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Gangat, Naseema, Jacob J. Strand, Terra L. Lasho, Christy M. Finke, Ryan A. Knudson, Animesh Pardanani, Chin-Yang Li, Rhett P. Ketterling, and Ayalew Tefferi. "Cytogenetic Studies at Diagnosis in Polycythemia Vera: Clinical and JAK2V617F Allele Burden Correlates." Blood 110, no. 11 (November 16, 2007): 2545. http://dx.doi.org/10.1182/blood.v110.11.2545.2545.
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Abstract Background: Previous cytogenetic studies in polycythemia vera (PV) have included a relatively small number of patients (“n” ranging 10–64). In the current study (n=137), we describe cytogenetic findings at presentation and examine their relationship to clinical and laboratory features, including bone marrow JAK2V617F allele burden. Methods: The study consisted of a consecutive group of patients with PV who fulfilled the World Health Organization (WHO) diagnostic criteria and in whom bone marrow biopsy and cytogenetic studies were performed at diagnosis. Results I: cytogenetic details At diagnosis: A total of 137 patients (median age, 64 years; 49% females) were studied at diagnosis and had adequate metaphases for interpretation. Cytogenetics were normal in 117 patients (85%) and displayed either a sole -Y abnormality in 5 patients (7% of the male patients), and other chromosomal abnormalities in 15 (11%). The latter included trisomy 8 in five patients, trisomy 9 in three patients, two patients each with del(13q), del(20q), and abnormalities of chromosome 1, and one patient each with del(3)(p13p21), dup(13)(q12q14), and del(11)(q21). At follow-up: Repeat cytogenetic studies while still in the chronic phase of the disease were performed in 19 patients at a median of 60 months (range, 8–198) from diagnosis. Of these, 4 had aquired new cytogenetic clones including 3 with normal cytogenetics at time of initial PV diagnosis. The new abnormalities included del(20q), del(5q), del(1p), chromosome 1 abnormality, and inv(3)(q21q26.2). At time of disease transformation: Leukemic transformation was documented in 3 patients of whom cytogenetic information at the time was available in 2 patients; both patients had normal results at time of initial PV diagnosis and complex cytogenetic abnormalities at time of leukemic transformation. In contrast, among 6 patients with available cytogenetic information at time of fibrotic transformation, the results were unchanged from those obtained at time of diagnosis in 5 patients. ii) Correlation between cytogenetics at diagnosis and JAK2V617F allele burden: Allele-specific, quantitative PCR analysis for JAK2V617F was performed in 71 patients using genomic DNA from archived bone marrow obtained at the time of the initial cytogenetic studies. JAK2V617F mutation was detected in 64 of the 71 (90%) patients; median mutant allele burden was 16% (range 3–80%) without significant difference among the different cytogenetic groups: normal vs. –Y vs. other cytogenetic abnormalities (p=0.72). iii) Clinical correlates and prognostic relevance of cytogenetic findings at diagnosis: Among several parameters studied for significant correlations with cytogenetic findings at diagnosis, an association was evident only for age (p=0.02); all –Y abnormalities (n=5) as well as 13 of the 15 (87%) other cytogenetic abnormalities occurred in patients ≥ 60 years of age. Stated another way, the incidence of abnormal cytogenetics (other than -Y) was 4% for patients younger than age 60 years and 15% otherwise. The presence of abnormal cytogenetics at diagnosis had no significant impact on either overall or leukemia-free survival. Conclusions: Abnormal cytogenetic findings at diagnosis are infrequent in PV, especially in patients below age 60 years. Furthermore, their clinical relevance is limited and there is not significant correlation with bone marrow JAK2V617F allele burden.
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Souza, Cármino Antonio de. "Age and cytogenetic abnormalities." Hematology, Transfusion and Cell Therapy 40, no. 3 (July 2018): 199. http://dx.doi.org/10.1016/j.htct.2018.01.004.
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Quessada, Julie, Wendy Cuccuini, Paul Saultier, Marie Loosveld, Christine J. Harrison, and Marina Lafage-Pochitaloff. "Cytogenetics of Pediatric Acute Myeloid Leukemia: A Review of the Current Knowledge." Genes 12, no. 6 (June 17, 2021): 924. http://dx.doi.org/10.3390/genes12060924.
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Pediatric acute myeloid leukemia is a rare and heterogeneous disease in relation to morphology, immunophenotyping, germline and somatic cytogenetic and genetic abnormalities. Over recent decades, outcomes have greatly improved, although survival rates remain around 70% and the relapse rate is high, at around 30%. Cytogenetics is an important factor for diagnosis and indication of prognosis. The main cytogenetic abnormalities are referenced in the current WHO classification of acute myeloid leukemia, where there is an indication for risk-adapted therapy. The aim of this article is to provide an updated review of cytogenetics in pediatric AML, describing well-known WHO entities, as well as new subgroups and germline mutations with therapeutic implications. We describe the main chromosomal abnormalities, their frequency according to age and AML subtypes, and their prognostic relevance within current therapeutic protocols. We focus on de novo AML and on cytogenetic diagnosis, including the practical difficulties encountered, based on the most recent hematological and cytogenetic recommendations.
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Tamkus, Deimante, Ahmad Jajeh, Ebenezer Berko, David Osafo, Decebal Griza, Paula Kovarik, and Rose Catchatourian. "Adult Acute Lymphoblastic Leukemia and Cytogenetic Abnormalities in Different Racial and Ethnic Subgroups." Blood 106, no. 11 (November 16, 2005): 4547. http://dx.doi.org/10.1182/blood.v106.11.4547.4547.
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Abstract Inferior survival of African American and Hispanic patients with acute lymphoblastic leukemia (ALL) has been reported. The reason for this is unclear. A retrospective analysis was conducted to see if abnormal cytogenetics account for the differences. We have analyzed cytogenetic studies of 39 adults (16 year and older) with newly diagnosed ALL who were consecutively treated at John Stroger Hospital of Cook County between 1997 and 2005. The study population included 13 (33%) African Americans, 18 (46%) Hispanics, 6 (16%) Caucasians, and 2 (5 %) other ethnic background adults. Male to female ratio was 2:1. Mean age at diagnosis was 26 (range between 16 and 71 years). A clonal cytogenetic abnormality was detected in 27 patients, and 12 patients had normal karyotype. Patients with t (9;22)(q34;q11), BCR-ABL + by FISH, t (4;11)(q21;q23), +8, −7 cytogenetic abnormalities were assigned to an unfavorable cytogenetic group. This group was composed of 14 patients. None of our study patients had favorable cytogenetics: del (12p), t(12p), t(14q11-q23), inv(14)(q11;q32) or t(10;14)(q24;q11). Remaining 25 patients with normal karyotype (n=12) or miscellaneous cytogenetic abnormalities (n=13) were classified as normal risk group. 54 % of African Americans had unfavorable cytogenetics, compared with 33 % Caucasians and 17 % Hispanics. Translocation t (9;22) alone or in association with other cytogenetic abnormalities was most commonly seen. 9 patients had single, and 18 had multiple chromosomal changes. Hispanic group had more complex cytogenetic changes when compared with the African American or Caucasian groups. Unfavorable cytogenetic abnormalities may account for inferior survival in African Americans, but other factors such as compliance or pharmacogenetics should be evaluated, especially in the Hispanic patient population.
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Tam, Constantine S., Lynne V. Abruzzo, Katherine I. Lin, Jorge Cortes, Alice Lynn, Michael J. Keating, Deborah A. Thomas, Sherry Pierce, Hagop Kantarjian, and Srdan Verstovsek. "The role of cytogenetic abnormalities as a prognostic marker in primary myelofibrosis: applicability at the time of diagnosis and later during disease course." Blood 113, no. 18 (April 30, 2009): 4171–78. http://dx.doi.org/10.1182/blood-2008-09-178541.
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Abstract Although cytogenetic abnormalities are important prognostic factors in myeloid malignancies, they are not included in current prognostic scores for primary myelofibrosis (PMF). To determine their relevance in PMF, we retrospectively examined the impact of cytogenetic abnormalities and karyotypic evolution on the outcome of 256 patients. Baseline cytogenetic status impacted significantly on survival: patients with favorable abnormalities (sole deletions in 13q or 20q, or trisomy 9 ± one other abnormality) had survivals similar to those with normal diploid karyotypes (median, 63 and 46 months, respectively), whereas patients with unfavorable abnormalities (rearrangement of chromosome 5 or 7, or ≥ 3 abnormalities) had a poor median survival of 15 months. Patients with abnormalities of chromosome 17 had a median survival of only 5 months. A model containing karyotypic abnormalities, hemoglobin, platelet count, and performance status effectively risk-stratified patients at initial evaluation. Among 73 patients assessable for clonal evolution during stable chronic phase, those who developed unfavorable or chromosome 17 abnormalities had median survivals of 18 and 9 months, respectively, suggesting the potential role of cytogenetics as a risk factor applicable at any time in the disease course. Dynamic prognostic significance of cytogenetic abnormalities in PMF should be further prospectively evaluated.
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Strand, Jacob J., Terra L. Lasho, Susan M. Schwager, Michelle M. Elliott, Chin-Yang Li, and Ayalew Tefferi. "Cytogenetic Profile, JAK2V617F Mutational Status, and Response to Drug Therapy in Myelofibrosis with Myeloid Metaplasia." Blood 106, no. 11 (November 16, 2005): 2591. http://dx.doi.org/10.1182/blood.v106.11.2591.2591.
