoms in the system. We have used molecular dynamics simulations of Cu50Zr50 metallic glass below Tg in an isoconfigurational ensemble to catalog the ensemble of rearrangements from thousands of sites. The majority of atoms are strongly caged by their neighbors, but a tiny fraction has a very high propensity for rearrangement, which leads to a power-law variation in the cage-breaking probability for the atoms in the model. In addition, atoms generally have multiple accessible rearrangement vectors, each with its own Eact. However, atoms with lower Eact (or higher rearrangement rates) generally explored fewer possible rearrangement vectors, as the low Eact path is explored far more than others. We discuss how our results influence future modeling efforts to predict the rearrangement vector of a hopping atom.
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Tawa, A., SH Benedict, J. Hara, N. Hozumi, and EW Gelfand. "Rearrangement of the T cell receptor gamma-chain gene in childhood acute lymphoblastic leukemia." Blood 70, no. 6 (December 1, 1987): 1933–39. http://dx.doi.org/10.1182/blood.v70.6.1933.1933.
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Abstract We analyzed rearrangements of the T cell receptor gamma-chain (T gamma) gene as well as rearrangements of the T cell receptor beta-chain (T beta) gene and immunoglobulin heavy-chain (IgH) gene in 68 children with acute lymphoblastic leukemia (ALL). All 15 patients with T cell ALL showed rearrangements of both T beta and T gamma genes. Twenty-four of 53 non-T, non-B ALL patients (45%) showed T gamma gene rearrangements and only 14 of these also showed T beta gene rearrangements. Only a single patient rearranged the T beta gene in the absence of T gamma gene rearrangement. The rearrangement patterns of the T gamma gene in non-T, non-B ALL were quite different from those observed in T cell ALL, as 20 of 23 patients retained at least one germline band of the T gamma gene. In contrast, all T cell ALL patients showed no retention of germline bands. These data indicate that rearrangement of the T gamma gene is not specific for T cell ALL. Further, the results also suggest that T gamma gene rearrangement precedes T beta gene rearrangement. The combined analysis of rearrangement patterns of IgH, T beta, and T gamma genes provides new criteria for defining the cellular origin of leukemic cells and for further delineation of leukemia cell heterogeneity.
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Tawa, A., SH Benedict, J. Hara, N. Hozumi, and EW Gelfand. "Rearrangement of the T cell receptor gamma-chain gene in childhood acute lymphoblastic leukemia." Blood 70, no. 6 (December 1, 1987): 1933–39. http://dx.doi.org/10.1182/blood.v70.6.1933.bloodjournal7061933.
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We analyzed rearrangements of the T cell receptor gamma-chain (T gamma) gene as well as rearrangements of the T cell receptor beta-chain (T beta) gene and immunoglobulin heavy-chain (IgH) gene in 68 children with acute lymphoblastic leukemia (ALL). All 15 patients with T cell ALL showed rearrangements of both T beta and T gamma genes. Twenty-four of 53 non-T, non-B ALL patients (45%) showed T gamma gene rearrangements and only 14 of these also showed T beta gene rearrangements. Only a single patient rearranged the T beta gene in the absence of T gamma gene rearrangement. The rearrangement patterns of the T gamma gene in non-T, non-B ALL were quite different from those observed in T cell ALL, as 20 of 23 patients retained at least one germline band of the T gamma gene. In contrast, all T cell ALL patients showed no retention of germline bands. These data indicate that rearrangement of the T gamma gene is not specific for T cell ALL. Further, the results also suggest that T gamma gene rearrangement precedes T beta gene rearrangement. The combined analysis of rearrangement patterns of IgH, T beta, and T gamma genes provides new criteria for defining the cellular origin of leukemic cells and for further delineation of leukemia cell heterogeneity.
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Aster, J. C., and J. Sklar. "Interallelic V(D)J trans-rearrangement within the beta T cell receptor gene is infrequent and occurs preferentially during attempted D beta to J beta joining." Journal of Experimental Medicine 175, no. 6 (June 1, 1992): 1773–82. http://dx.doi.org/10.1084/jem.175.6.1773.
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Previous work has demonstrated that intergenic V(D)J rearrangement, a process referred to as trans-rearrangement, occurs at an unexpectedly high frequency. These rearrangements generate novel V(D)J combinations which could conceivably have some role in the normal immune system, and since they probably arise through chromosomal rearrangements akin to those associated with lymphoid neoplasia, they may also serve as a model for investigating recombinational events which underlie oncogenesis. In view of the existence of a mechanism that permits relatively frequent intergenic trans-rearrangements, it seems reasonable that interallelic trans-rearrangements involving segments belonging to each of the two alleles of a single antigen receptor gene might also occur. To determine the frequency of such rearrangements, we examined thymocytes of F1 progeny of a cross between SWR mice, which have a deletion spanning 10 of the known V beta segments, and NZW mice, which have a deletion involving all J beta 2 segments. Rearranged TCR-beta genes containing V beta segments from the NZW chromosome and J beta segments from the SWR chromosome were amplified from the DNA of F1 thymocytes with the polymerase chain reaction. Using this approach, we found that such rearrangements are relatively uncommon, being present in about 1 in 10(5) thymocytes, a frequency lower than that of V gamma/J beta intergenic trans-rearrangements. The ratio of conventional cis-rearrangement to interallelic trans-rearrangement for any particular V beta segment appears to be about 10(4):1. The structure of the junctions in all trans-rearrangements analyzed closely resembles conventional cis-rearrangements, indicating involvement of V(D)J recombinase in the ultimate joining event. However, in contrast to cis-rearrangements, a strong bias for inclusion of D beta 1 segments over D beta 2 segments was noted, suggesting that interallelic trans-rearrangement may occur preferentially during attempted D-J joining. J beta 2 segment usage in trans-rearrangements also appeared to differ from that expected from previously studied cis-rearrangements. The results have implications with respect to the events and timing of conventional cis-rearrangement during thymocyte differentiation, and the prevalence of various types of trans-rearrangements.
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Asou, N., M. Matsuoka, T. Hattori, F. Kawano, S. Maeda, K. Shimada, and K. Takatsuki. "T cell gamma gene rearrangements in hematologic neoplasms." Blood 69, no. 3 (March 1, 1987): 968–70. http://dx.doi.org/10.1182/blood.v69.3.968.968.
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Abstract Rearrangements of the T cell gamma (T gamma) gene were studied in primary neoplastic cells from 75 patients with leukemia or lymphoma. T gamma gene rearrangements were observed in 19 of 21 T cell neoplasms; 14 of 21 immature B cell leukemias, including 4 out of 5 patients with rearrangements of both immunoglobulin heavy-chain (JH) and T cell receptor beta chain (T beta) genes; none out of 16 nonlymphoid leukemias. Thus, T gamma gene rearrangement is frequently found in immature B cells and is not always found in T cells showing T beta gene rearrangement, but it is not detected in nonlymphoid cells. Furthermore, T gamma gene rearrangement in cells with the germline configuration of the JH and T beta genes was observed. These results indicate that the detection of T gamma gene rearrangement does not allow a clear assignment to a particular lineage. However, an analysis of T gamma gene rearrangement provides a further potential tool to establish the lymphoid cellular origin and clonality of hematologic neoplasms and identify the normal stages of lymphocyte differentiation.
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Asou, N., M. Matsuoka, T. Hattori, F. Kawano, S. Maeda, K. Shimada, and K. Takatsuki. "T cell gamma gene rearrangements in hematologic neoplasms." Blood 69, no. 3 (March 1, 1987): 968–70. http://dx.doi.org/10.1182/blood.v69.3.968.bloodjournal693968.
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Rearrangements of the T cell gamma (T gamma) gene were studied in primary neoplastic cells from 75 patients with leukemia or lymphoma. T gamma gene rearrangements were observed in 19 of 21 T cell neoplasms; 14 of 21 immature B cell leukemias, including 4 out of 5 patients with rearrangements of both immunoglobulin heavy-chain (JH) and T cell receptor beta chain (T beta) genes; none out of 16 nonlymphoid leukemias. Thus, T gamma gene rearrangement is frequently found in immature B cells and is not always found in T cells showing T beta gene rearrangement, but it is not detected in nonlymphoid cells. Furthermore, T gamma gene rearrangement in cells with the germline configuration of the JH and T beta genes was observed. These results indicate that the detection of T gamma gene rearrangement does not allow a clear assignment to a particular lineage. However, an analysis of T gamma gene rearrangement provides a further potential tool to establish the lymphoid cellular origin and clonality of hematologic neoplasms and identify the normal stages of lymphocyte differentiation.
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Tsuda, S., S. Rieke, Y. Hashimoto, H. Nakauchi, and Y. Takahama. "Il-7 supports D-J but not V-DJ rearrangement of TCR-beta gene in fetal liver progenitor cells." Journal of Immunology 156, no. 9 (May 1, 1996): 3233–42. http://dx.doi.org/10.4049/jimmunol.156.9.3233.
