Academic literature on the topic 'Intraclonal'
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Journal articles on the topic "Intraclonal"
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Gurrieri, Carmela, Peter McGuire, Hong Zan, Xiao-Jie Yan, Andrea Cerutti, Emilia Albesiano, Steven L. Allen, et al. "Chronic Lymphocytic Leukemia B Cells Can Undergo Somatic Hypermutation and Intraclonal Immunoglobulin VHDJH Gene Diversification." Journal of Experimental Medicine 196, no. 5 (September 2, 2002): 629–39. http://dx.doi.org/10.1084/jem.20011693.
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Chronic lymphocytic leukemia (CLL) arises from the clonal expansion of a CD5+ B lymphocyte that is thought not to undergo intraclonal diversification. Using VHDJH cDNA single strand conformation polymorphism analyses, we detected intraclonal mobility variants in 11 of 18 CLL cases. cDNA sequence analyses indicated that these variants represented unique point-mutations (1–35/patient). In nine cases, these mutations were unique to individual submembers of the CLL clone, although in two cases they occurred in a large percentage of the clonal submembers and genealogical trees could be identified. The diversification process responsible for these changes led to single nucleotide changes that favored transitions over transversions, but did not target A nucleotides and did not have the replacement/silent nucleotide change characteristics of antigen-selected B cells. Intraclonal diversification did not correlate with the original mutational load of an individual CLL case in that diversification was as frequent in CLL cells with little or no somatic mutations as in those with considerable mutations. Finally, CLL B cells that did not exhibit intraclonal diversification in vivo could be induced to mutate their VHDJH genes in vitro after stimulation. These data indicate that a somatic mutation mechanism remains functional in CLL cells and could play a role in the evolution of the clone.
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Volkheimer, Alicia D., J. Brice Weinberg, Bethany E. Beasley, John F. Whitesides, Jon P. Gockerman, Joseph O. Moore, Garnett Kelsoe, Barbara K. Goodman, and Marc C. Levesque. "Progressive immunoglobulin gene mutations in chronic lymphocytic leukemia: evidence for antigen-driven intraclonal diversification." Blood 109, no. 4 (November 2, 2006): 1559–67. http://dx.doi.org/10.1182/blood-2006-05-020644.
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Abstract Somatic mutations of immunoglobulin genes characterize mature memory B cells, and intraclonal B-cell diversification is typically associated with expansion of B-cell clones with greater affinity for antigen (antigen drive). Evidence for a role of antigen in progression of intraclonal chronic lymphocytic leukemia (CLL) cell diversification in patients with mutated immunoglobulin genes has not been previously presented. We performed a single-cell analysis of immunoglobulin heavy and light chains in 6 patients with somatically mutated CLL-cell immunoglobulin genes and identified 2 patients with multiple related (oligoclonal) subgroups of CLL cells. We constructed genealogic trees of these oligoclonal CLL-cell subgroups and assessed the effects of immunoglobulin somatic mutations on the ratios of replacement and silent amino acid changes in the framework and antigen-binding regions (CDRs) of the immunoglobulin heavy and light chains from each oligoclonal CLL-cell population. In one subject, the amino acid changes were consistent with an antigen-driven progression of clonally related CLL-cell populations. In the other subject, intraclonal diversification was associated with immunoglobulin amino acid changes that would have likely lessened antigen affinity. Taken together, these studies support the hypothesis that in some CLL cases intraclonal diversification is dependent on antigen interactions with immunoglobulin receptors.
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Rawstron, Andy C., James A. L. Fenton, Marieth Plummer, Harry O. King, Fiona L. Bennett, Andrew S. Jack, and Peter Hillmen. "Monoclonal B-Cell Lymphocytosis (MBL) and CLL Show Intraclonal Variation: Cases Classified as “Unmutated” Have the Greatest Clonal Diversity." Blood 108, no. 11 (November 16, 2006): 30. http://dx.doi.org/10.1182/blood.v108.11.30.30.