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Abstract Background: One of the utilities of molecular markers in hematological malignancies is their potential to predict response to drug therapy. Accordingly, we inquired about the effect of both cytogenetic profile and JAK2V617F mutational status on drug therapy response in myelofibrosis with myeloid metaplasia (MMM). Methods: Mutation analysis for JAK2V617 was performed in DNA derived from peripheral blood mononuclear cells, granulocytes, or both. Genomic DNA was amplified by PCR and fluorescent dye chemistry sequencing was performed using the same primers used for amplification (Levin et al. Cancer Cell2005;7:387). Abnormal cytogenetic findings were considered to be either favorable (sole 13q- or 20q- abnormalities) or unfavorable (other abnormalities) (Tefferi et al. BJH2001;113:763). Results: i. Patients and treatment: A total of 69 patients with MMM (median age 62 years, range 38–75; 47 males) received the following drugs as first-line therapy for either anemia or symptomatic splenomegaly; erythropoietin (Epo) alone or in combination with hydroxyurea (n=25), hydroxyurea alone (HU; n=17), interferon alpha (IFN; n=11), combination of thalidomide and prednisone (ThalPred; n=7), androgen preparations (Andro; n=5), and etanercept (n=4). ii. Results of cytogenetic studies and JAK2 mutation screening: Cytogenetic findings were abnormal in 35 patients (51%); favorable in 9 and unfavorable in 26. JAK2V617 mutation analysis revealed wild-type allele in 31 patients (45%) and either heterozygous (n=31) or homozygous (n=7) mutation in the remaining 38 patients (55%). iii. Correlation of response to cytogenetic/molecular markers: Overall, 17 patients (25%) achieved either a major (n=8) or minor (n=9) response in anemia from treatment with one of the aforementioned drugs. Regardless of either JAK2V617 mutational status or cytogenetic profile, treatment-induced responses in anemia were poor for IFN (0%) and HU (12%). In contrast, the best anemia responses were documented for ThalPred (57%), Andro (40%), and Epo-based therapy (32%). Among the 25 patients that received Epo-based therapy, all 3 patients with favorable cytogenetic abnormalities achieved major responses in anemia whereas such responses were seen in none of the 9 patients with unfavorable cytogenetic abnormalities and only 1 of 13 patients with normal cytogenetics (p=0.004). Furthermore, 3 of the 4 major responders were heterozygous for JAK2V617 and one carried the wild-type allele. In contrast, none of the 3 JAK2V617 homozygotes showed any type of response but all 3 also displayed unfavorable cytogenetics. None of the 7 ThalPred-treated patients carried favorable cytogenetics and yet 3 achieved major responses including one with unfavorable cytogenetics. JAK2V617 mutational status was heterozygous in 1 and wild-type in the other two. There were no major responses among the 5 Andro-treated patients despite the presence of favorable cytogenetic abnormalities in 2 patients. In order to investigate the relationship between cytogenetic profile and JAK2V617 mutational status further, we referred to an expanded database of 116 patients and found the incidence of unfavorable cytogenetics to be higher in JAK2V617 homozygotes compared to non-homozygotes (57% vs. 31%; p=0.16) Conclusion: The current study suggests clustering of favorable cytogenetic abnormalities in MMM with anemia response to Epo therapy and unfavorable cytogenetic abnormalities with homozygosity for JAK2V617 mutation.
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Wolanskyj, Alexandra P., Naseema Gangat, Susan M. Schwager, Rhett P. Ketterling, and Ayalew Tefferi. "Cytogenetic Abnormalities in Essential Thrombocythemia: Prevalence and Prognostic Significance." Blood 108, no. 11 (November 16, 2006): 3626. http://dx.doi.org/10.1182/blood.v108.11.3626.3626.
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Abstract Objectives: We conducted a study to describe the cytogenetic findings as well as clinical correlates and long-term prognostic relevance of abnormal cytogenetics at the time of diagnosis of Essential thrombocythemia (ET), in terms of clinical presentation, disease transformation into more aggressive myeloid disorders, and life expectancy. Patients and Methods: The study cohort consisted of a consecutive group of patients with ET who fulfilled the World Health Organization (WHO) diagnostic criteria, in whom bone marrow biopsy was performed at diagnosis, with interpretable cytogenetic analysis obtained in all cases. Results: A total of 403 patients were studied (median age, 56 years; median follow-up 64 months). The prevalence of abnormal cytogenetics at presentation was 6.7 % (27 of 403). The most common cytogenetic anomalies identified included trisomy 9 (4 patients), trisomy 8 (3 patients) and deletion 20q (3 patients). Parameters at diagnosis that were significantly associated with abnormal cytogenetics included palpable splenomegaly (p=0.03), current tobacco use (p=0.04); venous thrombosis (p= 0.019), extreme thrombocytosis (i.e., platelet count >1500 × 109/L, p = 0.03) and anemia with a hemoglobin of less than 10 g/dl (p=0.02); but did not include Jak2 mutation status, nor advanced age (≥ 60 years). During follow up, patients with abnormal cytogenetics were more likely to experience venous thrombosis (p=0.02) but not shorter survival [figure 1], transformation to AML, MDS or MMM, nor a greater requirement for cytotoxic therapy. Conclusion: Cytogenetic anomalies at presentation are relatively uncommon in ET, and do not predict a greater predilection towards evolution into more aggressive myeloid disorders, nor inferior survival. Fig. 1 Overall Survival According to Normal vs Abnormal Karyotype Fig. 1. Overall Survival According to Normal vs Abnormal Karyotype
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Klamova, Hana, Jana Brezinova, Kyra Michalova, Zuzana Zemanova, and Marek Trneny. "Cytogenetic Clonal Evolution in Chronic Myeloid Leukemia during Imatinib Mesylate Treatment." Blood 106, no. 11 (November 16, 2005): 4844. http://dx.doi.org/10.1182/blood.v106.11.4844.4844.
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Abstract Cytogenetic clonal evolution (CE) - the presence of cytogenetic abnormalities in addition to the Ph chromosome in chronic myeloid leukemia (Ph+ CML) is a known poor prognostic factor associated with disease progression. Occurence of additional cytogenetic abnormalities in both Ph positive and Ph negative mitoses was also described in imatinib treated CML patients and was associated with occuring therapy resistance. The long - term significance is so far poorly understood. Objective. To monitor cytogenetic abnormalities in chronic phase CML patients on imatinib treatment, following long-term interferon alfa (IFN) or hydroxyurea treatment. To compare the haematological disease progression in patients with or without cytogenetic evolution Patients and methods: Cytogenetic evolution was analyzed in 57 patients (median age 56, range 18–73) treated with imatinib in chronic phase, following interferon resistance or intolerance. The duration of IFN application was 22 months (range 3 – 46 months), duration of imatinib treatment was 16 months (range 6 – 55 months). Cytogenetic abnormalities were detected by conventional cytogenetics - caryotype analysis and fluorescence in situ hybridisation (FISH). Results: Complete cytogenetic remission was accomplished in 55 of 57 pts (96%) on imatinib, significant or complete cytogenetic response was observed in 36 of 57 patients (66%). Cytogenetic evolution was observed in 11 patients (19%) treated with imatinib: in the Ph+ clone (9 cases) and in the Ph− clone (2 cases). Median duration of imatinib treatment before the CE identification was 16 months (range 7–36 months). The most common additional abnormality was trisomy 8 (8 pts), second Ph chromosome (4 pts), and del (17) (4 pts). In 5 cases we observed the simultaneous occurence of two different cytogenetic abnormalities. Haematological progression was observed in 7 of 11 patients (63%) following 2 – 22 months imatinib treatment (median 9 months). 5 pts (46%) exited. Six patients live 8–22 months from the detection of cytogenetic evolution. Secondary malignancy was diagnosed in 1 patient. In the group of patients without cytogenetic evolution haematological progression was observed only in 9 of 46 (19.5%) cases, 4 patients died (14.3%). Conclusion: The role of IM concerning the cytogenetic evolution occurence in CML patients is not so far clear, the suppression of the Ph+ clone could enhance the proliferation of resistant ones. In our group of patients CE was documented in 11 patients (19%), in both Ph+ and Ph− cells. Significantly higher was the risk of haematological progression. CML patients treated with imatinib should be regularly monitored with conventional cytogenetic techniques, not only to follow the decrease in the proportion of Ph-positive cells, but also to look for new especially Ph-negative clonal chromosomal abnormalities. A longer follow-up time and systematic monitoring of cytogenetics is needed to establish the prognostic impact of clonal evolution in CML patients treated with imatinib.
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Najfeld, Vesna, Joseph Tripodi, Marina Kremanskaya, John Mascarenhas, and Ronald Hoffman. "Peripheral Blood Karyotyping Is Superior To Bone Marrow and Identifies Most Frequent Structural Chromosomal Rearrangements In Myelofibrosis." Blood 122, no. 21 (November 15, 2013): 3727. http://dx.doi.org/10.1182/blood.v122.21.3727.3727.
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Abstract In the past cytogenetic studies of patients with MF were hindered because marrow (BM) specimens were used for karyotyping but frequently could not be obtained due to advanced marrow fibrosis. Since MF is characterized by the constitutive mobilization of immature myeloid cells into the peripheral blood (PB), we compared unstimulated PB specimens with BM specimens to determine their utility in successfully detecting cytogenetic abnormalities in patients with MF. We also simultaneously performed interphase FISH (IFISH) studies in order to determine if IFISH identified additional genomic abnormalities in MF. We evaluated 183 patients who had had successful conventional and molecular cytogenetic analyses. Our myeloproliferative neoplasm ( MPN)-FISH panel consisted of twelve probes (EGR1 at 5q31, D5S23 at 5p15.3, D7Z1 at 7p11-q11, D7S522 at 7q31, D8Z2 at 8p11-q11, CDKN2A at 9p21, CEP9 at 9p11-q11, ATM at 11q22,1, Rb1 at 13q14, and D20S18 at 20q12, CKS1B at 1q21 and CDKN2C at 1p32). BM cytogenetics was studied in 60 pts (33%) and PB cytogenetics were evaluated in 123 pts (67%). Conventional cytogenetics was informative for 96% (123/128) of PB specimens and 97% (60/62) of BM samples. When conventional cytogenetic analysis was compared to IFISH, concordant results were observed in 154 patients (84%). Moreover, conventional karyotyping identified chromosomal abnormalities in an additional 18 patients (10%), which were not targeted by the 12 loci FISH panel. Among these patients, structural abnormalities of chromosome 12 were detected in 6 patients (33%) which represents the most frequent structural abnormality detected in MF and was associated with poor survival. Of the 63 patients with concordant abnormal cytogenetics and FISH the most frequent abnormalities included: del(20)(q11q13) (n=30, 48%), unbalanced 1q translocations resulting in trisomy 1q or duplication of 1q (n=17, 27%), gain of chromosome 8 (n=9, 14%), +8,+9( n=4, 6%), trisomy 9 (n=4, 6%), del(7q)/-7( n=7,11%), deletion 13q (n=9,14%) and complex karyotype (n=16, 25%). The remaining 11pts (6%) had discordant conventional and molecular cytogenetic results and were divided into two categories: A) those with normal cytogenetics (with or without non clonal abnormalities) and an abnormal MPN IFISH panel and B) those with abnormal clonal karyotype with normal lFISH. When compared to BM, PB specimens had a similar rate of abnormal karyotype: 51% in PB vs 48% in BM. Our results unequivocally demonstrated that conventional cytogenetics of MF can be successfully obtained from unstimulated PB specimens in 96% of patients and that analysis of BM does not reveal additional cytogenetic abnormalities. We conclude that FISH analysis has limited value in MF and is only informative for those patients who lack mitotic cells or who are cytogenetically normal, and in these patients, IFISH detects cryptic abnormalities in 4%. Use of PB karyotyping in MF is sufficient to effectively detects clonal hematopoiesis which contributes to prognostic risk stratification and influences therapeutic decision making. Disclosures: No relevant conflicts of interest to declare.