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Abstract The rearrangement of TCR-beta gene, one of the earliest events in T cell development, consists of two consecutive steps: D-J rearrangement and V-DJ rearrangement. The present study examined the signals supporting D-J beta and V-DJ beta rearrangements during early T cell development from progenitor cells that reside in fetal liver. We have found that there is an interval of 1 to 2 days between D-J beta and V-DJ beta rearrangements during the early T cell development from fetal liver progenitor cells in deoxyguanosine-treated thymus lobes. We have also found that IL-7, a cytokine expressed in the subcapsular area of the thymus, can promote D-J beta rearrangement of fetal liver progenitor cells, and that anti-IL-7 and anti-IL-7R Abs inhibit the D-J beta rearrangement and further T cell development of fetal liver progenitor cells in the thymus environment. Interestingly, unlike the thymus environment, IL-7 alone was not capable of supporting V-DJ beta rearrangement in the fetal liver cell cultures. These results indicate that D-J beta rearrangement during fetal liver-derived early T cell development is supported in the thymus by IL-7. Furthermore, the present results demonstrate that IL-7, supporting D-J beta rearrangement, does not promote V-DJ beta rearrangement of fetal liver progenitor cells, suggesting that intrathymic molecules promoting V-DJ beta rearrangement are distinct from IL-7 that supports the D-J beta rearrangement.
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Carico, Zachary Mark, Baojun Zhang, Kingshuk Choudhury, Yuan Zhuang, and Michael S. Krangel. "Mechanisms that diversify an otherwise intrinsically processive Trav-Traj recombination program." Journal of Immunology 198, no. 1_Supplement (May 1, 2017): 202.12. http://dx.doi.org/10.4049/jimmunol.198.supp.202.12.
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Abstract In DP thymocytes, the Tcra locus undergoes multiple rounds of V-J rearrangement in order to generate a functional TCRα chain. While Traj segment usage is strictly ordered from 5′ to 3′ as rearrangement proceeds, it is unclear to what degree Trav usage is also ordered. To test this, we assessed the Trav-Traj combinatorial repertoire in murine DP thymocytes using 5′ RACE followed by paired end sequencing. In 129Sv/J WT thymocytes, we found a clear bias toward proximal-proximal and distal-distal joins, but Trav-Traj pairings were highly diverse, even in primary V-J rearrangement. However, combinatorial diversity was highly constrained in HYα KI thymocytes, in which a fixed primary V-J rearrangement in the endogenous Tcra locus is the starting point for secondary rearrangements. Thus, secondary rearrangement is highly processive through the V and J arrays, but surprising diversity is introduced by primary rearrangement. Tcrd rearrangement precedes Tcra rearrangement in developing thymocytes. In INT1-2KO mice, CTCF site deletion biases Trdv usage toward the most proximal gene segments. These mice, like HYα KI, displayed a substantially constrained Tcra repertoire, with limited diversity of primary rearrangements. Thus, variable truncation of the Trav array by prior Tcrd rearrangement creates diversity in an otherwise highly processive Tcra rearrangement program by imparting combinatorial diversity to primary Tcra rearrangement. This diversification is functionally important, as Trav1-Traj33 pairing and MAIT cell abundance are substantially reduced in HYα and INT1-2KO mice.
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Moore, B. B., and K. Meek. "Recombination potential of the human DIR elements." Journal of Immunology 154, no. 5 (March 1, 1995): 2175–87. http://dx.doi.org/10.4049/jimmunol.154.5.2175.
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Abstract The human DIR genes are putative DH elements that are GC rich and are found between DN and DM DH gene segments. The DIR genes each have consensus recombination signal sequences (RSS) that could conceivably generate DIR coding regions of about 126 nucleotides. These RSS should allow for DH-DH rearrangements that do not violate the 12/23 recombination rule. Several Ig CDR3 sequences have been assigned to DIR usage; however, there are frequent gaps and mismatches associated with these assignments. In some instances these CDR3 sequences might be better explained by GC rich N segment addition. This report analyzes the recombination potential of the human DIR elements by PCR. Though DH-JH rearrangement of the DH genes flanking the DIR regions (DM and DN) are easily demonstrated, very little evidence of DIR-JH rearrangement could be documented. Furthermore, in amplifications that should concurrently detect both DH-DIR rearrangements (which maintain the 12/23 recombination rule) and DH-DH rearrangements (which violate the 12/23 recombination rule), DH-DH rearrangements predominate. We conclude that the DIR-associated RSS participate minimally in both DH-DH and DH-JH rearrangement. In addition, we describe several conventional DH-DH rearrangement intermediates, demonstrating unequivocally that this phenomena occurs during human Ig rearrangement.
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Williams, ME, DJ Jr Innes, MJ Borowitz, MA Lovell, SH Swerdlow, PE Hurtubise, RK Brynes, WC Chan, GE Jr Byrne, and CC Whitcomb. "Immunoglobulin and T cell receptor gene rearrangements in human lymphoma and leukemia." Blood 69, no. 1 (January 1, 1987): 79–86. http://dx.doi.org/10.1182/blood.v69.1.79.79.
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Abstract DNA samples from blood leukocytes or tumor biopsies of 45 patients with phenotypic B or T cell neoplasms were analyzed for rearrangements of the immunoglobulin (Ig) or T cell receptor (TCR) genes by Southern blot hybridization analysis. Rearrangements of the Ig heavy chain joining region genes (JH) were present in DNA from each of 28 B cell lymphomas and leukemias; 14 of 21 of these tumors also had rearrangements of the Ig kappa light chain joining (JK) or deleting element (KDel) genes. Conversely, 16 of 17 T cell lymphomas and leukemias had rearranged TCR beta chain genes. One B cell and one T cell tumor had rearrangements of both Ig and TCR genes. There was a strong correlation between the rearrangements of specific genes and the immunophenotype of the tumor: JH rearrangement without TCR beta chain rearrangement occurred only in B cell tumors; TCR beta chain rearrangement with or without JH rearrangement occurred only in T cell tumors, with one exception; and JK and KDel rearrangements were found only in B cell tumors. Thus, rearrangements of the Ig heavy and light chain genes and the TCR beta chain genes were found to be highly sensitive markers of monoclonal human lymphomas and lymphoid leukemias, with the type of gene rearrangements well correlated with the cell lineage of these neoplasms.
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Williams, ME, DJ Jr Innes, MJ Borowitz, MA Lovell, SH Swerdlow, PE Hurtubise, RK Brynes, WC Chan, GE Jr Byrne, and CC Whitcomb. "Immunoglobulin and T cell receptor gene rearrangements in human lymphoma and leukemia." Blood 69, no. 1 (January 1, 1987): 79–86. http://dx.doi.org/10.1182/blood.v69.1.79.bloodjournal69179.
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DNA samples from blood leukocytes or tumor biopsies of 45 patients with phenotypic B or T cell neoplasms were analyzed for rearrangements of the immunoglobulin (Ig) or T cell receptor (TCR) genes by Southern blot hybridization analysis. Rearrangements of the Ig heavy chain joining region genes (JH) were present in DNA from each of 28 B cell lymphomas and leukemias; 14 of 21 of these tumors also had rearrangements of the Ig kappa light chain joining (JK) or deleting element (KDel) genes. Conversely, 16 of 17 T cell lymphomas and leukemias had rearranged TCR beta chain genes. One B cell and one T cell tumor had rearrangements of both Ig and TCR genes. There was a strong correlation between the rearrangements of specific genes and the immunophenotype of the tumor: JH rearrangement without TCR beta chain rearrangement occurred only in B cell tumors; TCR beta chain rearrangement with or without JH rearrangement occurred only in T cell tumors, with one exception; and JK and KDel rearrangements were found only in B cell tumors. Thus, rearrangements of the Ig heavy and light chain genes and the TCR beta chain genes were found to be highly sensitive markers of monoclonal human lymphomas and lymphoid leukemias, with the type of gene rearrangements well correlated with the cell lineage of these neoplasms.
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Tunyaplin, C., and K. L. Knight. "IgH gene rearrangements on the unexpressed allele in rabbit B cells." Journal of Immunology 158, no. 10 (May 15, 1997): 4805–11. http://dx.doi.org/10.4049/jimmunol.158.10.4805.
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Abstract VDJ genes are assembled in two sequential DNA recombination steps, rearrangement of D and J(H) gene segments followed by rearrangement of a V(H) gene segment. In mouse and human, VDJ gene rearrangements occur in a regulated step in which D rearranges to J(H) on both alleles before V(H) rearranges to DJ. To determine how VDJ gene rearrangements are regulated in the rabbit, we studied the IgH gene rearrangements in rabbit B cells by examining the gene rearrangement on the unexpressed allele in rabbit hybridomas. By Southern blot analysis with probes from the J(H) and 3'V(H)1 regions, we found that approximately 50% of the hybridomas had DJ gene rearrangements on the unexpressed allele, whereas the remaining 50% did not rearrange either J(H) or V(H) genes. Unexpectedly, we found a VD gene rearrangement on the unexpressed allele of a rabbit B cell line, so we PCR-amplified the VD gene rearrangements from splenocyte DNA and found a few VD gene rearrangements in normal B cells as well. The data taken together show that IgH gene rearrangements in rabbit B cells are regulated differently than those in the mouse, and we hypothesize that in some B cells, VDJ gene rearrangements proceed through a VD intermediate rather than through a DJ intermediate.
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Capello, Daniela, Michaela Cerri, Eva Berra, Davide Rossi, Enrica Morra, Giuliana Muti, Marco Paulli, and Gianluca Gaidano. "The Pattern of Immunoglobulin Variable Genes Indicates That Most Post-Transplant Lymphoproliferative Disorders Derive from B-Cells That Have Failed the Germinal Center Reaction." Blood 104, no. 11 (November 16, 2004): 702. http://dx.doi.org/10.1182/blood.v104.11.702.702.