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Abstract A monoclonal B-cell lymphocytosis (MBL) is detectable in approximately 3% of the general adult population. In most cases the abnormal cells have a phenotype and genotype that is indistinguishable from indolent CLL. Individuals presenting with an MBL count over 500 cells per microlitre progress to CLL requiring treatment at a rate of approximately 1% per year. The relationship between MBL and CLL therefore appears to be similar to that of MGUS and myeloma. Intraclonal variation (ICV) in the immunoglobulin heavy chain gene (IgVH) gene occurs in approximately half of MGUS patients but is not present in myeloma. The majority MGUS patients that progress to myeloma lack intraclonal variation at the MGUS stage suggesting that clonal selection is a critical pathway for disease progression in myeloma. The aim of this study was to compare the rate of intraclonal variation in MBL and CLL and determine whether low rates of ICV are associated with progressive disease. DNA was extracted from ammonium-chloride lysed blood samples from individuals with CLL-phenotype MBL (n=20) and CLL with progressive disease (n=10). IgVH and BCL6 PCR products were directly sequenced and also cloned and at least 10 clones sequenced. Intraclonal variation was defined as the number of unique sequences as a percentage of total clones sequenced. Unmutated CLL was defined as having <2% difference in the predominant IgVH clone sequence from germline. The median IgVH mutation rate in the MBL group was 7.4% (range 1.3–13.7%) and in the progressive CLL group 0.6% (range 0–11.3%). Intraclonal variation was observed in both groups of patients: the median number of unique clones was 2/10 (range 0–7/10) in MBL patients and 3/10 (range 0–5/10) in CLL patients. Intraclonal variation was generally restricted to 1 or 2 point mutations in each sequence and for the VH gene the replacement/silent (R/S) ratio of mutations was 1.7 in the framework regions and 3.3 in the complementarity-determining regions. Independent of disease category, unmutated CLL/MBL had a higher degree of intraclonal variation than mutated CLL with a median ICV for unmutated cases of 31% and for mutated cases of 20%. The proportion of patients showing complete clonal homogeneity was lower for unmutated CLL/MBL (14%) than mutated CLL/MBL (27%). The BCL6 gene, which is also mutated during the canonical somatic hypermutation process, showed similar results with a greater degree of intraclonal variation in unmutated CLL/MBL. The results demonstrate that intraclonal variation is a frequent occurrence in both MBL and CLL particularly when non-immunoglobulin genes are also considered. Clonal heterogeneity is either independent of, or inversely related to, the immunoglobulin mutation status demonstrating that both mutated and unmutated CLL have undergone (or are continuing to undergo) somatic hypermutation. The mechanisms of disease progression in MBL/CLL are clearly biologically distinct from MGUS/Myeloma and this data provides strong evidence for an antigen-driven selection process in CLL. Disease progression in CLL may therefore be the result of continued activity of the somatic hypermutation machinery, demonstrated by AID expression in some patients. Coupled with a selective pressure to maintain the immunoglobulin gene this process may result in the selection of CLL clones with transforming mutations in non-immunoglobulin genes.
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Rajamanickam, C., and K. Rajmohan. "Intraclonal Variation in Musa (AAB) Palayankodan." International Journal of Current Microbiology and Applied Sciences 9, no. 6 (June 10, 2020): 269–75. http://dx.doi.org/10.20546/ijcmas.2020.906.034.
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Zojer, Niklas, Heinz Ludwig, Michael Fiegl, Freda K. Stevenson, and Surinder S. Sahota. "Patterns of somatic mutations in VH genes reveal pathways of clonal transformation from MGUS to multiple myeloma." Blood 101, no. 10 (May 15, 2003): 4137–39. http://dx.doi.org/10.1182/blood-2002-09-2825.
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AbstractMonoclonal gammopathy of undetermined significance (MGUS) can transform to multiple myeloma (MM). In myeloma, mutated VHgenes with sequence homogeneity reveal a postfollicular origin. Previously, some MGUS cases showed mutated VH genes with intraclonal variation, indicating an earlier stage of arrest. We investigated progression from 2 of 2 MGUS to MM, in which VH genes confirmed clonal evolution. In one MGUS case, intraclonal heterogeneity was evident, and transformation to myeloma occurred rapidly with apparent homogeneity in the emergent clone. However, residual MGUS-derived sequences were detectable at this time. Heterogeneity in MGUS does not associate with benign disease, but it indicates an origin from a tumorigenic cell, most likely surface immunoglobulin+, undergoing somatic mutation. The remaining case displayed intraclonal homogeneity at the MGUS stage, conceivably resulting from a self-cloning outgrowth from MGUS with heterogeneity. Transformation can occur at either MGUS stage, but it involves a single cell in which somatic mutation is then silent.