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Rai, Vandana. "Autism Genetics and Cytogenetic Abnormalities." Trends in Molecular Sciences 3, no. 1 (January 1, 2011): 1–13. http://dx.doi.org/10.3923/tms.2011.1.13.
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Taniwaki, Masafumi. "3. Cytogenetic and Molecular Abnormalities." Nihon Naika Gakkai Zasshi 100, no. 7 (2011): 1801–6. http://dx.doi.org/10.2169/naika.100.1801.
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Fonseca, Rafael, Lionel J. A. Coignet, and Gordon W. Dewald. "CYTOGENETIC ABNORMALITIES IN MULTIPLE MYELOMA." Hematology/Oncology Clinics of North America 13, no. 6 (December 1999): 1169–80. http://dx.doi.org/10.1016/s0889-8588(05)70119-2.
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Stratton, M. R., J. Darling, P. L. Lantos, C. S. Cooper, and B. R. Reeves. "Cytogenetic abnormalities in human ependymomas." International Journal of Cancer 44, no. 4 (October 15, 1989): 579–81. http://dx.doi.org/10.1002/ijc.2910440403.
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Antonini, P., A. M. Vénuat, G. Linares, B. Caillou, M. Schlumberger, J. P. Travagli, R. Berger, and C. Parmentier. "Cytogenetic abnormalities in thyroid adenomas." Cancer Genetics and Cytogenetics 52, no. 2 (April 1991): 157–64. http://dx.doi.org/10.1016/0165-4608(91)90458-7.
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Nilbert, Mef, Nils Mandahl, Sverre Heim, Anders Rydholm, Helena Willén, and Felix Mitelman. "Cytogenetic abnormalities in an angioleiomyoma." Cancer Genetics and Cytogenetics 37, no. 1 (January 1989): 61–64. http://dx.doi.org/10.1016/0165-4608(89)90075-7.
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Dobin, S., J. Reynolds, R. F. Peterson, R. C. Klugo, and K. Scott Coffield. "47 Cytogenetic abnormalities in oncocytomas." Cancer Genetics and Cytogenetics 28, no. 1 (September 1987): 41. http://dx.doi.org/10.1016/0165-4608(87)90326-8.
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Belkady, Boutaina, Rachida Cadi, Sanaa Nassereddine, and Abdelhamid Barakat. "Intellectual disability and cytogenetic abnormalities." IBRO Reports 6 (September 2019): S373—S374. http://dx.doi.org/10.1016/j.ibror.2019.07.1187.
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Li, Ruzhong, David M. Stelly, and Norma L. Trolinder. "Cytogenetic abnormalities in cotton (Gossypium hirsutum L.) cell cultures." Genome 32, no. 6 (December 1, 1989): 1128–34. http://dx.doi.org/10.1139/g89-566.
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High frequencies of somaclonal phenotypic and cytogenetic variation have been observed previously among regenerants from cotton (Gossypium hirsutum L., 2n = 4x = 52). In this study we endeavored to determine if cytogenetic abnormalities would be detectable in cotton cell cultures and if so, whether or not the observed abnormalities would parallel those expected on the basis of previous cytogenetic analyses of cotton somaclones. Paired samples from suspension cultures established from 21-month-old 'Coker 312' and 8-month-old 'Coker 315' calli were pretreated or not pretreated with colchicine to detect cytogenetic abnormalities at metaphase or anaphase–telophase, respectively. Cell cultures established from both calli were found to vary in chromosome number. Hypoaneuploidy was common, but hyperaneuploidy and polyploidy were rare. Modal chromosome numbers for the 'Coker 312' and 'Coker 315' cultures were 46 and 50, respectively. Bridges at anaphase and telophase were frequent in the 'Coker 312' cultures but rare in the 'Coker 315'cultures. Cytogenetic differences between the cultures could be due to effects of culture age, genotype, their interaction, or other factors. Very small chromosomes, presumably centric fragments, as well as ring chromosomes and putative bridges between metaphase chromosomes occurred at low frequencies. The prevalence of hypoaneuploidy and rarity of hyperaneuploidy and polyploidy in cultures paralleled previous results on cotton somaclones, indicating that cytogenetic abnormalities arising in vitro probably contribute significantly to cotton somaclonal variation. The occurrence of hypoaneuploidy and bridges, including multiple bridges within single cells, is concordant with the hypothesis that breakage–fusion–bridge cycles may accumulate during in vitro culture of cotton.Key words: cotton, Gossypium, tissue culture, cytogenetics.
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Sonneveld, Pieter, Hervé Avet-Loiseau, Sagar Lonial, Saad Usmani, David Siegel, Kenneth C. Anderson, Wee-Joo Chng, et al. "Treatment of multiple myeloma with high-risk cytogenetics: a consensus of the International Myeloma Working Group." Blood 127, no. 24 (June 16, 2016): 2955–62. http://dx.doi.org/10.1182/blood-2016-01-631200.
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AbstractThe International Myeloma Working Group consensus updates the definition for high-risk (HR) multiple myeloma based on cytogenetics Several cytogenetic abnormalities such as t(4;14), del(17/17p), t(14;16), t(14;20), nonhyperdiploidy, and gain(1q) were identified that confer poor prognosis. The prognosis of patients showing these abnormalities may vary with the choice of therapy. Treatment strategies have shown promise for HR cytogenetic diseases, such as proteasome inhibition in combination with lenalidomide/pomalidomide, double autologous stem cell transplant plus bortezomib, or combination of immunotherapy with lenalidomide or pomalidomide. Careful analysis of cytogenetic subgroups in trials comparing different treatments remains an important goal. Cross-trial comparisons may provide insight into the effect of new drugs in patients with cytogenetic abnormalities. However, to achieve this, consensus on definitions of analytical techniques, proportion of abnormal cells, and treatment regimens is needed. Based on data available today, bortezomib and carfilzomib treatment appear to improve complete response, progression-free survival, and overall survival in t(4;14) and del(17/17p), whereas lenalidomide may be associated with improved progression-free survival in t(4;14) and del(17/17p). Patients with multiple adverse cytogenetic abnormalities do not benefit from these agents. FISH data are implemented in the revised International Staging System for risk stratification.
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Breems, Dimitri A., Wim L. J. Van Putten, Georgine E. De Greef, Shama L. Van Zelderen-Bhola, Klasien B. J. Gerssen-Schoorl, Clemens H. M. Mellink, Aggie Nieuwint, et al. "Monosomal Karyotype in Acute Myeloid Leukemia: A Better Indicator of Poor Prognosis Than a Complex Karyotype." Journal of Clinical Oncology 26, no. 29 (October 10, 2008): 4791–97. http://dx.doi.org/10.1200/jco.2008.16.0259.
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Purpose To investigate the prognostic value of various cytogenetic components of a complex karyotype in acute myeloid leukemia (AML). Patients and Methods Cytogenetics and overall survival (OS) were analyzed in 1,975 AML patients age 15 to 60 years. Results Besides AML with normal cytogenetics (CN) and core binding factor (CBF) abnormalities, we distinguished 733 patients with cytogenetic abnormalities. Among the latter subgroup, loss of a single chromosome (n = 109) conferred negative prognostic impact (4-year OS, 12%; poor outcome). Loss of chromosome 7 was most common, but outcome of AML patients with single monosomy −7 (n = 63; 4-year OS, 13%) and other single autosomal monosomies (n = 46; 4-year OS, 12%) did not differ. Structural chromosomal abnormalities influenced prognosis only in association with a single autosomal monosomy (4-year OS, 4% for very poor v 24% for poor). We derived a monosomal karyotype (MK) as a predictor for very poor prognosis of AML that refers to two or more distinct autosomal chromosome monosomies (n = 116; 4-year OS, 3%) or one single autosomal monosomy in the presence of structural abnormalities (n = 68; 4-year OS, 4%). In direct comparisons, MK provides significantly better prognostic prediction than the traditionally defined complex karyotype, which considers any three or more or five or more clonal cytogenetic abnormalities, and also than various individual specific cytogenetic abnormalities (eg, del[5q], inv[3]/t[3;3]) associated with very poor outcome. Conclusion MK enables (in addition to CN and CBF) the prognostic classification of two new aggregates of cytogenetically abnormal AML, the unfavorable risk MK-negative category (4-year OS, 26% ± 2%) and the highly unfavorable risk MK-positive category (4-year OS, 4% ± 1%).
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Farag, Sherif S., Kellie J. Archer, Krzysztof Mrózek, James W. Vardiman, Andrew J. Carroll, Mark J. Pettenati, Bayard L. Powell, et al. "Pre-Treatment Cytogenetics Predict Complete Remission and Long-Term Outcome in Patients (Pts) ≥60 Years with Acute Myeloid Leukemia (AML): Results from Cancer and Leukemia Group B (CALGB) 8461." Blood 104, no. 11 (November 16, 2004): 568. http://dx.doi.org/10.1182/blood.v104.11.568.568.