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Abstract Monoclonal posttransplant lymphoproliferative disorders (PTLD) comprise polymorphic PTLD (P-PTLD), diffuse large B cell lymphoma (DLBCL) and Burkitt/Burkitt-like lymphoma (BL/BLL). Recent studies have elucidated the germinal center-origin (GC) of PTLD, yet a detailed analysis of IgVH and IgVL chain genes is lacking. We investigated 54 PTLD, including 16 P-PTLD, 35 DLBCL and 3 BL/BLL for usage, mutation frequency and mutation pattern of clonal IgVH and IgVL rearrangements. A functional IgVH rearrangement was identified in 47/54 (87.0%) cases. Four cases yeilded only an out of frame IgVH rearrangement or a rearrangement rendered nonfunctional by crippling mutations. Three cases showed hybrid Ig VDJ rearrangements: two cases with a V-V fusion rearrangement and one case with a J-J fusion rearrangement, suggesting a failed attempt of heavy chain receptor revision in GC reaction. Despite extensive investigation by multiple PCR strategies, a functional IgVL rearrangement was found in only 25/54 (46.3%) cases. Eleven out of 25 (44.0%) cases harbored IgV kappa rearrangements and 12/25 (48.0%) cases harbored functional IgV lambda rearrangements. Two cases showed the presence of both IgV kappa and IgV lambda functional rearrangements. Among PTLD carrying solely nonfunctional IgVL rearrangements, 7/54 (13.0%) cases showed a crippled rearrangement and 11/54 (20.4%) cases harbored only an out of frame and/or inactivated IgV kappa gene. Inactivation occurred by rearrangement involving the kappa-deleting element (KDE). In 11/54 (20.4%) cases, no IgVL rearrangement was identified. Overall, only 23/54 (42.6%) PTLD displayed both a functional IgVH and a functional IgVL rearrangement. Analysis of somatic hypermutation showed the presence of somatically hypermutated IgVH and/or IgVL genes in 45/54 PTLD (83.3%). Conversely, IgV rearrangements of 9/54 (16.6%) PTLD were in germline configuration, suggesting a derivation from B-cells that have not experienced the GC-reaction. Among mutated cases, the average mutation frequency was 8.83% (median 8.43%, range 2.10%–24.1%) for IgVH genes and 7.37% (median 6.71%, range 2.30%–26.0%) for IgVL genes. Thirty-two cases (71.1%) showed highly mutated (mutation frequency >6%) IgVH and/or IgVL genes, a condition that, in normal B-cell, results in lower affinity for antigen and apoptosis. Analysis of the distribution of replacement and silent mutations in functional IgVH and/or IgVL sequences showed tendency to conserve FR sequences and maintain antigen binding in 20/34 (58.8%) cases. Selection for high affinity antigen binding occurred in 14/34 (41.2%) cases. Our data suggest that most PTLD arise from B-cells that have experienced the GC-reaction and frequently display impaired B-cell receptors (BCR). Since a functional receptor is required for normal B-cell survival during GC transit, PTLD development may implicate rescue from apoptosis and expansion of B-cells that have failed the GC-reaction. Notably, virtually all PTLD with nonfunctional IgVH and/or IgVL rearrangements carried EBV infection, which may promote cell survival.
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Zhang, Lei, Mengjie Hu, and Bo Peng. "[3,3]- and [5,5]-Sigmatropic Rearrangements of Aryl Sulfoxides Using An ‘Assembly/Deprotonation’ Technology." Synlett 30, no. 20 (October 17, 2019): 2203–8. http://dx.doi.org/10.1055/s-0039-1690212.
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The redox-neutral ortho-functionalizations of aryl/heteroaryl sulfoxides via interrupted Pummerer processes have been greatly advanced since its discovery by Kita and Padwa in the early 2000s. In this context, we recently developed an ortho-cyanoalkylation of aryl sulfoxides with alkyl nitriles using an ‘assembly/deprotonation’ protocol. The success of the reaction hinges on the independent control of the electrophilic assembly of both coupling partners and subsequent deprotonation of the in situ generated imine sulfonium intermediates. Further [3,3]-sigmatropic rearrangement of the in situ formed ketenimine sulfonium species furnishes ortho-cyanoalkylated aryl sulfides. More recently, we also applied the ‘assembly/deprotonation’ strategy for the development of the [5,5]-sigmatropic rearrangement of aryl sulfoxides with allyl nitriles that allows for para-cyanoalkylation of aryl sulfoxides. The development of these two reactions is described in this Synpacts article.1 Background2 [3,3]-Sigmatropic Rearrangement3 [5,5]-Sigmatropic Rearrangement4 Conclusion
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Yadav, Priya, Shilpa Yadav, Asha Gurjar, and Raj K. Bansal. "Cope Rearrangement in Bicyclo[5.1.0]octa-2,5-diene and its Mono- and Di-Hetero Analogues: A DFT Study." Australian Journal of Chemistry 70, no. 6 (2017): 683. http://dx.doi.org/10.1071/ch16488.
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The Cope rearrangements of bicyclo[5.1.0]octa-2,5-diene and its 4-hetero-(aza/oxa/phospha) and 4,8-dihetero analogues were investigated using density functional theory at the B3LYP/6–31+G* level in gas phase. The rearrangements of bicyclo[5.1.0]octa-2,5-diene and its symmetrical 4,8-dihetero analogues followed a concerted mechanism involving synchronous transition states. In other cases, although a concerted mechanism was observed, asynchronous transition states were involved. In the case of bicyclo[5.1.0]octa-2,5-diene, a degenerate Cope rearrangement was expected to occur at room temperature (25°C) due to a low free activation energy (ΔG‡ = 14.46 kcal mol–1). However, under similar conditions, the rearrangement of 4,8-dioxabicyclo[5.1.0]octa-2,5-diene was much slower (ΔG‡ = 23.85 kcal mol–1) and the 4,8-diaza- and diphospha analogues did not undergo Cope rearrangement. The Cope rearrangements of 4-phospha-, 8-aza-, 8-aza-4-oxa-, 8-aza-4-phospha-, and 8-oxa-4-phospha-bicyclo[5.1.0]octa-2,5-dienes were exergonic and were expected to occur spontaneously to form the corresponding products. In contrast, rearrangement of 8-oxabicyclo[5.1.0]octa-2,5-diene, though exergonic, was accompanied by a decrease in entropy, due to which Cope rearrangement would occur much more slowly and a mixture of both valence isomers would be formed. The Cope rearrangements of 4-aza-, 4-oxa-, 4-aza-8-oxa-, 8-phospha-, 4-aza-8-phospha-, 4-oxa-8-phospha-, and 4,8-diphospha-bicyclo[5.1.0]octa-2,5-dienes were endergonic; consequently either no Cope rearrangement would take place or it would occur sluggishly.
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Thompson, S. D., J. Pelkonen, and J. L. Hurwitz. "First T cell receptor alpha gene rearrangements during T cell ontogeny skew to the 5' region of the J alpha locus." Journal of Immunology 145, no. 7 (October 1, 1990): 2347–52. http://dx.doi.org/10.4049/jimmunol.145.7.2347.
Full textAbstract:
Abstract Fetal, neonatal, and early postnatal thymi were assessed for TCR J alpha gene rearrangements. Gene probes spanning the distance from 5' to 3' regions of the J alpha locus were used to determine the approximate location of gene rearrangements within hybridomas representing each of the early thymocyte populations. The predominant location of rearrangements was within the 5' region of the J alpha locus. Among the several cells in which rearrangements were found on only one chromosome, the one rearrangements was always in the 5' region. When two rearrangements were found, the rearrangements on homologous chromosomes were usually in the same region. The overall pattern among thymocytes was in great contrast to that previously observed among hybridomas derived from stimulated adult spleen cells within which rearrangements fell mostly to the 3' side of the alpha-locus. Results reveal the nonrandom nature of the TCR-alpha gene rearrangement event and may reflect an incidence of multiple V-J alpha joining events on each chromosome during T cell development in vivo. Due to the fact that most mature cells bear two J alpha joins, the allelic exclusion of alpha-chains cannot be explained by a mechanism whereby a functional rearrangement on one chromosome inhibits subsequent rearrangement on the second. Instead allelic exclusion may rely on a low frequency of productive vs nonproductive rearrangement events and an incompatibility between multiple alpha- and beta-protein pairs.
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Steenbergen, EJ, OJ Verhagen, EF van Leeuwen, AE von dem Borne, and CE van der Schoot. "Distinct ongoing Ig heavy chain rearrangement processes in childhood B- precursor acute lymphoblastic leukemia." Blood 82, no. 2 (July 15, 1993): 581–89. http://dx.doi.org/10.1182/blood.v82.2.581.581.
Full textAbstract:
Abstract Acute lymphoblastic leukemia (ALL) is thought to arise from the clonal expansion of a single transformed precursor cell. However, an oligoclonal Ig heavy chain (IgH) rearrangement pattern has been observed in 30% of ALL patients and was shown to be the result of ongoing rearrangement events. The extent and nature of these ongoing rearrangement processes in individual patients has so far remained obscure. We performed a detailed analysis of leukemic VHDJH rearrangements in three children with B-precursor ALL at diagnosis and one B-lymphoid blast crisis of a child with Ph+ chronic myeloid leukemia at diagnosis and relapse. The children were selected because they presented with multiple IgH rearrangements on Southern blot analysis. Polymerase chain reaction analysis of leukemic cells from two B-precursor ALL patients showed exclusively two groups of related sequences resulting from VH gene replacement events. Most VH gene replacements involved 3′ located acceptor VH genes. Analysis of cells from the other B-precursor ALL patient showed exclusively related sequences as a result of VH gene joinings to a pre-existing DJH rearrangement. In the B-lymphoid blast crisis, a single germline precursor cell had generated multiple unrelated rearrangements and additional groups of related rearrangements resulting from VH to DJH joinings. Direct proof for the VH to DJH joining mechanism was obtained by amplification of the expected preexisting DJH rearrangements. Our findings suggest that the pattern of ongoing rearrangements in an individual patient reflects the IgH rearrangement status of the precursor cell at the time of malignant transformation. Sequence analysis of VHDJH rearrangements at diagnosis may therefore allow a prediction of the reliability of complementarity determining region 3 probes for the detection of minimal residual disease.