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Bartholdy, Boris A., Xiahoua Wang, Xiao-Jie Yan, Marién Pascual, Manxia Fan, Jacqueline Barrientos, Steven L. Allen, et al. "CLL intraclonal fractions exhibit established and recently acquired patterns of DNA methylation." Blood Advances 4, no. 5 (March 9, 2020): 893–905. http://dx.doi.org/10.1182/bloodadvances.2019000817.
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Abstract Intraclonal subpopulations of circulating chronic lymphocytic leukemia (CLL) cells with different proliferative histories and reciprocal surface expression of CXCR4 and CD5 have been observed in the peripheral blood of CLL patients and named proliferative (PF), intermediate (IF), and resting (RF) cellular fractions. Here, we found that these intraclonal circulating fractions share persistent DNA methylation signatures largely associated with the mutation status of the immunoglobulin heavy chain locus (IGHV) and their origins from distinct stages of differentiation of antigen-experienced B cells. Increased leukemic birth rate, however, showed a very limited impact on DNA methylation of circulating CLL fractions independent of IGHV mutation status. Additionally, DNA methylation heterogeneity increased as leukemic cells advanced from PF to RF in the peripheral blood. This frequently co-occurred with heterochromatin hypomethylation and hypermethylation of Polycomb-repressed regions in the PF, suggesting accumulation of longevity-associated epigenetic features in recently born cells. On the other hand, transcriptional differences between paired intraclonal fractions confirmed their proliferative experience and further supported a linear advancement from PF to RF in the peripheral blood. Several of these differentially expressed genes showed unique associations with clinical outcome not evident in the bulk clone, supporting the pathological and therapeutic relevance of studying intraclonal CLL fractions. We conclude that independent methylation and transcriptional landscapes reflect both preexisting cell-of-origin fingerprints and more recently acquired hallmarks associated with the life cycle of circulating CLL cells.
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Hale, Anna L., J. Creighton Miller, K. Renganayaki, Alan K. Fritz, J. J. Coombs, L. M. Frank, and D. S. Douches. "Suitability of AFLP and Microsatellite Marker Analysis for Discriminating Intraclonal Variants of the Potato Cultivar Russet Norkotah." Journal of the American Society for Horticultural Science 130, no. 4 (July 2005): 624–30. http://dx.doi.org/10.21273/jashs.130.4.624.
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The objective of this study was to differentiate six intraclonal variants of the potato (Solanum tuberosum L.) cultivar Russet Norkotah. One-hundred-twelve AFLP primer combinations producing 3755 bands and 79 microsatellite primers producing over 400 bands failed to identify any reproducible polymorphisms among the intraclonal variants and `Russet Norkotah'. The inability to detect differences between clones underscores the degree of genetic similarity between them, despite differences in phenotypic expression. This inability could be due to the tetraploid nature of the clones and/or to epigenetic differences not detected by the utilized procedures.
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Beke, Allan, Lucie Laplane, Julie Riviere, Qin Yang, Miguel Torres-Martin, Thibault Dayris, Philippe Rameau, et al. "Multilayer intraclonal heterogeneity in chronic myelomonocytic leukemia." Haematologica 105, no. 1 (May 2, 2019): 112–23. http://dx.doi.org/10.3324/haematol.2018.208488.
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Aarts, Wilhelmina M., Richard J. Bende, Eric J. Steenbergen, Philip M. Kluin, Engelbert C. M. Ooms, Steven T. Pals, and Carel J. M. van Noesel. "Variable heavy chain gene analysis of follicular lymphomas: correlation between heavy chain isotype expression and somatic mutation load." Blood 95, no. 9 (May 1, 2000): 2922–29. http://dx.doi.org/10.1182/blood.v95.9.2922.009k38_2922_2929.