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Abstract Previous studies have identified broad cytogenetic risk groups in AML, by comparing outcome of pts with different recurring abnormalities, using cytogenetically normal pts as the reference group. Pts with better survival were considered as “favorable”, and those with worse outcome as “unfavorable” risk. To identify prognostic cytogenetic groups for complete remission (CR) and overall survival (OS), without the selection of a reference group, we used classification trees and tree-structured survival analysis (TSSA). We analyzed the outcome of 600 AML pts ≥60 years (yrs), enrolled in the prospective CALGB cytogenetic study 8461 and treated on CALGB front-line AML protocols. Analysis was restricted to cytogenetic aberrations occuring in ≥5 pts. Once prognostic cytogenetic abnormalities for CR and OS were identified, multivariable models were constructed. Median age was 68 (range, 60–86) yrs, and 98% had de novo AML. The most common karyotypes were normal (46%), complex with ≥3 abnormalities (complex ≥3, 19%), and ≥5 abnormalities (complex ≥5, 14%). Core binding factor (CBF) abnormalities, ie, inv(16) and t(8;21), occurred in 5%. Overall, 49.5% of pts achieved CR with only 7% (95%CI: 5%–9%) alive at 5 yrs. Table 1 shows prognostic cytogenetic risk groups identified by classification trees and TSSA for CR and OS, respectively. Table 1: Prognostic Cytogenetic Groups by Tree Analysis CR OS Risk group CR rate Risk group 5-yr OS (95% CI) *P<0.05 compared to CBF; CI, confidence interval Complex≥3 30%* CBF 20 (6–20)% Abnormal, non CBF 46%* <5 abnormalities without CBF or −7 8 (5–10)% Normal 57% Complex≥5 0% CBF 75% −7 0% Table 2 shows the multivariable analyses adjusting for other baseline clinical variables. Only lower % circulating blasts (P=0.0002) and cytogenetic risk groups (P<0.0001) predicted CR. Compared to CBF pts, the odds of CR were significantly lower for pts with complex ≥3 and abnormal, non-CBF karyotypes, whereas the odds of CR for cytogenetically normal pts was not significantly different from CBF pts. For OS, cytogenetic risk groups (P<0.0001), older age (P=0.03), and higher WBC at diagnosis (P=0.02) predicted shorter survival. Compared to CBF pts, the risk of death was significantly higher for those with complex ≥5 karyotype, −7, and <5 abnormalities without CBF or −7. Table 2: Multivariable Analyses CR OS Significant Variables OR (95% CI) Significant Variables HR (95% CI) *CBF is the reference group; OR, odds ratio of achieving CR; HR, hazard ratio of death; CI, confidence interval % circulating blasts 0.90 (0.84–0.95) Age 1.28 (1.09–1.50) Cytogenetics group* WBC 1.03 (1.01–1.04) Complex≥3 0.12 (0.05–0.33) Cytogenetics group* Abnormal, non CBF 0.26 (0.10–0.65) Complex≥5 4.53 (2.80–7.32) Normal 0.44 (0.18–1.09) −7 2.57 (1.39–4.76) <5 abnormalities without CBF or −7 1.62 (1.07–2.46) We conclude that pre-treatment cytogenetics are predictive of CR and OS of older AML pts, particularly identifying pts with complex ≥5 karyotype and −7, who benefit minimally if at all from standard chemotherapy. Such pts may be better suited for investigational therapy or only supportive care.
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Chen, Yiming, Jorge Cortes, Zeev Estrov, Stefan Faderl, Wei Qiao, Lynne Abruzzo, Guillermo Garcia-Manero, et al. "Persistence of Cytogenetic Abnormalities at Complete Remission After Induction in Patients With Acute Myeloid Leukemia: Prognostic Significance and the Potential Role of Allogeneic Stem-Cell Transplantation." Journal of Clinical Oncology 29, no. 18 (June 20, 2011): 2507–13. http://dx.doi.org/10.1200/jco.2010.34.2873.
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Purpose To determine the prognostic impact of persistent cytogenetic abnormalities at complete remission (CR) on relapse-free survival (RFS) and overall survival (OS) in patients with acute myeloid leukemia (AML) and to examine the potential role of allogeneic stem-cell transplantation (SCT) in this setting. Patients and Methods Data from 254 adult patients with AML (excluding acute promyelocytic leukemia) who achieved CR after induction chemotherapy on various first-line protocols were examined. Results Median follow-up for surviving patients was 43 months. Patients with cytogenetic abnormalities at CR (n = 71) had significantly shorter RFS (P = .001) and OS (P < .001) compared with patients with normal cytogenetics at CR (n = 183); 3-year RFS was 15% and 45%, and 3-year OS was 15% and 56%, respectively. Among the patients with persistent cytogenetic abnormalities at CR, those who underwent SCT in first CR (CR1; n = 15) had better RFS and OS compared to those without SCT (n = 56; P = .04 and .06, respectively). In multivariate analysis, persistent cytogenetic abnormalities at CR was an independent predictor for RFS (P < .001) and OS (P = .001), but among patients with persistent cytogenetic abnormalities at CR, no significant differences in OS (P = .25) was observed between those who did or did not receive SCT with a trend favoring SCT for RFS (P = .08). Conclusion Persistent cytogenetically abnormal cells at CR predict a significantly shorter RFS and OS. SCT in CR1 may improve the clinical outcome of patients lacking cytogenetic remission after induction although this depends on patient selection.
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Borthakur, Gautam, Constantine Tam, Hagop Kantarjian, E. Lin, Jorge Cortes, Susan O’Brien, Charles Koller, Sherry Pierce, and Michael Keating. "Chromosome 17 Abnormalities Are Associated with Worse Overall and Relapse Free Survival in Patients with Acute Myelogenous Leukemia and Poor-Risk Cytogenetics." Blood 112, no. 11 (November 16, 2008): 1501. http://dx.doi.org/10.1182/blood.v112.11.1501.1501.
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Abstract Purpose: Chromosome 17 abnormalities define a group of patients with acute myelogenous leukemia (AML) (Nahi, H. et al. Leukemia and Lymphoma2008;49:508) with poor outcomes. We analyzed the additional impact of chromosome 17 abnormalities (−17, −17p, −17q, der17) among patients with AML and cytogenetic abnormalities traditionally considered to be of adverse prognosis. Patients and Methods: 1086 patients with AML [excluding inv 16, t (8;21), t (15;17), Diploid/-y abnormality] were included in this analysis. Based on cytogenetic abnormalities patients were grouped into: −5,−7,−5and −7, complex. The following parameters were included in uni and multi-variate analysis: age, performance status, WBC, hemoglobin, platelets, marrow blast percentage, bilirubin, creatinine, albumin, LDH, chromosome 17 abnormality (yes/no). Results: Four hundred and fourteen (45%) patients achieved complete remission (CR) or CR with incomplete platelet recovery (CRp) and 267 (64.5%) patients relapsed. Two hundred seventy (24.9%) patients had abnormalities of chromosome 17. Abnormalities of chromosome 17 were associated with lower CR or CRp rate (p=0.02) and higher possibility of having cytogenetic abnormality of −5 or −7 (p<0.0001). Multivariate analysis showed that patients with abnormalities of chromosome 17 had worse overall survival (OS) compared to patients without (p= 0.003)(Fig.1). Multi-variate analysis within cytogenetic subgroups showed that chromosome 17 abnormalities were associated with worse OS in patients with chromosome 5 abnormality(p=.02) (data not shown) and in those with complex cytogenetics (p=.04)(Fig.2) and not in patients with chromosome 7 (p=.17)or combined 5 and 7 abnormalities (p=.33). Similar analysis restricted to patients achieving CR/CRp after induction therapy showed that impact of chromosome 17 abnormalities on relapse free survival (RFS) mirrored their impact on OS. Conclusion: chromosome 17 abnormalities are associated with worse OS and RFS in patients with AML and adverse cytogenetics and have additional negative impact on the outcomes in certain well-known adverse cytogenetic subgroups. Figure 1: Kaplan-Meier estimates of overall survival by status of chromosome 17 Figure 1:. Kaplan-Meier estimates of overall survival by status of chromosome 17 Figure 2: Kaplan-Meier estimates of overall survival by status of chromosome 17 in subgroup of patient, complex Figure 2:. Kaplan-Meier estimates of overall survival by status of chromosome 17 in subgroup of patient, complex
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Kuykendall, Andrew, Chetasi Talati, Najla H. Al Ali, Eric Padron, David Sallman, Jeffrey E. Lancet, Kendra L. Sweet, Alan F. List, Kenneth S. Zuckerman, and Rami S. Komrokji. "Characterization of Cytogenetic Abnormalities in Myelofibrosis and Relationship to Clinical Outcome." Blood 128, no. 22 (December 2, 2016): 1937. http://dx.doi.org/10.1182/blood.v128.22.1937.1937.
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Abstract Introduction: Cytogenetic abnormalities occur frequently in patients with myelofibrosis (MF) and carry significant prognostic value. A variety of cytogenetic abnormalities have been reported with variable incidence. While the prognostic significance of more common cytogenetic abnormalities is well documented, the prognostic significance of less common abnormalities are difficult to discern due to limiting cohort size. Further, the specific phenotype associated with various cytogenetic abnormalities is less clear. We reviewed our institutional experience in an effort to describe the spectrum of chromosomal abnormalities, assess their correlation with clinical features, and validate their prognostic impact in a cohort of MF patients. Methods: This was a single institution, retrospective study of all patients with a diagnosis of MF who were seen at our center between 2/2001 - 6/2016.We reviewed cases of myelofibrosis in the Moffitt Cancer Center database. Definitions of primary myelofibrosis (PMF), post-essential thrombocythemia myelofibrosis (post-ET MF) and post-polycythemia vera myelofibrosis (post-PV MF) were according to World Health Organization 2016 criteria and the International Working Group for Myeloproliferative Neoplasms, Research and Treatment, respectively. Cytogenetic analysis was documented with preference to date of diagnosis. Overall survival was measured from time of cytogenetic analysis. Results: We identified 312 eligible. Cytogenetic data were available in 278 of 312 (89%) patients. The cohort was 59% male with a median age of 70 years at time of first presentation. PMF comprised 76% of cases with post-PV MF and post-ET MF accounting for 9% and 15% of cases respectively. Cytogenetic analysis was performed within 3 months of diagnosis in 63% and over a year after diagnosis in 24% of patients. Cytogenetic spectrum and frequency is shown in Figure 1. Normal diploid karyotype was present in 55%. The most common cytogenetic abnormality was a deletion of the long arm of chromosome 20 (del 20q), occurring in 39 (14%) cases. Del 20q occurred as an isolated abnormality in 26/39 cases. When occurring in conjunction with other structural abnormalities, it was most often associated with trisomy 9 (6/39). A deletion of the long arm of chromosome 13 (del 13q) was the second most common chromosomal aberration, occurring in 26 (9%) of cases and usually presenting as the sole abnormality (15/26). An extra copy of chromosome 8 (trisomy 8) occurred in 21 (8%) cases and often occurred in conjunction with other cytogenetic abnormalities (11/21). Less common cytogenetic abnormalities included trisomy 9, deletion 7q and deletion 5q, occurring in less than 4% of cases. Monosomal and complex karyotypes accounted for 10% and 8.3% of cytogenetics, respectively. We then assessed relationships between cytogenetic abnormalities and clinical and pathologic features. Del20q was associated with a lower IPSS score (r = -0.18, p = 0.0006). Deletion 13q was associated with older age at presentation (r = 0.14, p = 0.007). Prevalence of trisomy 8 was highest in post-polycythemia vera myelofibrosis (r = 0.14, p = 0.03) and associated with increased peripheral blast percentage (r = 0.16, p < 0.0001). Deletion 5q was associated with decreased hemoglobin (r = -0.13, p = 0.04), transfusion dependence (r = 0.20, p = 0.0009) and conversion to blast phase (r = 0.23, p = 0.0001). Patients with del 20q, del 13q, and trisomy 9 had median overall survival (OS) comparable to patients with a normal karyotype (45 vs 54 months, respectively, p = 0.69). Patients with unfavorable cytogenetic profiles (del 5q, trisomy 8, and chromosome 17 abnormalities) had significantly worse OS when compared to patients with normal diploid karyotype (20 vs 54 months, p = 0.0002) (figure 2). In multivariate regression analysis, controlling for DIPSS, deletion 5q (HR: 0.34 [0.15-0.78]; p = 0.01) and trisomy 8 (HR: 0.35 [0.17-0.73]; p = 0.005) were significantly associated with inferior overall survival. Conclusions: Cytogenetic abnormalities in myelofibrosis provide significant prognostic discrimination in patients with myelofibrosis. Our findings validate the prognostic value of cytogenetics and raise possible heretofore unrecognized clinical associations. Disclosures Lancet: Novartis: Consultancy; Biopath Holdings: Consultancy; Karyopharm: Consultancy; Boehringer-Ingelheim: Consultancy; Quantum First: Consultancy; ERYtech: Consultancy; Pfizer: Research Funding; Celgene: Consultancy, Research Funding; Jazz Pharmaceuticals: Consultancy; Seattle Genetics: Consultancy; Kalo Bios: Consultancy; Baxalta: Consultancy; Amgen: Consultancy. Sweet:Incyte Corporation: Research Funding; Pfizer: Speakers Bureau; Karyopharm: Honoraria, Research Funding; Ariad: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau. Komrokji:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Speakers Bureau.