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Steenbergen, EJ, OJ Verhagen, EF van Leeuwen, AE von dem Borne, and CE van der Schoot. "Distinct ongoing Ig heavy chain rearrangement processes in childhood B- precursor acute lymphoblastic leukemia." Blood 82, no. 2 (July 15, 1993): 581–89. http://dx.doi.org/10.1182/blood.v82.2.581.bloodjournal822581.
Full textAbstract:
Acute lymphoblastic leukemia (ALL) is thought to arise from the clonal expansion of a single transformed precursor cell. However, an oligoclonal Ig heavy chain (IgH) rearrangement pattern has been observed in 30% of ALL patients and was shown to be the result of ongoing rearrangement events. The extent and nature of these ongoing rearrangement processes in individual patients has so far remained obscure. We performed a detailed analysis of leukemic VHDJH rearrangements in three children with B-precursor ALL at diagnosis and one B-lymphoid blast crisis of a child with Ph+ chronic myeloid leukemia at diagnosis and relapse. The children were selected because they presented with multiple IgH rearrangements on Southern blot analysis. Polymerase chain reaction analysis of leukemic cells from two B-precursor ALL patients showed exclusively two groups of related sequences resulting from VH gene replacement events. Most VH gene replacements involved 3′ located acceptor VH genes. Analysis of cells from the other B-precursor ALL patient showed exclusively related sequences as a result of VH gene joinings to a pre-existing DJH rearrangement. In the B-lymphoid blast crisis, a single germline precursor cell had generated multiple unrelated rearrangements and additional groups of related rearrangements resulting from VH to DJH joinings. Direct proof for the VH to DJH joining mechanism was obtained by amplification of the expected preexisting DJH rearrangements. Our findings suggest that the pattern of ongoing rearrangements in an individual patient reflects the IgH rearrangement status of the precursor cell at the time of malignant transformation. Sequence analysis of VHDJH rearrangements at diagnosis may therefore allow a prediction of the reliability of complementarity determining region 3 probes for the detection of minimal residual disease.
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Feddersen, R. M., D. J. Martin, and B. G. Van Ness. "The frequency of multiple recombination events occurring at the human Ig kappa L chain locus." Journal of Immunology 144, no. 3 (February 1, 1990): 1088–93. http://dx.doi.org/10.4049/jimmunol.144.3.1088.
Full textAbstract:
Abstract Products of Ig kappa L chain gene rearrangement in a variety of human B cell samples were investigated by sequential Southern blot hybridization analysis. By application of four region-specific probes (C kappa, J kappa, U' kappa and kappa de) a complete spectrum of kappa rearrangements, including both predicted and novel products, were detected. Nearly 30% of the products detected reflect multiple recombination of the kappa locus. The kappa-deleting element was responsible for 70% of the multiple rearrangements that were detected. Interestingly, eight kappa-expressing samples exhibited rearrangement of the kappa-deleting element. The remaining multiple recombination products were characteristic of double V kappa-J kappa rearrangement. This frequency reveals that secondary V-J rearrangement may significantly contribute to the expression of kappa L chains in humans.
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Graninger, W. B., P. L. Goldman, C. C. Morton, S. J. O'Brien, and S. J. Korsmeyer. "The kappa-deleting element. Germline and rearranged, duplicated and dispersed forms." Journal of Experimental Medicine 167, no. 2 (February 1, 1988): 488–501. http://dx.doi.org/10.1084/jem.167.2.488.
Full textAbstract:
Human light chain genes are used in a kappa before lambda order. Accompanying this hierarchy is the rearrangement of a kappa-deleting element (Kde) which eliminates the kappa locus before lambda gene rearrangement. In approximately 60% of rearrangements the Kde recombines at a conserved heptamer within the J kappa-C kappa intron. We demonstrated that aberrant V/J rearrangements possessing apparent "N" nucleotides existed 5' to the J kappa-Kde rearrangements. This suggests that the Kde may selectively eliminate nonfunctional V/J alleles. A kappa-producing cell that displayed the unusual finding of lambda gene rearrangement demonstrated a rearranged Kde. This rearrangement was a V kappa/Kde recombination and the heptamer-11 bp spacer-nonamer flanking the V kappa is the target site of the Kde 40% of the time. The mouse possesses a counterpart to the Kde (recombining sequence [RS]) and the highly conserved regions surround the heptamer-spacer-nonamer signals. No complete protein product was predicted from the germline Kde near its break-point and no consistent fusion product was predicted from either the V/Kde or V/J-Kde rearrangements. A distal portion of the Kde is duplicated and is present at 2q11 as well as 2p11. The evolutionary conservation of the kappa-elimination event, the duplication and maintenance of the Kde indicates that it has a function. A portion of the Kde may still prove to encode a trans-acting factor that directly affects lambda rearrangement. A certain role for the Kde is its site-specific rearrangement, which destroys ineffective kappa genes and sets the stage for lambda gene utilization.
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Ge, Xinyu, Haoming Zang, Xiaoyun Ye, Lang Peng, Beixin Wang, Gang Lian, and Changhai Sun. "Comparative Mitogenomic Analyses of Hydropsychidae Revealing the Novel Rearrangement of Protein-Coding Gene and tRNA (Trichoptera: Annulipalpia)." Insects 13, no. 9 (August 23, 2022): 759. http://dx.doi.org/10.3390/insects13090759.
Full textAbstract:
Gene rearrangement of the mitochondrial genome of insects, especially the rearrangement of protein-coding genes, has long been a hot topic for entomologists. Although mitochondrial gene rearrangement is common within Annulipalpia, protein-coding gene rearrangement is relatively rare. As the largest family in Annulipalpia, the available mitogenomes from Hydropsychidae Curtis, 1835 are scarce, and thus restrict our interpretation of the mitogenome characteristic. In this study, we obtained 19 novel mitogenomes of Hydropsychidae, of which the mitogenomes of the genus Arctopsyche are published for the first time. Coupled with published hydropsychid mitogenome, we analyzed the nucleotide composition evolutionary rates and gene rearrangements of the mitogenomes among subfamilies. As a result, we found two novel gene rearrangement patterns within Hydropsychidae, including rearrangement of protein-coding genes. Meanwhile, our results consider that the protein-coding gene arrangement of Potamyia can be interpreted by the tandem duplication/random loss (TDRL) model. In addition, the phylogenetic relationships within Hydropsychidae constructed by two strategies (Bayesian inference and maximum likelihood) strongly support the monophyly of Arctopscychinae, Diplectroninae, Hydropsychinae, and Macronematinae. Our study provides new insights into the mechanisms and patterns of mitogenome rearrangements in Hydropsychidae.
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Piper, Hannah, Samuel Litwin, and Ramit Mehr. "Models for Antigen Receptor Gene Rearrangement. II. Multiple Rearrangement in the TCR: Allelic Exclusion or Inclusion?" Journal of Immunology 163, no. 4 (August 15, 1999): 1799–808. http://dx.doi.org/10.4049/jimmunol.163.4.1799.
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Abstract This series of papers addresses the effects of continuous Ag receptor gene rearrangement in lymphocytes on allelic exclusion. The previous paper discussed light chain gene rearrangement and receptor editing in B cells, and showed that these processes are ordered on three different levels. This order, combined with the constraints imposed by a strong negative selection, was shown to lead to effective allelic exclusion. In the present paper, we discuss rearrangement of TCR genes. In the TCR α-chain, allelic inclusion may be the rule rather than the exception. Several previous models, which attempted to explain experimental observations, such as the fractions of cells containing two productive TCRα rearrangements, did not sufficiently account for TCR gene organization, which limits secondary rearrangement, and for the effects of subsequent thymic selection. We present here a detailed, comprehensive computer simulation of TCR gene rearrangement, incorporating the interaction of this process with other aspects of lymphocyte development, including cell division, selection, cell death, and maturation. Our model shows how the observed fraction of T cells containing productive TCRα rearrangements on both alleles can be explained by the parameters of thymic selection imposed over a random rearrangement process.
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Vanjari, Neelam, Guilin Tang, Gokce A. Toruner, Wei Wang, Beenu Thakral, Ming Zhao, Bhavana J. Dave, Joseph D. Khoury, L. Jeffrey Medeiros, and Zhenya Tang. "Optical Genome Mapping Helps to Identify BCR::JAK2 Rearrangement Arising from Cryptic Complex Chromosomal Aberrations: A Case Report and Literature Review." Genes 14, no. 12 (December 8, 2023): 2188. http://dx.doi.org/10.3390/genes14122188.