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The expansion of follicular lymphomas (FLs) resembles, both morphologically and functionally, normal germinal center B-cell growth. The tumor cells proliferate in networks of follicular dendritic cells and are believed to be capable of somatic hypermutation and isotype switching. To investigate the relation between somatic mutation and heavy chain isotype expression, we analyzed the variable heavy (VH) chain genes of 30 FL samples of different isotypes. The VH genes of the FLs were heavily mutated (29.3 mutations on average). In addition, isotype-switched lymphomas contained more somatic mutations than immunoglobulin M–positive lymphomas (33.8 mutations per VH gene versus 23.0, respectively). In all but one of the FLs, the ratios of replacement versus silent mutations in the framework regions were low, independent of the absolute number of somatic mutations and the level of intraclonal variation. Analysis of relapse samples of 4 FLs showed no obvious increase in somatic mutation load in most FLs and a decrease in intraclonal variation in time. In 3 of 4 cases, we obtained evidence for selection of certain subclones, rather than clonal evolution. Our findings question if intraclonal variation is always a reflection of ongoing somatic hypermutation. This may have implications for the concept of antigen-driven lymphomagenesis.
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Fagerström, T., and A. G. B. Poore. "Intraclonal Variation in Macroalgae: Causes and Evolutionary Consequences." Selection 1, no. 1-3 (January 2001): 123–34. http://dx.doi.org/10.1556/select.1.2000.1-3.12.
Full textDissertations / Theses on the topic "Intraclonal"
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Marie, Joan. "Intraclonal Morphological Plasticity within the Myzus persicae (Sulzer) Complex Related to Host Plant and Temperature." Thesis, Virginia Tech, 2004. http://hdl.handle.net/10919/33305.
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Blackman (1987) used life cycle and morphology to separate Myzus nicotianae Blackman, a tobacco-feeding species of aphid, from Myzus persicae (Sulzer). In the present study, the first objective was to investigate the influence of temperature and host plant on the morphology of M. nicotianae and M. persicae. The second objective was to assess Blackman¡¦s 1987 key to Myzus for separating tobacco and non-tobacco originating morphs under different environmental conditions. Four host plants were used: tobacco, turnip, pepper, and okra, and three temperatures, 15â aC, 20â aC, and 25â aC. The intraclonal plasticity of two tobacco collected morphs and one turnip collected morph was investigated in relation to these combinations of host and temperature in a 4 x 3 x 3 factorial experimental design. Fifth generation mature apterous aphids were mounted on slides and 10 different morphological structures utilized in morphometric analysis were measured.
Data support a morphologically distinct, host-adapted tobacco race but not a separate tobacco-feeding species of M. persicae. The key developed by Blackman (1987) did not discriminate between the tobacco and non-tobacco originating clones but the canonical variates generated from the analysis successfully separated the tobacco and non-tobacco groups. Other studies have used many different clones to investigate the possible distinctions between M. persicae and M. nicotianae; the objective here was to see how much morphological perturbation may be induced within a clone by rearing at different temperatures and on different host plants.
Temperature and host plant had substantial influences on the morphology of these aphids. The physiological interactions of temperature-host plant-aphid morphology are very complex yet controlling only for temperature and host plant was sufficient to group specimens according to these independent variables with remarkable accuracy using the linear discriminant functions generated with these data. Percent of aphids in which rearing temperature was correctly identified using linear discriminant functions generated for temperature classes was 87%, 63%, and 64% for 15â aC, 20â aC, and 25â aC, respectively. Random designations would be 33%. Correct identification of host plant was 65%, 45%, 47%, and 48% successful for tobacco, turnip, pepper, and okra, respectively. Random designations for host plant would be 25%.
Canonical variates produced clusters by host, temperature, morph, and combinations of these independent variables with varying degrees of discreteness. CV1 by CV2 for host plants gave a very distinct cluster for tobacco and also separate groupings for aphids reared on turnip and pepper. Aphids from the host plant okra were scattered quite widely across the CV1 by CV2 graph. CV1 by CV2 for temperature conditions showed a tight cluster for aphids from 15â aC and still distinct though less closely grouped clusters for both 20â aC and 25â aC rearing temperatures. CV1 by CV2 for the three morphs gave substantial overlap for the two tobacco originating morphs and a more separate cluster for the morph originally collected from turnip.Master of Science
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Martin, Patricia. "La génération d'un polymorphisme génétique intraclonal est modulée pendant la différenciation chez Streptomyces ambofaciens ATCC23877." Nancy 1, 2000. http://www.theses.fr/2000NAN10110.