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Woyach, Jennifer A., Amy S. Ruppert, Kristie A. Blum, Jeffrey Alan Jones, Joseph M. Flynn, Amy J. Johnson, Michael R. Grever, John C. Byrd, and Nyla A. Heerema. "Response, Progression-Free Survival, and Overall Survival of Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL) Treated with Flavopiridol: Impact of Poor Risk Cytogenetic Abnormalities." Blood 116, no. 21 (November 19, 2010): 2456. http://dx.doi.org/10.1182/blood.v116.21.2456.2456.
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Abstract Abstract 2456 The cyclin-dependent kinase inhibitor flavopiridol has been shown to be a highly effective therapy in patients (pts) with relapsed or refractory CLL, and we have shown in vitro that flavopiridol induces apoptosis independent of the p53 pathway. Here we analyze the results of two early single-agent flavopiridol trials at our institution, OSU 0055 and OSU 0491, to study the effect of poor risk cytogenetic abnormalities on overall response rate (ORR), progression-free survival (PFS) and overall survival (OS). 112 pts are included in this analysis; 49 from the phase I and 63 from the phase II study. Data from the two trials were combined for all analyses. Specific genetic abnormalities were identified by fluorescence in situ hybridization, and complexity was determined by stimulated karyotype analysis. Dohner's hierarchical classification was used to group the pts into those with del (17p), those with del (11q) and those with other cytogenetic abnormalities or normal cytogenetics. Using this classification, 40 pts (37%) had del (17p), 37 (33%) had del (11q), and 35 (31%) had neither of these abnormalities. These groups were not significantly different in terms of age, sex, Rai stage, or percent fludarabine-refractory. The median number of prior treatments was 4 (range 1–11) and did not differ among cytogenetic groups (p=0.21). The presence of bulky adenopathy (≥5 cm) was significantly different among the groups (p=0.01). 89% of pts with del (11q) had bulky disease, while only 60% with del (17p) and 77% of pts without these abnormalities had bulky disease. Complex cytogenetics (≥3 abnormalities) were much more likely in pts with del (17p), where 63% possessed a complex karyotype, as opposed to 32% of pts with del (11q) and 26% of pts with other abnormalities (p=0.003). The ORR was 47%, and was not significantly different among the cytogenetic groups (p=0.17). ORR for pts with del (17p) was 48%, for pts with del (11q) was 57%, and for those without these cytogenetic abnormalities was 34%. The overall median PFS was 10 months (mo.). While the estimated medians were slightly higher in pts with poor risk cytogenetics, 10 mo. for both del (17p) and del (11q) groups, and 8 mo. for pts without these abnormalities, the risk of progression changed significantly over time and by 24 mo., the estimated PFS for pts with del (17p), del (11q), and other cytogenetics was respectively, 4%, 5%, and 24%. Overall median OS was 28 mo. and was not significantly different among the groups (20 mo. for del (17p), 36 mo. for del (11q), and 26 mo. for pts without these abnormalities; p=0.13). Multivariable models were fit for ORR, PFS, and OS, which included cytogenetic group, treatment schedule, age, Rai stage, number of prior treatments, bulky adenopathy and presence of complex karyotype. With respect to ORR, odds of response were not significantly different among the cytogenetic groups (p=0.21), and notably, complex karyotype was not a significant predictor of ORR (p=0.15). Since similar patterns of PFS were observed for pts with del (17p) and del (11q), these groups were combined and the risk of progression relative to pts without these abnormalities were allowed to change over time. Although cytogenetic group was not statistically significant (p=0.07), it should be noted that the risk of progression tended to be lower for pts with del (17p)/del (11q) in the first six months and then increased with follow-up as compared to pts without these abnormalities (hazard ratio (HR) 0.7 at 3 mo., 1.1 at 6 mo., 1.5 at 12 mo. and 2.2 at 24 mo.). The only independent predictor of shorter PFS was the presence of bulky adenopathy (HR=2.0, 95% confidence interval (CI) 1.1–3.7). While some differences were observed in PFS, OS was not significantly different among the cytogenetic groups when controlling for other variables (p=0.24) but was impacted (p=0.005) by the number of prior treatments (HR=1.2, 95% CI 1.1–1.3). Collectively, these data show that pts with cytogenetically high-risk disease who are treated with flavopiridol have a high ORR that is not significantly different from those without these cytogenetic abnormalities. While there may be differences with respect to PFS that are being evaluated further, OS did not differ among cytogenetic groups. Flavopiridol is thus an attractive agent to study in the first-line setting for pts with poor-risk cytogenetic abnormalities, as well as to use in further single agent and combination studies in relapsed or refractory disease. Disclosures: Grever: Sanofi Aventis: Dr. Grever is on the use patent for flavopiridol. This patent has not been awarded and has no monetary value at this time. Byrd: Sanofi Aventis: Dr. Byrd is on the use patent for flavopiridol. This patent has not been awarded and has no monetary value at this time.
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Binder, Moritz, S. Vincent Rajkumar, Rhett P. Ketterling, Angela Dispenzieri, Martha Q. Lacy, Morie A. Gertz, Francis K. Buadi, et al. "Prognostic Implications of Multiple Cytogenetic High-Risk Abnormalities in Patients with Newly Diagnosed Multiple Myeloma." Blood 128, no. 22 (December 2, 2016): 5615. http://dx.doi.org/10.1182/blood.v128.22.5615.5615.
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Abstract Background: Cytogenetic evaluation using fluorescence in situ hybridization (FISH) at the time of diagnosis is essential for initial risk stratification in multiple myeloma. The presence of specific cytogenetic abnormalities is known to confer a poor prognosis, less is known about the cumulative effect of multiple cytogenetic high-risk abnormalities. We aimed to evaluate the prognostic implications of the presence of multiple cytogenetic high-risk abnormalities at the time of diagnosis. Methods: We studied 226 patients who were diagnosed with multiple myeloma between July 2004 and July 2014 at Mayo Clinic Rochester, underwent FISH evaluation within six months of diagnosis, and presented with cytogenetic high-risk abnormalities. High-risk cytogenetics were defined as t(4;14), t(14;16), t(14;20), del(17p), or gain(1q). Bone marrow aspirates were evaluated for deletions, monosomies, trisomies, and tetrasomies using chromosome- or centromere-specific FISH probes. IGH rearrangements were evaluated using an IGH break-apart probe and evaluating up to five potential partners (FGFR3, CCND1, CCND3, MAF, and MAFB). Kaplan-Meier overall survival estimates were calculated and the log-rank test was used to compare overall survival in patients with single and multiple cytogenetic high-risk abnormalities. A multivariable-adjusted Cox regression model was used to assess the effect of multiple cytogenetic high-risk abnormalities on overall survival adjusting for age, sex, and Revised International Staging System (R-ISS) stage. P-values below 0.05 were considered statistically significant. Results: The median age at diagnosis was 65 years (32 - 90), 129 (57%) of the patients were male. The median overall survival was 3.5 years (3.1 - 4.9) for the entire cohort (n = 226), 4.0 years (3.3 - 5.1) for those with one cytogenetic high-risk abnormality (n = 182, 80%), and 2.6 years (1.7 - 3.1) for those with two cytogenetic high-risk abnormalities (n = 44, 20%). There were no patients with more than two cytogenetic high-risk abnormalities. Ninety-eight patients (45%) had a high-risk translocation, 77 (35%) had del(17p), 39 (18%) had a high-risk translocation plus del(17p), and 5 (2%) had gain(1q) plus either a high-risk translocation or del(17p). Figure 1 shows the Kaplan-Meier overall survival estimates stratified by the number of cytogenetic high-risk abnormalities (n = 226). The presence of two cytogenetic high-risk abnormalities (compared to one) was of prognostic significance after adjusting for age, sex, and R-ISS stage (HR 2.01, 95% CI 1.27 - 3.19, p = 0.003, n = 205). Conclusions: Approximately one in five patients with newly diagnosed high-risk multiple myeloma presented with two high-risk abnormalities at the time of diagnosis. These patients experienced inferior overall survival suggesting a cumulative effect of multiple cytogenetic high-risk abnormalities. The relatively low number of observed gain(1q) was likely related to the fact that not all patients were evaluated for that abnormality. Therefore the presented hazard ratio represents a conservative effect estimate and may underestimate the true effect. Figure 1 Figure 1. Disclosures Dispenzieri: GSK: Membership on an entity's Board of Directors or advisory committees; Jannsen: Research Funding; Alnylam: Research Funding; Celgene: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Prothena: Membership on an entity's Board of Directors or advisory committees; pfizer: Research Funding. Kapoor:Takeda: Research Funding; Celgene: Research Funding; Amgen: Research Funding. Kumar:Janssen: Consultancy, Research Funding; BMS: Consultancy; AbbVie: Research Funding; Millennium: Consultancy, Research Funding; Onyx: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Sanofi: Consultancy, Research Funding; Skyline: Honoraria, Membership on an entity's Board of Directors or advisory committees; Array BioPharma: Consultancy, Research Funding; Noxxon Pharma: Consultancy, Research Funding; Kesios: Consultancy; Glycomimetics: Consultancy.