Full textAbstract:
We report a case of myeloproliferative neoplasm, not otherwise specified (MPN-NOS)-transformed AML with BCR::JAK2 rearrangement. Chromosomal analysis indicated a simple abnormal karyotype 46,XY,t(7;17)(q21;q24),t(9;22)(p24;q11.2). Fluorescence in situ hybridization (FISH) using a BCR/ABL1/ASS1 probe set suggested a possible BCR rearrangement and a reflex JAK2 breakapart probe indicated JAK2 rearrangement, most likely partnered with BCR. Optical genome mapping (OGM) analysis confirmed BCR::JAK2 derived through an inv(9)(p24p13) after a t(9;22)(p13;q11.2) in this case. Due to the complexity of chromosomal aberrations, disruption and/or rearrangement of other genes such as KIF24::BCR, JAK2::KIF24/UBAP1, and CDK6:SOX9 were also identified by OGM. Although the functionality and clinical importance of these novel rearrangements were unknown, disruption of these genes might be associated with a poorer response to chemotherapy and disease progression. We also reviewed all cases with BCR::JAK2 rearrangement reported in the literature. In conclusion, a suspected t(9;22)/BCR::JAK2 rearrangement warrants further characterization with genomic assays such as OGM, whole chromosome sequencing, and RNA sequencing to explore other gene disruptions and/or rearrangements.
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Breit, T. M., M. C. Verschuren, I. L. Wolvers-Tettero, E. J. Van Gastel-Mol, K. Hählen, and J. J. van Dongen. "Human T cell leukemias with continuous V(D)J recombinase activity for TCR-delta gene deletion." Journal of Immunology 159, no. 9 (November 1, 1997): 4341–49. http://dx.doi.org/10.4049/jimmunol.159.9.4341.
Full textAbstract:
Abstract The so-called TCR-delta-deleting elements, deltaRec and psiJ alpha, flank the major part of the TCR-delta gene complex. By rearranging to each other, the deltaRec and psiJ alpha gene segments delete the TCR-delta gene complex and prepare the allele for subsequent TCR-alpha rearrangement. This intermediate rearrangement is thought to be a specific rearrangement event. In our studies on TCR-delta deletion mechanisms, we identified several T cell acute lymphoblastic leukemias (T-ALL) with continuous activity of the deltaRec-psiJ alpha rearrangement process. Extensive Southern blot, PCR, and sequencing analyses on the coding joints as well as the signal joints of the deltaRec-psiJ alpha rearrangements in these patients allowed us to prove that this continuous rearrangement activity occurred in the leukemic cells and that these cells, therefore, represent a polyclonal subpopulation within the otherwise monoclonal T-ALL. In additional studies, we also identified a T cell line (DND41) with continuous activity of the deltaRec-psiJ alpha rearrangement process. Our data suggest that the ongoing deltaRec-psiJ alpha gene rearrangements predominantly occur in T cells that cannot express a functional TCR-gammadelta, due to biallelic out-of-frame TCR-delta and/or TCR-gamma gene rearrangements. The described T-ALL and the T cell line can serve as an experimental model in further studies on the regulatory elements involved in the specific deletion of the TCR-delta gene complex.
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Lawler, A. M., J. F. Kearney, M. Kuehl, and P. J. Gearhart. "Early rearrangements of genes encoding murine immunoglobulin kappa chains, unlike genes encoding heavy chains, use variable gene segments dispersed throughout the locus." Proceedings of the National Academy of Sciences 86, no. 17 (September 1989): 6744–47. http://dx.doi.org/10.1073/pnas.86.17.6744.
Full textAbstract:
Immunoglobulin heavy-chain variable region (TH) gene segments located closest to the joining (JH) gene segments are preferentially rearranged during ontogeny, indicating that chromosomal position influences the frequency of rearrangement. In addition, certain VH gene segments are repeatedly rearranged, suggesting that the DNA sequence or structure surrounding these segments may increase the probability of rearrangement. To determine whether there is similar based rearrangement of kappa variable (V kappa) gene segments, 25 rearrangements were sequenced from murine fetal and neonatal B-cell hybridomas and from subclones of a pre-B cell line that rearranged V kappa genes during in vitro culture. Four gene segments were isolated twice and one gene segment was isolated three times, suggesting that the process that targets individual variable gene segments for repeated rearrangement operates on both the VH and V kappa loci. Based on a current map of the V kappa locus, the rearranged gene segments belong to nine families that are dispersed throughout the locus. Thus, in these cell types, V kappa rearrangements use germ-line gene segments located across the entire locus, whereas the corresponding VH rearrangements use gene segments proximal to the JH gene segments. Heterogeneity of V kappa rearrangements would add diversity to the biased pool of VH rearrangements, producing a broad repertoire of antibodies early in development.
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Liu, Feifei, Lindsay G. Cowell, Emily Heikamp, and Garnett Kelsoe. "Antigen-independent secondary Igκ rearrangement in B-cell development – implications for receptor editing (B39)." Journal of Immunology 178, no. 1_Supplement (April 1, 2007): LB8. http://dx.doi.org/10.4049/jimmunol.178.supp.b39.
Full textAbstract:
Abstract Receptor editing by secondary Vκ-to-Jκ rearrangements is thought to be driven by reactivity to self. However, the evidence supporting antigen-driven editing is open to other interpretations; analysis of Igκ excision circles from birds and mice indicates continuing V(D)J recombination in cis after both functional (F) and non-functional (nF) rearrangements. We have determined the extent and nature of secondary Vκ-to-Jκ rearrangements by analyzing their intermediate cleavage products in the 103/Bcl2 cell line and in purified compartments of developing B cells from normal, Jκ−/+, and IgH transgenic mice. In all cases, we find that the ratio of F:nF VκJκ joints replaced by secondary rearrangement is approximately 1:2, the ratio expected for rearrangement without feedback of any kind. Secondary rearrangement is initiated in small pre-B cells and in BrdU pulse-labeling studies, we detected no evidence for immature to pre-B “retrograde” differentiation. Thus, “receptor editing” occurs in B cells that do not express surface Ig. Significantly, in 3H9 IgH transgenic mice, replacement rearrangements exhibited F:nF ratios of 1:2, regardless of whether the initial rearrangements were permissive or non-permissive for autoreactivity. Our results demonstrate continuing Vκ-to-Jκ rearrangement on a single chromosome without feedback and imply that “receptor editing” is an illusion of antigen-driven selection.
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Van Houten, N., and G. Haughton. "Simultaneously arising Ly-1(CD5) B cell lymphomas have identical expressed IgH and kappa-genes but different nonproductive heavy chain rearrangements." Journal of Immunology 144, no. 2 (January 15, 1990): 745–51. http://dx.doi.org/10.4049/jimmunol.144.2.745.
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Abstract A group of CD5(Ly-1) B cell lymphomas are described. They were derived from mice which received a common pool of syngeneic mouse spleen cells. Southern blot analysis revealed that the lymphomas exhibited an unusual set of Ig gene rearrangements. Six lymphomas analyzed had either of two rearrangement patterns. EcoRI restriction digests of tumor DNA probed for rearrangements in the JH region, resulted in restriction fragments of 4.7 and 5.6 kb or of 4.7 and 8.5 kb. Each had an identical HindIII restriction fragment identified when probed for kappa gene rearrangements. Inasmuch as several B cell lymphomas from mice receiving a common pool of spleen cells had identical kappa-rearrangements and one identical IgH rearrangement, it was important to determine the DNA sequence of expressed IgH and kappa-genes. Each tumor was found to have identical nucleotide sequences of VH-DH-JH and VK-JK. The nonproductive IgH rearrangements each consisted of incomplete DH-JH rearrangements. The 8.5-kb EcoRI fragment was generated from a DFL16 gene segment rearranged into JH3, and the 5.6-kb fragment was generated from DQ52 rearranged into JH)1. We conclude that these Ly-1 B tumors are most likely derived from a single clone of cells which underwent a secondary rearrangement on the nonproductive allele after kappa-rearrangement had occurred. The alternate possibility of independently arising lymphomas with identical expressed VH and VK sequences is discussed.
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Asou, N., T. Hattori, M. Matsuoka, F. Kawano, and K. Takatsuki. "Rearrangements of T-cell antigen receptor delta chain gene in hematologic neoplasms." Blood 74, no. 8 (December 1, 1989): 2707–12. http://dx.doi.org/10.1182/blood.v74.8.2707.2707.
Full textAbstract:
Abstract Rearrangements of the T-cell antigen receptor (TCR) delta chain gene were studied in primary neoplastic cells from 137 patients with leukemia or lymphoma. TCR delta gene rearrangements or deletions were observed in all 50 T-cell neoplasms: 5 of 8 CD3- T-cell neoplasms showed rearrangements, whereas biallelic deletion of TCR delta gene was the most common pattern in CD3+ T-cell neoplasm (39 of 42 patients). Rearrangements of TCR delta gene were also detected in 23 of 40 immature B-cell leukemias, including 22 of 25 patients with rearrangements of TCR gamma gene, 2 of 17 mature B-cell neoplasms, and 3 of 30 myeloid leukemias. Thus, TCR delta gene rearrangement or deletion is always found in T-cell neoplasms and is frequently found in immature B-cell leukemias associated with TCR gamma gene rearrangement. Furthermore, TCR delta gene rearrangements associated with the germline configuration of the TCR beta, gamma, and immunoglobulin heavy chain genes were observed in two immature T-cell leukemias, suggesting that TCR delta gene rearrangements precede TCR gamma and beta gene rearrangements. These results indicate that an analysis of TCR delta gene rearrangement provides potential tools to establish the clonality of immature T-cell neoplasms and to identify the normal stages of lymphocyte differentiation.
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Asou, N., T. Hattori, M. Matsuoka, F. Kawano, and K. Takatsuki. "Rearrangements of T-cell antigen receptor delta chain gene in hematologic neoplasms." Blood 74, no. 8 (December 1, 1989): 2707–12. http://dx.doi.org/10.1182/blood.v74.8.2707.bloodjournal7482707.
