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1.
Indian J Med Res ; 153(4): 475-483, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34380794

RESUMO

Background & objectives: B-cell chronic lymphocytic leukaemia (B-CLL) is one of the most common forms of adult leukaemia, with a highly variable clinical course. Specific chromosomal and genetic aberrations are used clinically to predict prognosis, independent from conventional clinical markers. Molecular cytogenetic methods such as fluorescence in situ hybridization (FISH) detect aberrations in up to 80 per cent B-CLL patients. This study was conducted to score the frequencies of recurrent aberrations, i.e., del(13q14), trisomy 12, del(11q22), del(17p13), del(6q21) and IgH (immunoglobulin heavy chain) translocations and to understand their role in prognostication and risk stratification. Methods: FISH studies were performed on bone marrow aspirate or peripheral blood of 280 patients using commercially available disease-specific probe set. The data were correlated with clinical and haematological parameters such as low haemoglobin, splenomegaly and lymphadenopathy. Results: Chromosomal aberrations were detected in 79 per cent of patients, with del(13q14) (57%) as the most common cytogenetic aberration, followed by trisomy 12 (27%), del(11q22) (22%), t(14q32) (19%), del(17p13) (18%) and del(6q21) (9%). Single or in coexistence with other aberration del(13q14) had a favourable outcome in comparison to del(11q22), t(14q32), del(17p13) and del(6q21) which were associated with advanced stages of the disease. Trisomy 12 had a variable clinical course. Interpretation & conclusions: FISH was found to be a sensitive and efficient technique in detecting the prevalence of recurrent cytogenetic abnormalities. Each of these aberrations is an important independent predictor of disease progression and survival which aids in designing risk-adapted treatment strategies for better disease management.


Assuntos
Leucemia Linfocítica Crônica de Células B , Aberrações Cromossômicas , Análise Citogenética , Humanos , Hibridização in Situ Fluorescente , Leucemia Linfocítica Crônica de Células B/diagnóstico , Leucemia Linfocítica Crônica de Células B/genética , Prognóstico
2.
Cancer Genet ; 256-257: 17-20, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33823403

RESUMO

Acute Myeloid Leukemia (AML) is a heterogeneous disease with respect to morphology, immunophenotype, chromosomal abnormalities and genetic lesions. While a majority of AML cases harbour recurrent chromosomal abnormalities, several rare, apparently unique or novel aberrations may be identified by conventional cytogenetics. In fact, with the prognostic relevance of chromosomal abnormalities, and with the advent of new-age, target-specific therapy, identifying such aberrations becomes vital. In this study, we present a case of pediatric AML with ins(19;X)(q13.1;p11.2q28) and t(1;11)(q10;p10), both, novel, previously unreported chromosomal abnormalities in AML. Post induction, both these clonal cytogenetic abnormalities persisted. The documentation of this case will help determine the significance of these cytogenetic abnormalities. Also, this case exemplifies the importance of cytogenetics in the complete characterization and risk stratification of AML patients.


Assuntos
Inversão Cromossômica , Análise Citogenética , Translocação Genética , Criança , Feminino , Seguimentos , Humanos , Cariótipo
3.
Cancer Genet ; 254-255: 65-69, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33647813

RESUMO

Intrachromosomal amplification of RUNX1 gene on chromosome 21 (iAMP21) is a rare occurrence in acute myeloid leukemia (AML). Herein, we describe a case of AML with amplification of RUNX1 and its insertion on chromosome 2 detected by conventional karyotyping and confirmed by metaphase FISH. A six-year-old female was diagnosed as acute myeloid leukemia with monocytic differentiation. The patient's bone marrow revealed 74% blasts which were MPO negative. Conventional karyotyping revealed a complex karyotype, with rearrangements in chromosomes 1, 2, 7, 8 and hsr(21). FISH on interphase cells with LSI RUNX1-RUNX1T1 dual colour dual fusion translocation probe showed 6-7 copies of RUNX1 signal. Metaphase FISH with LSI RUNX1-RUNX1T1 probe confirmed amplification of RUNX1 and insertion of amplified RUNX1 sequences on long arm of chromosome 2. Induction chemotherapy was initiated, however, the patient died within one month of diagnosis suggesting poor outcome associated with this novel finding. Insertion of amplified RUNX1 on another chromosome has not yet been reported so far.