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Chez S. Ambofaciens, la pigmentation des colonies est un caractère instable. Ce phénomène se traduit par la production de 4 types de colonie dans la descendance d’une colonie pigmentée dite sauvage (WT) : des colonies pigmentées (Pig+), des colonies dépigmentées (Pig-col), des colonies pigmentées à secteur dépigmenté (Pig+sec) ou à papilles dépigmentées (Pig+pap). Des réarrangements (délétion et/ou amplification) ont été observés dans les mutants Pig-col. Un polymorphisme génétique important a été révélé au sein de 12 sous-clones WT, tant au niveau phénotypique (variation des fréquences de Pig-col, de Pig +sec et des distributions du nombre de papilles par colonie) que génomique (variation des fréquences de délétion parmi les Pig-col et les Pig-sec, mutants dérivés de secteurs dépigmentés). […] La signification biologique du polymorphisme intraclonal et de la formation à haute fréquence de souches mutatrices sera discutée. L’idée selon laquelle ce phénomène, correspondant à la non reproduction à l’identique du génome de la bactérie, participerait activement à l’évolution de S. Ambofaciens sera développée. Les fonctions impliquées dans l’état mutateur et dans la variation quantitative de cet état seront également envisagées. Enfin, différentes hypothèses seront avancées pour expliquer la nature des mutants Pig-pap, qui traduisent un nouvel aspect de l’instabilité génétique.
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Brioli, Annamaria <1982>. "The impact of intraclonal heterogeneity on the outcomes of Multiple Myeloma patients treated with new drugs." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2015. http://amsdottorato.unibo.it/6779/1/Brioli_Annamaria_tesi.pdf.
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Understanding the biology of Multiple Myeloma (MM) is of primary importance in the struggle to achieve a cure for this yet incurable neoplasm. A better knowledge of the mechanism underlying the development of MM can guide us in the development of new treatment strategies. Studies both on solid and haematological tumours have shown that cancer comprises a collection of related but subtly different clones, a feature that has been termed “intra-clonal heterogeneity”. This intra-clonal heterogeneity is likely, from a “Darwinian” natural selection perspective, to be the essential substrate for cancer evolution, disease progression and relapse. In this context the critical mechanism for tumour progression is competition between individual clones (and cancer stem cells) for the same microenvironmental “niche”, combined with the process of adaptation and natural selection. The Darwinian behavioural characteristics of cancer stem cells are applicable to MM. The knowledge that intra-clonal heterogeneity is an important feature of tumours’ biology has changed our way to addressing cancer, now considered as a composite mixture of clones and not as a linear evolving disease. In this variable therapeutic landscape it is important for clinicians and researchers to consider the impact that evolutionary biology and intra-clonal heterogeneity have on the treatment of myeloma and the emergence of treatment resistance. It is clear that if we want to effectively cure myeloma it is of primarily importance to understand disease biology and evolution. Only by doing so will we be able to effectively use all of the new tools we have at our disposal to cure myeloma and to use treatment in the most effective way possible. The aim of the present research project was to investigate at different levels the presence of intra-clonal heterogeneity in MM patients, and to evaluate the impact of treatment on clonal evolution and on patients’ outcomes.
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Brioli, Annamaria <1982>. "The impact of intraclonal heterogeneity on the outcomes of Multiple Myeloma patients treated with new drugs." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2015. http://amsdottorato.unibo.it/6779/.