Full textAbstract:
Rearrangements of the T-cell antigen receptor (TCR) delta chain gene were studied in primary neoplastic cells from 137 patients with leukemia or lymphoma. TCR delta gene rearrangements or deletions were observed in all 50 T-cell neoplasms: 5 of 8 CD3- T-cell neoplasms showed rearrangements, whereas biallelic deletion of TCR delta gene was the most common pattern in CD3+ T-cell neoplasm (39 of 42 patients). Rearrangements of TCR delta gene were also detected in 23 of 40 immature B-cell leukemias, including 22 of 25 patients with rearrangements of TCR gamma gene, 2 of 17 mature B-cell neoplasms, and 3 of 30 myeloid leukemias. Thus, TCR delta gene rearrangement or deletion is always found in T-cell neoplasms and is frequently found in immature B-cell leukemias associated with TCR gamma gene rearrangement. Furthermore, TCR delta gene rearrangements associated with the germline configuration of the TCR beta, gamma, and immunoglobulin heavy chain genes were observed in two immature T-cell leukemias, suggesting that TCR delta gene rearrangements precede TCR gamma and beta gene rearrangements. These results indicate that an analysis of TCR delta gene rearrangement provides potential tools to establish the clonality of immature T-cell neoplasms and to identify the normal stages of lymphocyte differentiation.
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Schnepf, Nathalie, Claire Deback, Axelle Dehee, Elyanne Gault, Nathalie Parez, and Antoine Garbarg-Chenon. "Rearrangements of Rotavirus Genomic Segment 11 Are Generated during Acute Infection of Immunocompetent Children and Do Not Occur at Random." Journal of Virology 82, no. 7 (January 23, 2008): 3689–96. http://dx.doi.org/10.1128/jvi.01770-07.
Full textAbstract:
ABSTRACT Group A rotaviruses are the main cause of viral gastroenteritis in infants. The viral genome consists of 11 double-stranded RNA (dsRNA) segments. Dysfunction of the viral RNA polymerase can lead to gene rearrangements, which most often consist of partial sequence duplication of a dsRNA segment. Gene rearrangements have been detected in vivo during chronic infection in immunodeficient children or in vitro during passages at a high multiplicity of infection in cell culture, suggesting that these replication conditions lead to selective advantages favoring the recovery of viruses with rearranged genes. During acute rotavirus infection, the replication level is high, but the occurrence of rearrangement events has never been reported. By the use of a reverse transcription-PCR assay specifically designed to detect small numbers of copies of rearranged forms of segment 11 in a high background of its standard counterpart, we detected 12 rearrangement events among 161 cases (7.5%) of acute rotavirus infection in immunocompetent children. Strikingly, in all but one case, rearrangement took place at the same location within the short direct repeat AUGU sequence. For the unique case with a different rearrangement pattern, the rearrangement occurred within the direct repeat ACAAGUC that was specific for this isolate. In conclusion, we report the occurrence of segment 11 rearrangements during acute rotavirus infection in immunocompetent children. We show that under such conditions of infection, the viral RNA polymerase generates rearrangements which occur not at random but within direct repeats which might constitute hot spots for RNA recombination.
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Wang, Zheng, and Jiecheng Chen. "An Odd Rearrangement ofL1(Rn)." Journal of Function Spaces 2014 (2014): 1–11. http://dx.doi.org/10.1155/2014/787840.
Full textAbstract:
We introduce an odd rearrangementf*defined byπ(f)(x)=f*(x)=sgn(x1)f*(νn|x|n),x∈Rn, wheref*is a decreasing rearrangement of the measurable functionf. With the help of this odd rearrangement, we show that for eachf∈L1(Rn), there exists ag∈H1(Rn)such thatdf=dg, wheredfis an distribution function off. Moreover, we study the boundedness of singular integral operators when they are restricted to odd rearrangement ofL1(Rn), and we give some results on Hilbert transform.
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de Villartay, JP, AB Pullman, R. Andrade, E. Tschachler, O. Colamenici, L. Neckers, DI Cohen, and J. Cossman. "Gamma/delta lineage relationship within a consecutive series of human precursor T-cell neoplasms." Blood 74, no. 7 (November 15, 1989): 2508–18. http://dx.doi.org/10.1182/blood.v74.7.2508.2508.
Full textAbstract:
Abstract We analyzed the gene rearrangements associated with the newly described delta T-cell receptor (TCR) gene from a series of 19 consecutive precursor T-cell (lymphoblastic) neoplasms that represent discrete stages surrounding the TCR gene rearrangement process. Significantly, the delta TCR gene showed rearrangement in most (13 of 19) of these T cells, and in addition it was rearranged in two cells displaying no rearrangement for any other TCR gene. Our survey showed three types of delta gene rearrangements associated with cell-surface TCR expression that presumably represent usage of three V delta genes. This analysis demonstrates (1) a major subclass of human precursor T-cell neoplasms belonging to the gamma/delta T-cell receptor-rearranging subtype; (2) a narrow repertoire of human V delta gene usage; and (3) the utility of delta gene rearrangements as a diagnostic clonal marker in precursor T lymphoblastic neoplasms.
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de Villartay, JP, AB Pullman, R. Andrade, E. Tschachler, O. Colamenici, L. Neckers, DI Cohen, and J. Cossman. "Gamma/delta lineage relationship within a consecutive series of human precursor T-cell neoplasms." Blood 74, no. 7 (November 15, 1989): 2508–18. http://dx.doi.org/10.1182/blood.v74.7.2508.bloodjournal7472508.
Full textAbstract:
We analyzed the gene rearrangements associated with the newly described delta T-cell receptor (TCR) gene from a series of 19 consecutive precursor T-cell (lymphoblastic) neoplasms that represent discrete stages surrounding the TCR gene rearrangement process. Significantly, the delta TCR gene showed rearrangement in most (13 of 19) of these T cells, and in addition it was rearranged in two cells displaying no rearrangement for any other TCR gene. Our survey showed three types of delta gene rearrangements associated with cell-surface TCR expression that presumably represent usage of three V delta genes. This analysis demonstrates (1) a major subclass of human precursor T-cell neoplasms belonging to the gamma/delta T-cell receptor-rearranging subtype; (2) a narrow repertoire of human V delta gene usage; and (3) the utility of delta gene rearrangements as a diagnostic clonal marker in precursor T lymphoblastic neoplasms.
38
Carico, Zachary, and Michael Krangel. "The T cell receptor alpha/delta locus adopts distinct contracted conformations during primary and secondary T cell receptor α rearrangement (HEM2P.242)." Journal of Immunology 194, no. 1_Supplement (May 1, 2015): 51.12. http://dx.doi.org/10.4049/jimmunol.194.supp.51.12.
Full textAbstract:
Abstract In DP thymocytes, primary TCRα rearrangements are restricted to proximal Vα segments at the 3’ end of the Tcra/d locus. We have shown that this restricted Vα usage is supported by a 3’ contracted and 5’ decontracted conformation of Tcra/d. Secondary rearrangement, however, generates a far more diverse pool of Vα-Jα pairings. To investigate the structure the 5’ end of the locus might adopt after primary rearrangement, we performed 3D-FISH on Tcra/d alleles engineered to mimic a natural TRAV17-TRAJ57 rearrangement. We found that the artificially rearranged Tcra/d alleles were markedly contracted at the 5’ end relative to unrearranged Tcra/d. Notably, we observed a similar 5’ end contraction of the locus in CTCF-deficient DP thymocytes with unrearranged Tcra/d. This led us to hypothesize that loss of a critical CTCF binding site as a result of primary rearrangement might promote the 5’ end contraction. Knockout of the T early alpha promoter (TEA), but not other CTCF-bound elements in the region deleted by primary rearrangement, resulted in 5’ contraction of Tcra/d. These data suggest that diversity in secondary TCRα rearrangements is supported by contraction of the whole length of Tcra/d, and that CTCF binding by TEA plays a critical role in enforcing a 5’ decontracted conformation for primary rearrangement. Using 4C, we are now working to understand specific changes in long-range DNA contacts between pre- and post-rearrangement alleles.
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Feng, Yi, Leslie Y. Beh, Wei-Jen Chang, and Laura F. Landweber. "SIGAR: Inferring Features of Genome Architecture and DNA Rearrangements by Split-Read Mapping." Genome Biology and Evolution 12, no. 10 (August 13, 2020): 1711–18. http://dx.doi.org/10.1093/gbe/evaa147.
Full textAbstract:
Abstract Ciliates are microbial eukaryotes with distinct somatic and germline genomes. Postzygotic development involves extensive remodeling of the germline genome to form somatic chromosomes. Ciliates therefore offer a valuable model for studying the architecture and evolution of programed genome rearrangements. Current studies usually focus on a few model species, where rearrangement features are annotated by aligning reference germline and somatic genomes. Although many high-quality somatic genomes have been assembled, a high-quality germline genome assembly is difficult to obtain due to its smaller DNA content and abundance of repetitive sequences. To overcome these hurdles, we propose a new pipeline, SIGAR (Split-read Inference of Genome Architecture and Rearrangements) to infer germline genome architecture and rearrangement features without a germline genome assembly, requiring only short DNA sequencing reads. As a proof of principle, 93% of rearrangement junctions identified by SIGAR in the ciliate Oxytricha trifallax were validated by the existing germline assembly. We then applied SIGAR to six diverse ciliate species without germline genome assemblies, including Ichthyophthirius multifilii, a fish pathogen. Despite the high level of somatic DNA contamination in each sample, SIGAR successfully inferred rearrangement junctions, short eliminated sequences, and potential scrambled genes in each species. This pipeline enables pilot surveys or exploration of DNA rearrangements in species with limited DNA material access, thereby providing new insights into the evolution of chromosome rearrangements.