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Cerquozzi, Sonia, Daniela Barraco, Curtis A. Hanson, Rhett P. Ketterling, Animesh Pardanani, Naseema Gangat, and Ayalew Tefferi. "Abnormal Karyotype and Prognosis in Polycythemia Vera: A Single Center Experience in 239 Informative Cases." Blood 128, no. 22 (December 2, 2016): 3115. http://dx.doi.org/10.1182/blood.v128.22.3115.3115.
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Abstract Background In polycythemia vera (PV), abnormal karyotype at diagnosis has been reported in 10% to 20% of patients and some studies have suggested an association with inferior survival (Leukemia2013;27:1874) . In the current study, we examined the prognostic contribution of abnormal karyotype, in general, and specific abnormalities, in particular, in newly diagnosed PV. Methods Study patients were selected from our institutional database of myeloproliferative neoplasms (MPN) and fulfilled the 2008 World Health Organization (WHO) criteria for diagnosis of PV (Blood. 2009;114:937). Cytogenetic analysis and reporting was done according to the International System for Human Cytogenetic Nomenclature (Cytogenetic and Genome Research2013;141:1-6). Assignment as "unfavorable karyotype" was according to criteria established for PMF: favorable = normal + favorable abnormalities; unfavorable = unfavorable abnormalities (Leukemia. 2011;25:82). Screening for the two most frequent mutations in PV, other than JAK2 (i.e. TET2 and ASXL1), were performed according to conventional methods (Leukemia. 2014;28:2206). Statistical analyses considered clinical and laboratory parameters obtained at time of diagnosis. Results Patient characteristics: Median (range) values for the 239 study patients (53% females) included: age 62 (17-94), leukocyte count 11.7 x 10(9)/L (4.3-59.3) and platelet count 479 x 10(9)/L (37-2747). Palpable splenomegaly was present in 26% of the patients, pruritus in 27%, erythromelalgia in in 8%, hypertension in 47%, diabetes in 10% and hyperlipidemia in 28%. Thrombosis history at diagnosis was documented in 33% of the patients and 20% experienced the same after diagnosis. 73% of the patients were "high risk" by conventional risk stratification. Mutation screening for TET2 and ASXL1 was performed in 80 patients and mutational frequencies were 19% and 11% respectively. All study patients provided cytogenetic information, which was abnormal in 46 (19%) patients. The most frequent abnormalities were isolated +9 (n=11; 24% of abnormal karyotype and considered favorable), isolated del(20q) (n=8; 17% of abnormal karyotype and considered favorable), isolated loss of Y chromosome (n=7; 15% of abnormal karyotype and considered favorable) and isolated +8 (n=5; 11% of abnormal karyotype and considered unfavorable). A total of 9 (20% of abnormal karyotype) patients displayed unfavorable karyotype that included +8 in 7 patients, del(11q) in one patient and +20 in one patient. After a median follow-up of 83 months, 70 (29%) deaths, 48 (20%) thrombotic events, 20 (8%) fibrotic progressions and 7 (3%) leukemic transformations were documented. Comparison of patients with and without cytogenetic abnormalities Patients with abnormal cytogenetics were older (p=0.048), displayed lower platelet count (p=0.005) and were more likely to be high risk (p=0.02); there was no significant correlation with TET2 or ASXL1 mutation. In univariate analysis, patients with abnormal cytogenetics displayed inferior leukemia-free (p=0.007; HR 10.6, 95% CI 1.9-58.7), myelofibrosis-free (p<0.0001; HR 7.7, 95% CI 3.1-19.3) and overall (p=0.13; HR 1.6, 95% CI 0.9-2.8) survival. Furthermore, the difference in overall survival became significant when cytogenetic abnormalities were classified into unfavorable (p=0.006) and favorable (p=0.6) categories. On the other hand, inferior leukemia-free and myelofibrosis-free survival was noted in both patients with favorable and unfavorable cytogenetic abnormalities, when compared to normal karyotype. During multivariable analysis that included age and leukocytosis (≥15 x 10 (9)/L) as covariates, the adverse effect of abnormal cytogenetics on leukemia-free (p=0.009) or myelofibrosis-free (p<0.0001) survival and that of unfavorable karyotype on overall (p=0.05) survival were shown to be independent. Finally, patients with abnormal cytogenetics were less likely to experience thrombosis after diagnosis (p=0.04; HR 0.3, 95% CI 0.09-0.97), an effect that was independent of both age and thrombosis history. Conclusions Cytogenetic abnormalities in PV confer an independent adverse prognostic effect on overall, leukemia-free and myelofibrosis-free survival, but not thrombosis-free survival; the adverse effect on leukemia-free and myelofibrosis-free survival was seen with both favorable and unfavorable cytogenetic abnormalities. Disclosures No relevant conflicts of interest to declare.
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Pollyea, Daniel A., Andrew S. Artz, Wendy Stock, Christopher Daugherty, Lucy Godley, Olatoyosi M. Odenike, Elizabeth Rich, et al. "New Cytogenetic Abnormalities Are Frequent in AML and MDS Relapsing after Allogeneic Hematopoietic Cell Transplantation (HCT)." Blood 108, no. 11 (November 16, 2006): 3675. http://dx.doi.org/10.1182/blood.v108.11.3675.3675.
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Abstract There are limited data regarding the incidence or prognostic value of cytogenetic abnormalities in pts with leukemic relapse after allogeneic hematopoietic cell transplantation (HCT). Between 2002 and 2005, 70 consecutive pts with high risk AML or MDS were transplanted with a reduced intensity preparative regimen of fludarabine 30 mg/m2/day IV (150 mg/m2 total), alemtuzumab SC 20 mg/day IV (100 mg total) D-7 to D-3, and melphalan 140 mg/m2 IV D-2, with tacrolimus given for post-transplantation immunosuppression. Twenty-five pts relapsed or progressed; 21 had AML, 3 had MDS and 1 had mast cell leukemia. Twenty-two pts had cytogenetic analysis available prior to HCT and at relapse. Cytogenetic abnormalities were present in 12/22 (55%) pts prior to HCT. The median OS was 184 days (95% CI: 81 – 300) after relapse. Four pts with cytogenetic abnormalities prior to HCT reverted to a normal karyotype at relapse. Ten pts had no changes in their cytogenetics from HCT to relapse; they either remained normal or retained the same abnormality. Eight pts developed a new clonal abnormality at relapse, and had a median OS of 106 days (95% CI: 30 – 322). There was a non-significant trend toward inferior OS among pts with new abnormalities compared to the other groups (HR = 1.74, 95% CI 0.69 – 4.44, P = 0.24). The higher than previously reported rate of clonal evolution (8/22, 36%) may be due to the high prevalence of refractory disease at HCT in this cohort, more refined cytogenetic analysis, or regimen related factors (e.g. reduced intensity conditioning). The same clonal abnormality with or without new changes occurred in 7/22 pts. Thus, minimal residual disease monitoring in the subset of pts harboring pre-HCT karyotypic derangements may be a viable strategy for early detection and intervention. Our data suggest that clonal evolution at relapse of AML and MDS after HCT is relatively frequent, and in this small series, a trend toward worse outcomes exists for pts who develop new cytogenetic abnormalities. Larger studies are warranted to more completely characterize the prognostic value of cytogenetics and karyotypic evolution at relapse after HCT. Cytogenetic abnormalities for AML/MDS relapsing after HCT (N = 22) Pre HCT* Relapse *History of cytogenetic abnormality any time before HCT **Clonal evolution in 8/22 (36%) No 10 (45%) No 7 (32%) Yes (New)** 3 (14%) Yes 12 (55%) No 4 (18%) Yes (Same) 3 (14%) Yes (New)** 5 (27%)
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Brunner, Andrew Mark, Lillian Werner, Jennifer Lombardi Story, Gabriela Hobbs, Philip C. Amrein, Robert P. Hasserjian, Donna S. Neuberg, and Amir Tahmasb Fathi. "Cytogenetic evolution between diagnosis and relapse and impact on acute myeloid leukemia (AML) reinduction outcomes." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): e18509-e18509. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.e18509.
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e18509 Background: Changes in the subclonal composition of AML may occur after diagnosis and be a mechanism of relapse. Cytogenetic changes between diagnosis and relapse may reveal evolution in clonal composition. We sought to determine whether evolution of patient cytogenetics impacts the response to salvage chemotherapy among AML patients who relapse after first remission. Methods: We identified adults with relapsed AML between 2001-2015. Studied patients received induction at diagnosis, achieved remission, relapsed, and received intensive salvage. APL and primary refractory AML were excluded. We identified cytogenetic abnormalities at relapse, and any clonal changes from diagnosis (gain/loss/no change). Associations with CR2 were analyzed by Fisher’s exact test. OS was from salvage therapy to death or censored at last known alive, with Kaplan Meier estimates. Results: 69 patients (median 54 yo, 58% male) received salvage therapy for relapsed AML. Most (81%) had de novoAML. Patients had favorable (7%), intermediate (70%), and adverse risk (23%) cytogenetics at diagnosis; 51% were normal karyotype. 94% received 7+3-based induction. 42% underwent allo-HCT in CR1. Salvage included 7+3 (n = 22), MEC (n = 36), HiDAC (n = 4), or other regimens (n = 7). Median time from CR1 to relapse was 10 mo (IQR 5, 18). At relapse, 29 patients (42%) gained cytogenetic abnormalities, 8 (12%) lost abnormalities, and 31 (45%) were unchanged. The most common acquired abnormalities involved chromosomes 7, 11, or 17 (each n = 6). 55% achieved CR2/CRi2 (CR2 w/ chromosome gain 48%, loss 38%, no change 65%). Longer CR1 duration was associated with greater likelihood of achieving CR2/CRi2 (p = 0.003). Accounting for CR1 duration, cytogenetic evolution from diagnosis to relapse was not significantly associated with CR2. Improved OS was seen with non-adverse diagnosis cytogenetics (p = 0.0003), longer CR1 (p = 0.035), and transplant in CR1 (p = 0.04). Conclusions: Although AML evolution frequently occurs between diagnosis and relapse (54% of this cohort had cytogenetic changes at relapse), this did not impact CR2 or overall survival. Rather, duration of CR1, likely a surrogate for depth of remission, significantly impacted outcomes.
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Mohamed, Anwar N., Gail Bentley, Michelle L. Bonnett, Margareta Palutke, and Ayad M. Al-Katib. "Cytogenetic Abnormalities in Histologically Confirmed Multiple Myeloma." Blood 106, no. 11 (November 16, 2005): 5082. http://dx.doi.org/10.1182/blood.v106.11.5082.5082.