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Understanding the biology of Multiple Myeloma (MM) is of primary importance in the struggle to achieve a cure for this yet incurable neoplasm. A better knowledge of the mechanism underlying the development of MM can guide us in the development of new treatment strategies. Studies both on solid and haematological tumours have shown that cancer comprises a collection of related but subtly different clones, a feature that has been termed “intra-clonal heterogeneity”. This intra-clonal heterogeneity is likely, from a “Darwinian” natural selection perspective, to be the essential substrate for cancer evolution, disease progression and relapse. In this context the critical mechanism for tumour progression is competition between individual clones (and cancer stem cells) for the same microenvironmental “niche”, combined with the process of adaptation and natural selection. The Darwinian behavioural characteristics of cancer stem cells are applicable to MM. The knowledge that intra-clonal heterogeneity is an important feature of tumours’ biology has changed our way to addressing cancer, now considered as a composite mixture of clones and not as a linear evolving disease. In this variable therapeutic landscape it is important for clinicians and researchers to consider the impact that evolutionary biology and intra-clonal heterogeneity have on the treatment of myeloma and the emergence of treatment resistance. It is clear that if we want to effectively cure myeloma it is of primarily importance to understand disease biology and evolution. Only by doing so will we be able to effectively use all of the new tools we have at our disposal to cure myeloma and to use treatment in the most effective way possible. The aim of the present research project was to investigate at different levels the presence of intra-clonal heterogeneity in MM patients, and to evaluate the impact of treatment on clonal evolution and on patients’ outcomes.
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Sutton, Lesley Ann. "Molecular and Genetic Evidence for Antigen Selection in the Pathogenesis of Chronic Lymphocytic Leukemia." Doctoral thesis, Uppsala universitet, Hematologi och immunologi, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-181602.
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Antigens play a critical role in the development of chronic lymphocytic leukemia (CLL) by binding to and stimulating leukemic precursor cells at some point during CLL ontogeny. Nevertheless, much remains unknown and further studies are necessary before an accurate model of antigen-drive can be ascertained. In this context, intraclonal diversification (ID) analysis of immunoglobulin (IG) genes could shed light on whether antigen involvement is restricted to the malignant transformation phase or if the triggering antigen(s) continuously stimulates the CLL clone. Hence, in Paper I we conducted a large-scale analysis of 71 CLL cases and revealed that 28/71 cases carried intraclonally diversified IGHV-IGHD-IGHJ genes. Although most cases showed no or low levels of ID, intense ID was evident within all subset #4 (IGHV4-34/IGKV2-30) cases. Subsequent analysis, in Paper II, of the clonotypic light chains revealed that the outstanding exception again related to subset #4. In such cases, the expressed IGKV2-30 gene was affected by targeted ID, analogous to their partner IGHV4-34 gene. Whilst these results convincingly argued for the role of antigen(s) in the development and evolution of CLL subset #4, this analysis was limited to depicting what was occurring at a single time-point and could not provide insight into the temporal dynamics of the CLL clones. Thus, in Paper III we conducted a longitudinal study of 8 subset #4 cases which enabled us to establish a hierarchical pattern of subclonal evolution. The observed ‘stepwise’ accumulation of mutations strongly supports a role for antigen selection in the pathogenesis of CLL subset #4. In Paper IV we reported a subset of IgG-switched CLL patients with coexisting trisomies of 12 and 19, and propose that the emergence of trisomy 18 in such cases represents a clonal evolution event suggestive of selection due to a clonal advantage. Paper V focused on the IGHV3-21 gene, an adverse prognostic factor in CLL. Since ~60% of IGHV3-21-expressing cases carry stereotyped B cell receptors, recognition of a common antigenic epitope, perhaps of pathogenic significance, is envisaged. Therefore, we investigated IGHV3-21 gene frequency within a Swedish population-based cohort and assessed the impact of stereotypy on clinical outcome. Taken collectively, this thesis provides molecular and genetic evidence for the role of antigen in CLL pathogenesis by convincingly demonstrating that clonal evolution, at least for certain subsets of CLL, is functionally driven rather than a consequence of clonal expansion promoted by nonspecific stimuli.
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Vorwerk, Sonja. "Molecular evidence of intraclonal variation and implications for adaptational traits of grape phylloxera populations (Daktulosphaira vitifoliae, Fitch)." [S.l. : s.n.], 2007. http://nbn-resolving.de/urn:nbn:de:bsz:100-opus-2086.