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Lister, Troy, Rolf H. Prager, Michael Tsaconas, and Kerry L. Wilkinson. "On the Thermally Induced Rearrangement of 2-Alkoxypyridines to N-alkylpyridones." Australian Journal of Chemistry 56, no. 9 (2003): 913. http://dx.doi.org/10.1071/ch03044.
Full textAbstract:
Analogues of 2-methoxypyridine undergo rearrangement to N-methylpyridones under flash vacuum pyrolysis (FVP) conditions. Ethoxy derivatives undergo competitive ethyl migration and elimination of ethylene. Analogues of 4-methoxypyridine do not undergo rearrangement under FVP conditions, but demethylation on silica may occur. The ease of rearrangement follows the basicity of the alkoxyhetarene to some extent. The vapour-phase rearrangements have been contrasted to condensed-phase pyrolyses, and a four-centre transition state for the former is supported by computation. The rearrangement allows structural assignment to the two products from the reaction of 2,4-dichloroquinoline with pyrrolidine.
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Dik, Willem A., Karin Pike-Overzet, Floor Weerkamp, Dick de Ridder, Edwin F. E. de Haas, Miranda R. M. Baert, Peter van der Spek, et al. "New insights on human T cell development by quantitative T cell receptor gene rearrangement studies and gene expression profiling." Journal of Experimental Medicine 201, no. 11 (May 31, 2005): 1715–23. http://dx.doi.org/10.1084/jem.20042524.
Full textAbstract:
To gain more insight into initiation and regulation of T cell receptor (TCR) gene rearrangement during human T cell development, we analyzed TCR gene rearrangements by quantitative PCR analysis in nine consecutive T cell developmental stages, including CD34+ lin− cord blood cells as a reference. The same stages were used for gene expression profiling using DNA microarrays. We show that TCR loci rearrange in a highly ordered way (TCRD-TCRG-TCRB-TCRA) and that the initiating Dδ2-Dδ3 rearrangement occurs at the most immature CD34+CD38−CD1a− stage. TCRB rearrangement starts at the CD34+CD38+CD1a− stage and complete in-frame TCRB rearrangements were first detected in the immature single positive stage. TCRB rearrangement data together with the PTCRA (pTα) expression pattern show that human TCRβ-selection occurs at the CD34+CD38+CD1a+ stage. By combining the TCR rearrangement data with gene expression data, we identified candidate factors for the initiation/regulation of TCR recombination. Our data demonstrate that a number of key events occur earlier than assumed previously; therefore, human T cell development is much more similar to murine T cell development than reported before.
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Yumura-Yagi, K., J. Hara, N. Terada, S. Ishihara, A. Tawa, Y. Takihara, E. Champagne, MD Minden, TW Mak, and K. Kawa-Ha. "Analysis of molecular events in leukemic cells arrested at an early stage of T-cell differentiation." Blood 74, no. 6 (November 1, 1989): 2103–11. http://dx.doi.org/10.1182/blood.v74.6.2103.2103.
Full textAbstract:
Abstract We analyzed the rearrangement and expression of T-cell receptor (TCR) genes, including the recently identified TCR delta gene, in 21 patients with T-lineage leukemia/lymphoma. Among 8 patients with CD3-, CD4-, and CD8- (group I), 2 patients showed germline configuration of the TCR delta, gamma, beta, and alpha genes and 1 patient demonstrated only TCR delta gene rearrangement. All nine patients with CD3-, CD4+, and/or CD8+ (group II) showed concomitant rearrangements of the TCR delta, gamma, and beta genes. TCR alpha gene rearrangement was also observed in two patients. Three of four patients with CD3+ (group III) showed rearrangement of the TCR alpha gene with deletion of both alleles or of a single allele of the TCR delta gene. With Northern blot analysis, full-length transcripts of the TCR delta gene were detected in 3 of 15 examined patients. All were restricted to group I or group II. In contrast, full-length transcripts of TCR beta and alpha were observed mainly in samples from groups II and III. Based on these findings, rearrangement of the TCR delta gene may be the earliest event in T-cell differentiation, preceding rearrangements of the other TCR genes.
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Yumura-Yagi, K., J. Hara, N. Terada, S. Ishihara, A. Tawa, Y. Takihara, E. Champagne, MD Minden, TW Mak, and K. Kawa-Ha. "Analysis of molecular events in leukemic cells arrested at an early stage of T-cell differentiation." Blood 74, no. 6 (November 1, 1989): 2103–11. http://dx.doi.org/10.1182/blood.v74.6.2103.bloodjournal7462103.
Full textAbstract:
We analyzed the rearrangement and expression of T-cell receptor (TCR) genes, including the recently identified TCR delta gene, in 21 patients with T-lineage leukemia/lymphoma. Among 8 patients with CD3-, CD4-, and CD8- (group I), 2 patients showed germline configuration of the TCR delta, gamma, beta, and alpha genes and 1 patient demonstrated only TCR delta gene rearrangement. All nine patients with CD3-, CD4+, and/or CD8+ (group II) showed concomitant rearrangements of the TCR delta, gamma, and beta genes. TCR alpha gene rearrangement was also observed in two patients. Three of four patients with CD3+ (group III) showed rearrangement of the TCR alpha gene with deletion of both alleles or of a single allele of the TCR delta gene. With Northern blot analysis, full-length transcripts of the TCR delta gene were detected in 3 of 15 examined patients. All were restricted to group I or group II. In contrast, full-length transcripts of TCR beta and alpha were observed mainly in samples from groups II and III. Based on these findings, rearrangement of the TCR delta gene may be the earliest event in T-cell differentiation, preceding rearrangements of the other TCR genes.
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Kramer, M. H. H., J. Hermans, E. Wijburg, K. Philippo, E. Geelen, J. H. J. M. van Krieken, D. de Jong, E. Maartense, E. Schuuring, and P. M. Kluin. "Clinical Relevance of BCL2, BCL6, and MYC Rearrangements in Diffuse Large B-Cell Lymphoma." Blood 92, no. 9 (November 1, 1998): 3152–62. http://dx.doi.org/10.1182/blood.v92.9.3152.
Full textAbstract:
Abstract Diffuse large B-cell lymphoma (DLCL) is characterized by a marked degree of morphologic and clinical heterogeneity. We studied 156 patients with de novo DLCL for rearrangements of the BCL2, BCL6, and MYC oncogenes by Southern blot analysis and BCL2 protein expression. We related these data to the primary site of presentation, disease stage, and other clinical risk factors. Structural alterations of BCL2, BCL6, and MYC were detected in 25 of 156, 36 of 116, and 10 of 151 patients, respectively. Three cases showed a combination of BCL2 and BCL6 rearrangements, and two cases had a combination of BCL6 and MYC rearrangements. BCL2 rearrangement was found more often in extensive (39%) and primary nodal (17%) lymphomas than in extranodal cases (4%) (P = .003). BCL2 rearrangement was present in none of 40 patients with stage I disease, but in 22% of patients with stage II to IV (P = .006). The presence of BCL2 rearrangements did not significantly affect overall survival (OS) or disease-free survival (DFS). In contrast, high BCL2 protein expression adversely affected both OS (P = .008) and DFS (P = .01). BCL2 protein expression was poorly correlated with BCL2 rearrangement: only 52% of BCL2-rearranged lymphomas and 37% of BCL2-unrearranged cases had high BCL2 protein expression. Rearrangement of BCL6 was found more often in patients with extranodal (36%) and extensive (39%) presentation versus primary nodal disease (28%). No significant correlation was found with disease stage, lymphadenopathy, or bone marrow involvement. DFS and OS were not influenced by BCL6 rearrangements. MYC rearrangements were found in 16% of primary extranodal lymphomas, versus 2% of primary nodal cases (P = .02). In particular, gastrointestinal (GI) lymphomas (5 of 18 cases, 28%) were affected by MYC rearrangements. The distinct biologic behavior of these extranodal lymphomas was reflected by a high complete remission (CR) rate: 7 of 10 patients with MYC rearrangement attained complete remission and 6 responders remained alive for more than 4 years, resulting in a trend for better DFS (P = .07). These data show the complex nature of molecular events in DLCL, which is a reflection of the morphologic and clinical heterogeneity of these lymphomas. However, thus far, these genetic rearrangements fail as prognostic markers. © 1998 by The American Society of Hematology.
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Kramer, M. H. H., J. Hermans, E. Wijburg, K. Philippo, E. Geelen, J. H. J. M. van Krieken, D. de Jong, E. Maartense, E. Schuuring, and P. M. Kluin. "Clinical Relevance of BCL2, BCL6, and MYC Rearrangements in Diffuse Large B-Cell Lymphoma." Blood 92, no. 9 (November 1, 1998): 3152–62. http://dx.doi.org/10.1182/blood.v92.9.3152.421a07_3152_3162.