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Abstract In multiple myeloma, conventional cytogenetics is limited by low proliferation activity of plasma cells in culture. Despite that, nonrandom chromosomal abnormalities have been reported in one third of cases. Recently, the karyotype has emerged as an important prognostic factor in multiple myeloma. In this study, we identified 104 histologically confirmed multiple myeloma cases with satisfactory cytogenetic evaluation and abnormal karyotype. FISH analysis was used to evaluate certain chromosome abnormalities or to monitor treatment response. Hyperdiploid karyotype was found in 67 cases (64%), hypodiploid in 25 cases (24%), and the remaining 12 cases (12%) had a pseudodiploid karyotype. The most common numerical abnormalities were gains of chromosomes 9, 15, 3 followed by chromosomes 19, 21, 11, 7, and 5. Whole chromosome losses were also frequent involving primarily chromosomes 13, 8, 14, 22, and 16. In the hypodiploid cases, loss of chromosome 13 was more evident, seen in 19/25 (76%) cases. Most cases showed also structural rearrangements leading to del(1p), dup(1q), del(6q), del(9p), del(13q), del(17p), del(8p), 3p/3q abnormalities, and 11p/11q abnormalities. Translocations affecting 14q32/IGH region was the most frequent seen 36 times in 34/104 (33%) cases; t(11;14)(q13;q32) in 13 cases, t(1;14), t(6;14), and t(8;14) in 2 cases each, and the remaining cases had various t(V;14) partners or of an undetermined origin. The 14q32/IGH translocations were less frequent in the hyperdiploid karyotypes than the hypodiploid and pseudodiploid karyotypes (18% vs 60%). Nine cases showed break at 8q24/CMYC site; six of those had Burkitt’s-type translocations. Other non-random translocation was t(1;16) seen in three cases. Coventional cytogenetic remains an important tool in elucidating the complex and diverse genetic anomalies of multiple myeloma. Acccordingly well defined cytogenetic subgroups can be identified. At the present time, FISH and other molecular genetic techniques are important adjuncts, but should not be a substitute for conventional karyotyping. The clinical and hematological correlates of the karyotype in our series is being evaluated.
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Chennamaneni, Rachana, Sadashivudu Gundeti, Meher Lakshmi Konatam, Stalin Bala, Ashok Kumar, and Lakshmi Srinivas. "Impact of cytogenetics on outcomes in pediatric acute lymphoblastic leukemia." South Asian Journal of Cancer 07, no. 04 (October 2018): 263–66. http://dx.doi.org/10.4103/sajc.sajc_13_18.
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Abstract Context: In acute lymphoblastic leukemia (ALL), the most important prognostic factors are age, leukocyte count at presentation, immunophenotype, and cytogenetic abnormalities. The cytogenetic abnormalities are associated with distinct immunologic phenotypes of ALL and characteristic outcomes. Aims: The present study was primarily aimed at analyzing the impact of cytogenetics on postinduction responses and event-free survival (EFS) in pediatric patients with ALL. The secondary objective was to study the overall survival (OS). Subjects and Methods: A total of 240 patients with age <18 years and diagnosed with ALL between January 2011 and June 2016 were retrospectively analyzed. Cytogenetics was evaluated with conventional karyotyping or reverse transcriptase polymerase chain reaction. Based on cytogenetic abnormalities, the patients were grouped into five categories, and the outcomes were analyzed. Results: Of the 240 patients, 125 (52%) patients had evaluable cytogenetics. Of these, 77 (61.6%) patients had normal cytogenetics, 19 (15.2%) had t(9;22) translocation, 10 (8%) had unfavorable cytogenetics which included t(9;11), hypodiploidy, and complex karyotype, 10 (8%) had favorable cytogenetics which included t(12;21), t(1;19), and high hyperdiploidy, 9 (7.2%) had miscellaneous cytogenetics. Seventy-one percent of patients were treated with MCP 841 protocol, while 29% of patients received BFM-ALL 95 protocol. The 3-year EFS and OS of the entire group were 52% and 58%, respectively. On univariate analysis, EFS and OS were significantly lower in t(9;22) compared to normal cytogenetics (P = 0.033 and P = 0.0253, respectively) and were not significant for other subgroups compared to normal cytogenetics. On multivariate analysis, EFS was significantly lower for t(9;22) and unfavorable subgroups. Conclusions: Cytogenetics plays an important role in the molecular characterization of ALL defining the prognostic subgroups. Patients with unfavorable cytogenetics and with t(9;22) have poorer outcomes.
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Rangel-Pozzo, Aline, Daiane Corrêa de Souza, Ana Teresa Schmid-Braz, Ana Paula de Azambuja, Thais Ferraz-Aguiar, Tamara Borgonovo, and Sabine Mai. "3D Telomere Structure Analysis to DetectGenomic Instability and Cytogenetic Evolutionin Myelodysplastic Syndromes." Cells 8, no. 4 (April 2, 2019): 304. http://dx.doi.org/10.3390/cells8040304.
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The disease course of myelodysplastic syndromes (MDS) features chromosome instability and clonal evolution, leading to the sequential acquisition of novel cytogenetic aberrations and the accumulation of these abnormalities in the bone marrow. Although clonal cytogenetic abnormalities can be detected by conventional cytogenetics in 50% of patients with MDS, such distinguishing patterns are lacking in the other 50%. Despite the increase in the prognostic value of some biomarkers, none of them is specific and able to discriminate between stable and unstable patients that subsequently progress to acute myeloid leukemia. This pilot study aimed to investigate the potential use of the 3D telomere profiling to detect genomic instability in MDS patients with or without clonal cytogenetic evolution. The comparison between different time points in patients with cytogenetic changes showed that in the CD34+ MDS cells, there was a significant decrease in the total number of telomeric signals, the average intensity of signals and the total intensity of telomeres. By contrast, the number of aggregates increased during cytogenetic evolution (p < 0.001). This pattern was observed only for MDS patients with cytogenetic evolution but was absent in patients without cytogenetic changes. In conclusion, we demonstrated that the 3D nuclear telomere organization was significantly altered during the MDS disease course, and may have contributed to cytogenetic clonal evolution.
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Nashelsky, Marcus B., Michelle M. Hess, Dennis D. Weisenburger, Jene L. Pierson, Martin A. Bast, James O. Armitage, and Warren G. Sanger. "Cytogenetic Abnormalities in B-Immunoblastic Lymphoma." Leukemia & Lymphoma 14, no. 5-6 (January 1994): 415–20. http://dx.doi.org/10.3109/10428199409049698.
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Schanz, Julie, Friederike Braulke, and Detlef Haase. "RARE CYTOGENETIC ABNORMALITIES IN MYELODYSPLASTIC SYNDROMES." Mediterranean Journal of Hematology and Infectious Diseases 7 (April 23, 2015): e2015034. http://dx.doi.org/10.4084/mjhid.2015.034.
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The karyotype represents one of the main cornerstones for the International Prognostic Scoring System (IPSS) and the revised IPSS-R (IPSS-R) that are most widely used for prognostication in patients with myelodysplastic syndromes (MDS). The most frequent cytogenetic abnormalities in MDS, i.e. del(5q), -7/del(7q), +8, complex karyotypes, or –Y have been extensively explored for their prognostic impact. The IPSS-R considers also some less frequent abnormalities such as del(11q), isochromosome 17, +19, or 3q abnormalities. However, more than 600 different cytogenetic categories had been identified in a previous MDS study. This review aims to focus interest on selected rare cytogenetic abnormalities in patients with MDS. Examples are numerical gains of the chromosomes 11 (indicating rapid progression), of chromosome 14 or 14q (prognostically intermediate to favorable), -X (in females, with an intermediate prognosis), or numerical abnormalities of chromosome 21. Structural abnormalities are also considered, e.g. del(13q) that is associated with bone marrow failure syndromes and favorable response to immunosuppressive therapy. These and other rare cytogenetic abnormalities should be integrated into existing prognostication systems such as the IPSS-R. However, due to the very low number of cases, this is clearly dependent on international collaboration. Hopefully, this article will help to inaugurate this process.
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Becher, Ulrich, Julie Schanz, Friederike Braulke, and Detlef Haase. "RARE CYTOGENETIC ABNORMALITIES IN MYELODYSPLASTIC SYNDROMES." Mediterranean Journal of Hematology and Infectious Diseases 7, no. 1 (April 23, 2015): 2015. http://dx.doi.org/10.4084/mjhid.2015.34.
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Liou, Jui-Der, Chih-Ping Chen, W. Roy Breg, John C. Hobbins, Maurice J. Mahoney, and Teresa L. Yang-Feng. "Fetal blood sampling and cytogenetic abnormalities." Prenatal Diagnosis 13, no. 1 (January 1993): 1–8. http://dx.doi.org/10.1002/pd.1970130102.
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Stuart, A. Graham, Andrew D. J. Pearson, John Emslie, Anne Lennard, E. Valerie Davison, Robert H. Perry, and Peter J. Crawford. "Cytogenetic abnormalities in a disseminated medulloblastoma." Medical and Pediatric Oncology 21, no. 4 (1993): 295–98. http://dx.doi.org/10.1002/mpo.2950210412.
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Bendavid, Claude, Valérie Dupé, Lucie Rochard, Isabelle Gicquel, Christèle Dubourg, and Véronique David. "Holoprosencephaly: An update on cytogenetic abnormalities." American Journal of Medical Genetics Part C: Seminars in Medical Genetics 154C, no. 1 (February 15, 2010): 86–92. http://dx.doi.org/10.1002/ajmg.c.30250.
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Ladanyi, Marc, Nasser Z. Parsa, Kenneth Offit, Mitchell S. Wachtel, Daniel A. Filippa, and Suresh C. Jhanwar. "Clonal cytogenetic abnormalities in Hodgkin's disease." Genes, Chromosomes and Cancer 3, no. 4 (July 1991): 294–99. http://dx.doi.org/10.1002/gcc.2870030408.
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Dobin, Sheila M., Charles P. Harris, Robert F. Peterson, V. O. Speights, James A. Reynolds, K. Scott Coffield, and Richard C. Klugo. "Cytogenetic abnormalities in renal oncocytic neoplasms." Genes, Chromosomes and Cancer 4, no. 1 (January 1992): 25–31. http://dx.doi.org/10.1002/gcc.2870040104.
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Fenaux, P., D. Lucidarme, J. L. Laï, and F. Bauters. "Favorable cytogenetic abnormalities in secondary leukemia." Cancer 63, no. 12 (June 15, 1989): 2505–8. http://dx.doi.org/10.1002/1097-0142(19890615)63:12<2505::aid-cncr2820631224>3.0.co;2-z.
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Betts, DR, KE Leibundgut, A. Feldges, HJ Plüss, and FK Niggli. "Cytogenetic abnormalities in Langerhans cell histiocytosis." British Journal of Cancer 77, no. 4 (February 1998): 552–55. http://dx.doi.org/10.1038/bjc.1998.89.