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Jacobs, Claudia. "Untersuchung entfernt lokalisierter Gewebeproben kutaner B-Zell-Lymphome auf intraklonale Diversität mit der Einzel-Zell-PCR-Technik." Doctoral thesis, Humboldt-Universität zu Berlin, Medizinische Fakultät - Universitätsklinikum Charité, 2000. http://dx.doi.org/10.18452/14571.
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Zusammenfassung Die molekularbiologischen Untersuchungen der variablen Genabschnitte der Immunglobulingene von Lymphomzellen zweier Patienten mit kutanen B-Zell-Lymphomen wurden in der vorliegenden Arbeit mittels Einzel-Zell-PCR-Technik durchgeführt. Die erfolgte Analyse galt bevorzugt dem Aspekt der intraklonalen Diversität. Die Sequenzanalysen der Ig-Gene für die leichte Kette aus den insgesamt 100 untersuchten Tumorzellen des Patienten WS ergaben, daß zwischen den Zellen aus drei voneinander entfernt lokalisierten Gewebeproben intraklonale Diversität vorlag. Aufgrund der Mutationsanalysen und der Zuordnung der Subklone zu den Entnahmeorten ist eine evtl. antigengetriebene Entwicklung des Tumorklons zu vermuten. Bei Patient LB konnte trotz des großen Aufwandes, der Untersuchung von insgesamt 126 Zellen aus acht räumlich getrennten Biopsien, keine intraklonale Diversität für die schwere Kette der Immunglobulingene aufgezeigt werden. Die Sequenzunterschiede der leichten Kette beruhen auf einer einzigen stummen Mutation im Bereich der CDR 1, die keinen funktionellen Einfluß auf die Aminosäuresequenz hat und deshalb geringe prognostische Bedeutung besitzt. In beiden Fällen lagen hypermutierte Immunglobulingene vor. Die Tumorzellen des Patienten WS sind aus molekularbiologischer Sicht Keimzentrumszellen, die des Patienten LB eher Nachkeimzentrumszellen zuzuordnen. Die gewonnenen Erkenntnisse zeigen, daß bei der Untersuchung und Erforschung der Pathogenese von kutanen B-Zell-Lymphomen eine gewonnene Gewebeprobe nicht repräsentativ für den gesamten Tumor sein muß. Veröffentliche Ergebnisse, bei denen Monoklonalität anhand einer Biopsie postuliert wurde, müssen daher initial überdacht werden (74;76;77;84). Es ist folglich in Betracht zu ziehen, daß bei einer exakten molekularbiologischen Zuordnung der Tumorzellen zu ihrem Entwicklungsstadium und ihrer Herkunft räumliche als auch zeitliche Faktoren zu beachten sind. Eine chronologische Untersuchung könnte aufzeigen, ob andauernde Mutationen in den Tumorzellen stattfinden. Die Mikromanipulation und die Einzel-Zell-PCR-Technik sind elegante Methoden, um intraklonale Sequenzunterschiede aufzuzeigen und einen Beitrag für die molekularbiologische Erforschung der Pathogenese von kutanen B-Zell-Lymphomen zu leisten. Eine Kontrolle von malignoproliferativen Krankheiten, ob es unter den heutigen Therapiemöglichkeiten gelingt, den malignen Tumorklon vollständig zu beseitigen oder Aussagen über Progredienz und Prognose zu treffen, wäre ein interessanter Einsatzbereich dieser Methode.abstract The molecularbiological investigation of the immunoglobulin variable region genes of two patients suffering on primary cutaneous B-cell-lymphoma was carried out using single-cell- PCR technic. The main focus lay on the aspect on the aspect of detecting intraclonal diversity. The sequence nucleotid-analysises of the immunoglubulin light chain genes obtained from a total of 100 investigated tumor B-cells in patient WS revealed intraclonal diversity among cells isolated from three spatially separated tissue samples. Considering the mutational pattern and the subclones in dependence on the tumorcells, taken from different topographical tumorsides, an antigen-driven clonal expansion could be supposed. Despite extensive efforts and the analysis of altogether 126 tumor B-cells out of eight spatially different localised biopsies, no intraclonal diversity could be observed for the immunoglobulin heavy chain rearrangement of second patient LB. Sequence differences of the Ig light chain based on only a single silent mutation within the CDR1 region. This mutation has no functional affect of the amino acid sequence and therefore little prognostical significance. In both cases the immunoglobulin genes were somatically hypermutated in compromise to the germ-line gene. From the molecularbiological point of view, the tumor cells of patient WS descended from germinal center cells, whereas the tumor B-cells of patient LB rather can be characterized as post-germinal center cells. The results clearly demonstrate, that the investigation of a single tissue sample of primary cutaneous B-cell lymphoma using micromanipulation and single cell-PCR technic may not be representative for the whole tumor. Publications concluding monoclonality with no intraclonal diversity from the analysis of a single biopsie therefore have to be interpreted with caution (74;76;77;84). Accordingly, an appropiate molecularbiological characterization of tumor B-cells regarding their developmental stage and origin has to consider spatial and time dependant aspects. Only the investigation of sequential biopsies may reliably detect ongoing mutations in tumor B-cells. The combination of micromanipulation and single cell PCR represents an elegant method to observe intraclonal diversity. The technic will give contribution to molecularbiological investigation of the pathogenesis of primary cutaneous B-cell lymphomas. It could be of interest to apply this method to the evaluation of current therapies with respect to its capability to eradicating the malignant cell clone completely, and to draw conclusions on disease progression and prognosis.