Full textAbstract:
Diffuse large B-cell lymphoma (DLCL) is characterized by a marked degree of morphologic and clinical heterogeneity. We studied 156 patients with de novo DLCL for rearrangements of the BCL2, BCL6, and MYC oncogenes by Southern blot analysis and BCL2 protein expression. We related these data to the primary site of presentation, disease stage, and other clinical risk factors. Structural alterations of BCL2, BCL6, and MYC were detected in 25 of 156, 36 of 116, and 10 of 151 patients, respectively. Three cases showed a combination of BCL2 and BCL6 rearrangements, and two cases had a combination of BCL6 and MYC rearrangements. BCL2 rearrangement was found more often in extensive (39%) and primary nodal (17%) lymphomas than in extranodal cases (4%) (P = .003). BCL2 rearrangement was present in none of 40 patients with stage I disease, but in 22% of patients with stage II to IV (P = .006). The presence of BCL2 rearrangements did not significantly affect overall survival (OS) or disease-free survival (DFS). In contrast, high BCL2 protein expression adversely affected both OS (P = .008) and DFS (P = .01). BCL2 protein expression was poorly correlated with BCL2 rearrangement: only 52% of BCL2-rearranged lymphomas and 37% of BCL2-unrearranged cases had high BCL2 protein expression. Rearrangement of BCL6 was found more often in patients with extranodal (36%) and extensive (39%) presentation versus primary nodal disease (28%). No significant correlation was found with disease stage, lymphadenopathy, or bone marrow involvement. DFS and OS were not influenced by BCL6 rearrangements. MYC rearrangements were found in 16% of primary extranodal lymphomas, versus 2% of primary nodal cases (P = .02). In particular, gastrointestinal (GI) lymphomas (5 of 18 cases, 28%) were affected by MYC rearrangements. The distinct biologic behavior of these extranodal lymphomas was reflected by a high complete remission (CR) rate: 7 of 10 patients with MYC rearrangement attained complete remission and 6 responders remained alive for more than 4 years, resulting in a trend for better DFS (P = .07). These data show the complex nature of molecular events in DLCL, which is a reflection of the morphologic and clinical heterogeneity of these lymphomas. However, thus far, these genetic rearrangements fail as prognostic markers. © 1998 by The American Society of Hematology.
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Pittaluga, S., M. Raffeld, EH Lipford, and J. Cossman. "3A1 (CD7) expression precedes T beta gene rearrangements in precursor T (lymphoblastic) neoplasms." Blood 68, no. 1 (July 1, 1986): 134–39. http://dx.doi.org/10.1182/blood.v68.1.134.134.
Full textAbstract:
Abstract The phenotypes of early stages of T cell maturation are reflected by precursor T (lymphoblastic) neoplasms. In the present study, a series of such neoplasms was analyzed to reveal the developmental association of the expression of stage-related cell surface markers and T cell receptor gene rearrangement. Rearrangements of the T cell receptor beta- chain (T beta) gene were found in most, but not all, cases (88%) of T cell lymphoblastic neoplasms. T beta gene rearrangement preceded surface expression of the T cell receptor-linked molecular complex T3. Of all monoclonal anti-T cell antibodies tested, only antibody 3A1 was capable of reacting with neoplastic cells from all cases irrespective of the occurrence of T cell receptor gene rearrangements. In contrast, markers T1 and T11, normally expressed by mature T cells, were absent from the neoplastic cells in many cases (73% and 60% positive cases, respectively). Thus, antibody 3A1 is a valuable probe for the identification of T lymphoblastic neoplasms since its target antigen is consistently expressed and does not require prior T beta gene rearrangement. Furthermore, expression of 3A1 prior to T beta gene rearrangement suggests that it may be a cell surface protein that participates in the triggering of T cell receptor gene rearrangement and expression. It is concluded that precursor T cell neoplasms display an early T cell development hierarchy that, in sequence, consists of 3A1 expression, T beta gene rearrangements, and surface T3 expression.
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Pittaluga, S., M. Raffeld, EH Lipford, and J. Cossman. "3A1 (CD7) expression precedes T beta gene rearrangements in precursor T (lymphoblastic) neoplasms." Blood 68, no. 1 (July 1, 1986): 134–39. http://dx.doi.org/10.1182/blood.v68.1.134.bloodjournal681134.
Full textAbstract:
The phenotypes of early stages of T cell maturation are reflected by precursor T (lymphoblastic) neoplasms. In the present study, a series of such neoplasms was analyzed to reveal the developmental association of the expression of stage-related cell surface markers and T cell receptor gene rearrangement. Rearrangements of the T cell receptor beta- chain (T beta) gene were found in most, but not all, cases (88%) of T cell lymphoblastic neoplasms. T beta gene rearrangement preceded surface expression of the T cell receptor-linked molecular complex T3. Of all monoclonal anti-T cell antibodies tested, only antibody 3A1 was capable of reacting with neoplastic cells from all cases irrespective of the occurrence of T cell receptor gene rearrangements. In contrast, markers T1 and T11, normally expressed by mature T cells, were absent from the neoplastic cells in many cases (73% and 60% positive cases, respectively). Thus, antibody 3A1 is a valuable probe for the identification of T lymphoblastic neoplasms since its target antigen is consistently expressed and does not require prior T beta gene rearrangement. Furthermore, expression of 3A1 prior to T beta gene rearrangement suggests that it may be a cell surface protein that participates in the triggering of T cell receptor gene rearrangement and expression. It is concluded that precursor T cell neoplasms display an early T cell development hierarchy that, in sequence, consists of 3A1 expression, T beta gene rearrangements, and surface T3 expression.
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Tycko, B., H. Coyle, and J. Sklar. "Chimeric gamma-delta signal joints. Implications for the mechanism and regulation of T cell receptor gene rearrangement." Journal of Immunology 147, no. 2 (July 15, 1991): 705–13. http://dx.doi.org/10.4049/jimmunol.147.2.705.
Full textAbstract:
Abstract Rearrangement of Ag receptor genes requires recognition by the lymphocyte recombinase of heptamer-nonamer signal sequences followed by two endonucleolytic cleavages and two DNA ligations to form the coding and signal joints. The phenomenon of trans-rearrangement, in which Ag receptor gene segments located on different chromosomes recombine to yield chimeric products, provides an in vivo system in which to investigate the ability of the recombinase to carry out each of these functions in trans. Trans-rearrangements between TCRG and TCRD loci, similar in structure and frequency to those observed previously in human lymphoid tissues, were demonstrated in normal mouse thymus by PCR with crossed V gamma/J delta and V delta/J gamma primer pairs. A simple mechanistic model for trans-rearrangement was then tested. This model posits an ability of the recombinase to catalyze the formation of both coding and signal joints in trans and therefore predicts that trans-rearrangements will generate chimeric signal joints. In adult thymus, chimeric D delta 2-J gamma 1 and D delta 2-J gamma 2 signal joints, containing fused heptamer-nonamer sequences, could be detected by PCR and were each present at frequencies sufficient to account for a large proportion of the corresponding TCRG/TCRD trans-rearrangements. In agreement with the predictions of the model, chimeric signal joints were found as both linear chromosomal and circular episomal DNA. The results provide a framework for understanding the formation of chromosomal translocations in normal and neoplastic lymphoid cells and support the possibility of a looping mechanism for standard gene rearrangement. To test the form of regulation of TCRG rearrangement, the frequencies of specific signal joints from standard and trans-rearrangements were compared. Although J gamma 1 and J gamma 2 segments participated with equal frequency in trans-rearrangement with D delta 2, only the J gamma 1 segment participated in standard rearrangement with V gamma 5. The results suggest that V-J recombination in the TCRG locus is regulated directly at the DNA level by cis-acting constraints which do not affect the accessibility of individual TCRG gene segments to recombination in trans.
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Ramsden, D. A., C. J. Paige, and G. E. Wu. "Kappa light chain rearrangement in mouse fetal liver." Journal of Immunology 153, no. 3 (August 1, 1994): 1150–60. http://dx.doi.org/10.4049/jimmunol.153.3.1150.
Full textAbstract:
Abstract Ig variable domains are generated by the recombination of V, D, and J segments (V(D)J rearrangement). V(D)J rearrangement is capable of generating a vast repertoire of different variable domains. In this report, we quantify and characterize the repertoire of kappa rearrangements in fetal liver ontogeny. VJ kappa rearrangements are first observable at approximately day 14 of gestation. Characterization of these rearrangements indicates that only 33% are in a productive reading frame, which supports the argument that they have been generated recently and have not as yet undergone significant Ag-driven selection. Further analysis of rearrangements from a pool of 133 cloned VJ kappa junctions (from both day 14 and day 16 of gestation) indicates that the repertoire is fairly diverse with respect to the V kappa gene families used, as well as the number of members from each gene family. The frequency of V kappa 4 family use in rearrangements to J kappa 5, however, was approximately twice that of the frequency of V kappa 4 family use in rearrangement to other J kappa s. The fine structure of fetal VJ kappa junctions was also diverse, which indicates that precise deletion of sequence identities shared between rearranging V kappa J kappa pairs does not significantly reduce junctional diversity, as has been observed in DJH rearrangements. Lastly, a number of junctions contained P nucleotides, in contrast to the repertoire of expressed VJ kappa junctions.
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Kerwin, Sean M., Ashley L. Jewett, Joshua A. Bondoc, Bradford L. Gilbreath, and Brandon J. Reinus. "Spirocyclic Products via Carbene Intermediates from Thermolysis of 1,2-Dialkynylpyrrole and 1,2-Diethynylimidazole." Synlett 33, no. 07 (March 17, 2022): 674–78. http://dx.doi.org/10.1055/s-0041-1737937.
Full textAbstract:
AbstractThe thermal rearrangements of 1,2-dialkynylimidazoles have been shown to lead to trapping products of cyclopenta[b]pyrazine carbene intermediates. Here we show that a similar rearrangement also occurs in the case of 1,2-diethynyl-1H-pyrrole, and that trapping the intermediate cyclopenta[b]pyridine carbene with solvent THF affords an ylide that undergoes a Stevens rearrangement to a spirocyclic product. An analogous rearrangement and trapping is observed for thermolysis of 1,2-dialkynylimidazoles in THF or 1,4-dioxane.