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Shaffer, Lisa G., Arthur L. Beaudet, Arthur R. Brothman, Betsy Hirsch, Brynn Levy, Christa Lese Martin, James T. Mascarello, and Kathleen W. Rao. "Microarray analysis for constitutional cytogenetic abnormalities." Genetics in Medicine 9, no. 9 (September 2007): 654–62. http://dx.doi.org/10.1097/gim.0b013e31814ce3d9.
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Antonini, P., A. M. Venuat, R. Berger, G. Caillou, J. L. Rossignol, and C. Parmentier. "100 Cytogenetic abnormalities in thyroid tumors." Cancer Genetics and Cytogenetics 38, no. 2 (April 1989): 190. http://dx.doi.org/10.1016/0165-4608(89)90627-4.
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Moertel, Cheryl A., Richard J. Dahl, Paul G. Stalboerger, David W. Kimmel, Bernd W. Scheithauer, and Robert B. Jenkins. "Gliosis specimens contain clonal cytogenetic abnormalities." Cancer Genetics and Cytogenetics 67, no. 1 (May 1993): 21–27. http://dx.doi.org/10.1016/0165-4608(93)90039-o.
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Alvares, C. J., W. B. Swaney, I. Janecka, E. L. Barnes, and S. M. Gollin. "Cytogenetic abnormalities in a recurrent hemangiopericytoma." Cancer Genetics and Cytogenetics 66, no. 2 (April 1993): 160. http://dx.doi.org/10.1016/0165-4608(93)90324-f.
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McCarthy, C. M. T., and S. M. Benson. "Cytogenetic abnormalities in acute myelomonocytic leukaemia." Mutation Research/Environmental Mutagenesis and Related Subjects 164, no. 3 (June 1986): 195–96. http://dx.doi.org/10.1016/0165-1161(86)90021-x.
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Dzitsiuk, V. V., and H. T. Tipilo. "CHROMOSOMAL ABNORMALITIES SHEEP." Animal Breeding and Genetics 53 (April 27, 2017): 209–14. http://dx.doi.org/10.31073/abg.53.28.
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Successful and creative plant-breeding work in a stock-raising is based on the estimation of genetic potential of separate breeds, herds and individuals, that is impossible without thorough genetic- populations knowledge. Knowledge of features of caryotype gives an opportunity objectively to estimate the breeds of animals taking into account their population-cytogenetic features, that assists more complete idea about the evolution of breeds. However such important agricultural object, as a domestic sheep, remains cytogenetic poorly studied, especially in a population-cytogenetic aspect.In literature different breeds have small information about frequency and spectrum of the inherited anomalies and populations of sheep. Most chromosomal and genic anomalies of sheep in general not research, although for practice of plant-breeding work necessary knowledge of reasons of their appearance. Caryotype of sheep is presented by 54 chromosomes, from them 26 pairs of autsom and one pair of sexual chromosomes (ХХ or ХУ). Three pairs of large metacentric and 23 pairs of acrocentric chromosomes of different size enter in the complement of autsom. For sheep as well as for other animals characteristic chromosomal polymorphism as a numerical varying of chromosomes in caryotype (aneuploidi and poliploidi), morphological aberations and associations of separate chromosomes. Chromosomal anomalies of sheep are reason of forming of nonviable gamet, that results in death of embryos on the early stages, and, as a result, to the considerable economic losses in economies. The facts of chromosomal aberation educed for sheep testify to the necessity of cytogenetic control of tribal animals, especially rams, with the aim of exposure of animals-transmitters of undesirable changes in caryotype and exception of them from a plant-breeding process.
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Paner, Gladell P., Valerie Lindgren, Kris Jacobson, Kathleen Harrison, Ying Cao, Steve C. Campbell, Robert C. Flanigan, and Maria M. Picken. "High Incidence of Chromosome 1 Abnormalities in a Series of 27 Renal Oncocytomas: Cytogenetic and Fluorescence In Situ Hybridization Studies." Archives of Pathology & Laboratory Medicine 131, no. 1 (January 1, 2007): 81–85. http://dx.doi.org/10.5858/2007-131-81-hiocai.
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Abstract Context.—It has recently been shown by cytogenetics that there is a high incidence of chromosome 1 abnormalities in renal oncocytomas. Objective.—To confirm the cytogenetic results by fluorescence in situ hybridization (FISH) analysis. Design.—Nine additional cytogenetic analyses were added to those reported in our recent study, with a total of 27 tumors studied, which makes it the largest series of renal oncocytomas studied to date by cytogenetics and/or FISH. We used the LSI 1p36/LSI 1q25 Dual Color Probe Set to make the analyses. Results.—In this study, combined cytogenetics and FISH showed loss of chromosome arm 1p1 in 48% of renal oncocytomas. By FISH, deletion of 1p36.3 was observed in 59% of renal oncocytomas, whereas by cytogenetics, abnormality in chromosome 1 was seen in 32% of tumors. However, the incidence of chromosome 1 abnormalities among 9 bilateral tumors was much higher than in single tumors (88% vs 28%, respectively). Loss of only the 1p36.3 site occurred in 2 renal oncocytomas with translocation of chromosome 1, as shown by cytogenetics. Concordance between the 2 techniques, when they were used simultaneously to detect chromosome 1p1 abnormality, was 82%. Conclusions.—This study further confirmed our prior results demonstrating the widespread occurrence of chromosome 1 abnormalities in renal oncocytomas. Although no abnormalities in chromosome 1 in tumors with normal karyotypes were detected by FISH using the current set of probes, a much higher incidence of such abnormalities was found in bilateral tumors, suggesting that genetic alterations related to the development of renal oncocytoma reside in this region.
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Short, Nicholas J., Hagop M. Kantarjian, Elias Jabbour, Susan O'Brien, Stefan Faderl, Jan A. Burger, Rebecca Garris, et al. "Persistence of Cytogenetic Abnormalities at Complete Remission Is Not Prognostic for Relapse-Free or Overall Survival in Adult Patients with Acute Lymphoblastic Leukemia." Blood 126, no. 23 (December 3, 2015): 1416. http://dx.doi.org/10.1182/blood.v126.23.1416.1416.
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Abstract Background: Cytogenetic abnormalities are identified at the time of diagnosis in approximately 80% of patients with acute lymphoblastic leukemia (ALL). In acute myelogenous leukemia (AML), the detection of persistent abnormal cytogenetics at complete remission (ACCR) is associated with shorter relapse-free survival (RFS) and overall survival (OS) compared to patients with normal cytogenetics at CR (NCCR). However, the incidence and prognostic significance of ACCR in adult patients with ALL is unknown. Methods: We evaluated 324 adult patients with ALL and abnormal cytogenetics at baseline who were treated on frontline induction chemotherapy protocols between 6/2001 and 3/2015 and achieved complete remission (CR) or CR without platelet recovery (CRp). Bone marrow specimens for cytogenetic and minimal residual disease (MRD) assessment were obtained at the time of CR. Cytogenetic abnormalities were classified according to standard conventions (Moorman et al., Blood 2007;109:3189-97). MRD by multi-parameter flow cytometry (MFC) was assessed with a sensitivity of 0.01% using a 15-marker, 4-color panel in the first half of the study period; subsequently a 6-color panel was used. Results: 272 patients (84%) had cytogenetic analysis performed at the time of remission and were evaluable for this analysis. Median age was 48 years (range, 16-84) and median WBC at presentation was 11.6 x109/L (range, 0.4-629.4 x109/L). A hyperCVAD backbone was used for induction in 237 patients (87%) and augmented BFM was used in 35 (13%). All patients with Philadelphia positive (Ph+) ALL were treated with a tyrosine kinase inhibitor added to the chemotherapy regimen. 245 patients (90%) had pre-B ALL, 14 (5%) had pre-T ALL and 13 (5%) had Burkitt or Burkitt-like leukemia. Cytogenetics at baseline were Ph+ in 119 (44%), hyperdiploid in 31 (11%), complex in 18 (7%), MLL rearranged in 16 (6%), hypodiploid in 9 (3%) and miscellaneous in 79 (29%). Median time to CR was 23 days (range 14 to 84 days). Among the 272 patients, ACCR was observed in 26 (9.6%). Baseline characteristics associated with ACCR were Ph+ ALL (62% of ACCR group vs. 42% of NCCR group, P=0.055) and longer mean time to CR (29.8 ± 15.6 days for ACCR group vs. 26.0 ± 9.7 days for NCCR group, P=0.07). Median RFS was 22.4 months (range, 12.3 months to not reached) for patients with ACCR vs. 47.7 months (range, 29.5 to 125 months) in those patients with NCCR (P=0.31). Median OS did not differ between the ACCR (98.7 months [range, 17.1 months to not reached]) and NCCR groups (67.3 months [range, 46.6 months to not reached], P=0.86). There was also not a significant difference in RFS or OS between the ACCR and NCCR groups when only Ph+ patients were evaluated. Among the 227 patients evaluable for MRD by MFC, MRD positivity at CR was observed in 78 patients (34%) and was highly associated with shorter RFS and OS (P<0.01 for both). The specificity of ACCR for detecting MRD (as assessed by MFC) was 43%, and there was overall poor correlation between these two methods for the detection of residual disease (P=0.47). When patients were stratified by MRD status as assessed by MFC, the presence of absence of persistent cytogenetic abnormalities did not add additional prognostic information (Fig. 1 and 2). Conclusions: There is poor association between MRD assessment by MFC and the presence or absence of cytogenetic abnormalities at CR in adult patients with ALL. Although ACCR has prognostic significance in AML, ACCR is not associated with adverse outcomes in ALL and therefore should not be used to guide prognostication or therapeutic decisions. Figure 1. Relapse-free survival of patients with and without cytogenetic abnormalities at CR, stratified by MRD status Figure 1. Relapse-free survival of patients with and without cytogenetic abnormalities at CR, stratified by MRD status Figure 2. Overall survival of patients with and without cytogenetic abnormalities at CR, stratified by MRD status Figure 2. Overall survival of patients with and without cytogenetic abnormalities at CR, stratified by MRD status Disclosures Faderl: Celgene Corp.: Other: Advisory Board. Burger:Pharmacyclics LLC, an AbbVie Company: Research Funding. Konopleva:Novartis: Research Funding; AbbVie: Research Funding; Stemline: Research Funding; Calithera: Research Funding; Threshold: Research Funding. Cortes:Pfizer: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Teva: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; ARIAD Pharmaceuticals Inc.: Consultancy, Research Funding.