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Koyo, Jean-Prosper. "Bouturage et variabilité morphogénétique de clones de Terminalia superba Engler et Diels ou Limba du Sud-Congo." Paris 11, 1985. http://www.theses.fr/1985PA112011.
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Les études d’amélioration génétique du Terminalia superba par voie asexuée ont été entreprises au CONGO, dans le cadre d’un projet de reboisement industriel de cette espèce. Une centaine de Limba d’élite sélectionnés dans les forêts du sud du Congo, ont été clonés et font l’objet depuis 1976 de plusieurs expérimentations et observations. Si actuellement, le bouturage est acquis et la croissance des clones encourageante, il n’en est pas de même de la réjuvénilisation qui ne semble pas encore satisfaisante, en particulier pour les caractères de branchaison. En conclusion, nous suggérons un schéma d’amélioration qui concilie la méthode asexuée et sexuée à partir des tests de provenances qui viennent d’être mis en place à NGOUA 2Asexual propagation and morphogenetic clonal variability of Terminalia superba Engler and Diels (Limba) in South Congo. Genetic improvement of Terminalia superba by asexual propagation has been studied in Congo as part of an industrial reforestation project. One hundred elite Limba, selected in South Congo forests, were cloned and since 1976 have been studied in several trials. A technique of establishing cuttings is now well understood and the growth of clones is encouraging, but rejuvenation remains unsatisfactory, particularly as it affects branching. This thesis concludes with a suggested breeding scheme involving both sexual and asexual propagation of material being tested in recently established provenance trials
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Pires, Ana Marta Costa. "Free light chain: a marker of disesase and intraclonal heterogeneity indicator in intact immunoglobulin multiple myeloma." Master's thesis, 2019. https://hdl.handle.net/10216/124600.
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Pires, Ana Marta Costa. "Free light chain: a marker of disesase and intraclonal heterogeneity indicator in intact immunoglobulin multiple myeloma." Dissertação, 2019. https://hdl.handle.net/10216/124600.
Full textBook chapters on the topic "Intraclonal"
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Rainey, Paul B., Ian P. Thompson, and E. Richard Moxon. "Intraclonal Polymorphism in Bacteria." In Advances in Microbial Ecology, 263–300. Boston, MA: Springer US, 1993. http://dx.doi.org/10.1007/978-1-4615-2858-6_6.
Full textConference papers on the topic "Intraclonal"
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Jakubikova, Jana, Danka Cholujova, Teru Hideshima, Jacob Laubach, Nikhil C. Munshi, Steven P. Treon, Paul G. Richardson, Efstathios Kastritis, David M. Dorfman, and Kenneth C. Anderson. "Abstract 2004: Phenotypic and molecular characterization of inter- and intraclonal heterogeneity in multiple myeloma and Waldenstrom macroglobulinemia." In Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA. American Association for Cancer Research, 2015. http://dx.doi.org/10.1158/1538-7445.am2015-2004.
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