Assuntos
Cromossomos Humanos Par 2/genética , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Amplificação de Genes , Leucemia Mieloide Aguda/genética , Mutagênese Insercional/genética , Medula Óssea/patologia , Criança , Evolução Fatal , Feminino , Humanos , Interfase , Cariótipo
4.
Blood Adv ; 5(5): 1178-1193, 2021 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-33635331

RESUMO

The use of pediatrics-inspired protocols in adolescent and young adult (AYA) acute lymphoblastic leukemia (ALL) results in superior survival compared with the adult protocols. Pediatrics-inspired protocols carry an increased risk of toxicity and treatment-related mortality in low resource settings, which can offset the potential benefits. We studied the outcomes and prognostic factors in the treatment of AYA ALL with a pediatrics-inspired regimen. We retrieved data regarding demographics, investigations, treatment details, and toxicities from the electronic medical records of patients diagnosed with ALL in the 15- to 25-year-old age group who were initiated on a modified Berlin-Frankfurt-Münster 90 (BFM-90) protocol between January 2013 and December 2016 at the Tata Memorial Centre. A total of 349 patients in the 15- to 25-year-old age group were treated with a modified BFM-90 protocol. The use of this pediatrics-inspired protocol resulted in a 3-year event-free survival (EFS) and overall survival (OS) of 59.4% and 61.8%, respectively. Only 15 patients underwent an allogeneic stem cell transplant. Minimal residual disease (MRD) persistence postinduction emerged as the only factor predictive of poor outcomes. A modified BFM-90 protocol is an effective and safe regimen for AYA ALL with an OS and EFS comparable to the published literature.


Assuntos
Citarabina , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adolescente , Adulto , Criança , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Prognóstico , Transplante de Células-Tronco , Adulto Jovem
5.
Artigo em Inglês | MEDLINE | ID: mdl-33629824

RESUMO

BACKGROUND AND AIM: Molecular mechanism of translocation and outcome in variant chronic myeloid leukaemia (vCML) has been a topic of debate. While several cytogenetic studies suggest a low response to Imatinib Mesylate, others demonstrate a similar disease course in both classical and vCML. Besides, many studies comprehensively also link tyrosine kinase domain (TKD) mutations with aggressive clinical outcome. Thus, we aim to study the molecular mechanism of translocation, identify the third partner chromosomes and comment on the disease course and clinical outcome. METHOD: We cytogenetically characterised 25 vCML cases to determine the third partner chromosome, mechanism of translocation and prognostic outcome. We also compared vCML cases with and without TKD mutation to most appropriately outline the clinical consequence and ascertain the potent cause of unresponsiveness to treatment. RESULTS: Third partner chromosome in variant translocation was defined by conventional and molecular cytogenetics. Although in our study most cases showed inadequate clinical response attributable to TKD mutation rather than variant translocation, we observed an inferior outcome in cases involving chromosome 5 as the third partner. CONCLUSION: Thus, we conclude that characterising and reporting new cases of variant translocations, involving various different chromosomes as third partner (with different breakpoints) by cytogenetics, will lead to a better understanding of the disease. To the best of our knowledge, this kind of delineate study has not been applied to precisely comment on the prospects of cytogenetically characterised vCML.

8.
Blood Cells Mol Dis ; 85: 102465, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32693366

RESUMO

Ploidy, besides known translocations in lymphoblasts, is a strong predictor of prognosis in B- cell progenitor acute lymphoblastic leukemia (BCP-ALL). While hyperdiploidy with >50 chromosomes shows a favourable outcome, hypodiploidy with <45 chromosomes have a dismal clinical outcome. However, there exists a small subset where both the hypodiploid and hyperdiploid clones are apparent either by cytogenetics or flow cytometry and are defined partially masked hypodiploids or mosaics based on the percentage of clonal population. These patients are essentially hypodiploids, and show the hyperdiploid clone as a consequence of endoreduplication of the primary hypodiploid clone- A phenomenon of successive replication of genome without mitosis (cytokinesis) resulting in increased ploidy. In the current study, we present the complete clinical, hematological and cytogenetic profile of 11 such newly diagnosed mosaics or partially masked hypodiploid BCP-ALL cases.


Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Adolescente , Adulto , Criança , Pré-Escolar , Análise Citogenética , Endorreduplicação , Feminino , Humanos , Masculino , Ploidias , Leucemia-Linfoma Linfoblástico de Células Precursoras B/diagnóstico , Prognóstico , Translocação Genética , Adulto Jovem
9.
Cancer Genet ; 228-229: 17-20, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30553467

RESUMO

Hepatosplenic T-cell lymphoma (HSTL) is a rare subtype of peripheral T-cell lymphoma predominantly seen in young males. This disease presents with isolated hepatosplenomegaly and thrombocytopenia with sinusoidal infiltration of liver and sinusal infiltration of spleen. Immunophenotype shows positivity for CD3, CD7, TCRγδ or TCRαß, CD38 and double negative for CD4, CD8, TdT, CD5, and CD56. Isochromosome 7q with or without trisomy 8 is seen in HSTL. Recently, ring chromosome 7 has also been identified as a new abnormality. We describe the clinical, immunophenotypic and cytogenetic analysis in a 24-year-old woman. We present an unusual case of TCRγδ positive T-cell lymphoma with aberrant expression of CD19, which is a B-cell lymphoid marker, with amplification of 7q region and subsequent formation of ring chromosome 7 and trisomy 8. This is the second case of HSTL, positive for CD19 and first case presenting with ring chromosome 7 and trisomy 8 in a CD19 positive HSTL which is a rare finding in T-cell lymphoma and needs to be explored further.


Assuntos
Antígenos CD19/imunologia , Cromossomos Humanos Par 7 , Cromossomos Humanos Par 8 , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Linfoma de Células T/diagnóstico , Linfoma de Células T/genética , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Cromossomos em Anel , Neoplasias Esplênicas/diagnóstico , Neoplasias Esplênicas/genética , Trissomia , Evolução Fatal , Feminino , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Neoplasias Hepáticas/imunologia , Linfoma de Células T/imunologia , Neoplasias Esplênicas/imunologia , Adulto Jovem
10.
Indian J Cancer ; 55(1): 9-15, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30147087

RESUMO

Introduction: There is paucity of data from India about the outcomes of patients with various hematological malignancies. Since its formation in 2009, the adult hematolymphoid disease management group of the Tata Memorial Centre is dedicated to the treatment of hematological malignancies alone. In this report, we present the outcomes of patients treated at our centre over a 5 year period for various haematological malignancies in both transplant and non-transplant setting. Methods: This is a retrospective analysis of all patients registered in adult hematolymphoid disease management group between 1st January 2010 to 31st December 2014. Patients not treated at our centre were excluded from survival analysis. The cut off date for survival analysis was 31st January 2016. Results: Overall, 1869, 3633 and 544 patients with acute leukemias, various lymphomas and myeloma respectively were registered at our centre from 1st January 2010 to 31st December 2014. Of these, 1178 (63%), 3091 (85%) and 454 (83%) respectively received treatment at our centre. The cumulative probability of 5 year overall survival for patients with acute leukemias, Hodgkin's lymphoma, non-Hodgkin lymphoma and myeloma treated at our centre is 40%, 85%, 78% and 40% respectively. Four hundred and fifteen stem cell transplants were done between 14th November 2007 to 31st December 2014 with 46% being allogeneic and 54% being autologous. The 5 year overall survival of patients with allogenic and autologous transplant was 52% and 63% respectively. Conclusions: This is the largest single centre data on outcomes of various haematological malignancies from India. This real world data identifies areas which need further attention to improve outcomes.


Assuntos
Neoplasias Hematológicas/terapia , Transplante de Células-Tronco , Transplante Autólogo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Neoplasias Hematológicas/epidemiologia , Neoplasias Hematológicas/patologia , Doença de Hodgkin/epidemiologia , Doença de Hodgkin/patologia , Doença de Hodgkin/terapia , Humanos , Índia/epidemiologia , Linfoma não Hodgkin/epidemiologia , Linfoma não Hodgkin/patologia , Linfoma não Hodgkin/terapia , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/epidemiologia , Mieloma Múltiplo/patologia , Mieloma Múltiplo/terapia , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
11.
Indian J Med Res ; 144(4): 536-543, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28256461

RESUMO

BACKGROUND & OBJECTIVES: Multiple myeloma (MM) is a plasma cell malignancy characterized by cytogenetic heterogeneity. In comparison with conventional karyotyping, fluorescence in situ hybridization (FISH) can efficiently detect various genetic changes in non-cycling plasma cells in 50-90 per cent of MM cases. The present study was undertaken in MM patients to evaluate the frequency and clinico-pathological significance of various cytogenetic abnormalities in the Indian population. METHODS: Interphase FISH was applied on purified plasma cells of 475 patients with MM using specific probes. Interphase FISH for 1q gain/1q amplification was performed on a separate group of 250 newly diagnosed MM patients. RESULTS: Low frequency of Δ13 [-13/del(13q)] (32%) and t(11;14) (5%) was observed in our 475 patients probably due to ethnic diversity. Clustering of Δ13, del(17)(p13.1) and IgH translocations in non-hyperdiploidy confirmed prognostic significance of ploidy in MM. t(4;14) and del(17)(p13.1) were high-risk groups due to correlation with high serum ß2-microglobulin, increased plasma cells and advanced disease. Hyperdiploidy and t(14;16) were associated with higher age group. In a separate group of 250 patients, 1q amplification [amp(1q)] in combination with Δ13 and/or del(17p) with t(4;14) revealed association with adverse clinico-laboratory features, which confirmed progressive role of amp(1q) with adverse prognostic impact. Amp(1q) was clustered at 1q21 and 1q25 loci. INTERPRETATION & CONCLUSIONS: Based on our findings, it appears that comprehensive analysis of various cytogenetic aberrations by interphase FISH is a powerful strategy being adapted for risk stratification of MM.


Assuntos
Citodiagnóstico , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/genética , Prognóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Aneuploidia , Aberrações Cromossômicas , Deleção Cromossômica , Análise Citogenética , Feminino , Humanos , Hibridização in Situ Fluorescente , Índia , Cariotipagem , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/patologia , Translocação Genética
12.
Indian J Hum Genet ; 13(3): 114-8, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21957359

RESUMO

We report a case of AML-M1 with 5q aberration at diagnosis. The patient was treated with high-dose chemotherapy (HDCT). After remission induction, he received allogenic peripheral blood stem cell transplantation (PBSCT) from an HLA-match donor brother. The successive follow-up conventional cytogenetics investigations in remission after HDCT and PBSCT revealed cytogenetic remission. The most interesting observation in this case is that relapsed marrow revealed the emergence of an entirely new, highly aberrant, unrelated clone with unusual translocations t(6;17)(p23;p11.2),+8,der(8)dup inv(8)(q23qter), t(10;19)(q26;q13.3) 4½ months after PBSCT. Our findings suggest the possibility of a mutagenic effect of HDCT and myeloablative intense chemotherapy before PBSCT that could have induced a genetic lesion in the recipient's genetically unstable stem cells in an environment of immunosuppression. The highly complex nature of the clone and the rapid clonal evolution indicates the possibility of selective pressure with proliferative advantage.

13.
Leuk Res ; 29(5): 517-26, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-15755504

RESUMO

Studies were done to investigate MLL gene aberrations using Conventional Cytogenetics, Southern blotting as well as FISH using a panel of probes on 218 cases which included 206 cases of pediatric/young adult ALL and 12 cases of infantile acute leukemias from Tata Memorial Hospital, India. The incidence of MLL gene rearrangements in acute lymphoblastic leukemia (ALL) was 9.4% which included infants as well as pediatric/young adults. In infantile group which included ALL as well as AML cases, MLL gene rearrangement was very common (75% frequency). Application of metaphase-FISH helped unravel MLL rearrangements not only as a result of translocations but also inversions, insertions, partial deletion, duplications, partial duplication-->self-fusion. Besides age, MLL gene rearrangements showed significant association with hyperleukocytosis, peripheral blood blast percentage and early Pre-B phenotype. Clinical outcome of patients with MLL gene rearrangements revealed unfavorable prognosis.


Assuntos
Aberrações Cromossômicas , Proteínas de Ligação a DNA/genética , Rearranjo Gênico , Leucemia Mieloide Aguda/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Proto-Oncogenes/genética , Fatores de Transcrição/genética , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Histona-Lisina N-Metiltransferase , Humanos , Hibridização in Situ Fluorescente , Índia , Lactente , Cariotipagem , Masculino , Mutação , Proteína de Leucina Linfoide-Mieloide , Prognóstico
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