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1.
J Cell Commun Signal ; 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34596797

RESUMO

Chronic myeloid leukemia (CML) epitomises successful targeted therapy, where inhibition of tyrosine kinase activity of oncoprotein Bcr-Abl1 by imatinib, induces remission in 86% patients in initial chronic phase (CP). However, in acute phase of blast crisis, 80% patients show resistance, 40% among them despite inhibition of Bcr-Abl1 activity. This implies activation of either Bcr-Abl1- independent signalling pathways or restoration of signalling downstream of inactive Bcr-Abl1. In the present study, mass spectrometry and subsequent in silico pathway analysis of differentiators in resistant CML-CP cells identified key differentiators, 14-3-3ε and p38 MAPK, which belong to Bcr-Abl1 pathway. Their levels and activity respectively, indicated active Bcr-Abl1 pathway in CML-BC resistant cells, though Bcr-Abl1 is inhibited by imatinib. Further, contribution of these components to resistance was demonstrated by inhibition of Bcr-Abl1 down-stream signalling by knocking-out of 14-3-3ε and inhibition of p38 MAPK activity. The observations merit clinical validation to explore their translational potential.

2.
Blood Adv ; 5(17): 3436-3444, 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34461632

RESUMO

The expression of CD20 in precursor B-cell acute lymphoblastic leukemia (B-ALL) is associated with poor outcomes. The addition of rituximab to intensive chemotherapy in CD20+ ALL has led to improved outcomes in several studies. However, there is no clear evidence regarding the optimal number of doses and its benefit without an allogeneic stem cell transplant. Achieving measurable residual disease (MRD)-negative status postinduction would reduce the requirement for a transplant. Novel approaches are needed to induce a higher proportion of MRD-negative complete remission in patients with high-risk ALL. Given bortezomib's activity in relapsed ALL and its synergism with rituximab in B-cell lymphomas, the addition of bortezomib to rituximab and chemotherapy may provide an incremental benefit in CD20+ precursor B-ALL. We conducted a phase 2 study to test the activity of bortezomib and rituximab in combination with a pediatric-inspired regimen during induction therapy in newly diagnosed adolescents and adults (aged >14 years) with CD20+, Philadelphia-negative precursor B-ALL; bone marrow MRD negativity at the end of induction was the primary end point. From December 2017 through August 2019, a total of 35 patients were enrolled. End-of-induction MRD-negative status was achieved in 70.9% of patients, as opposed to 51.7% in the historical cohort treated with chemotherapy alone. MRD-negative rates improved to 87.5% post-consolidation. At a median follow-up of 21 months, event-free survival and overall survival rates were 78.8% (95% confidence interval, 66-94) and 78.7% (95% confidence interval, 65.8-94), respectively. There was no significant increase in toxicity with bortezomib and rituximab compared with the historical cohort. The incidence of neuropathy was 26% (all less than grade 3). The combination of bortezomib, rituximab, and a pediatric-inspired ALL regimen was active and well tolerated in de novo CD20+ Philadelphia-negative precursor B-ALL. This trial was registered with the Clinical Trials Registry-India as CTRI/2017/04/008393(http://ctri.nic.in/Clinicaltrials).

3.
Int J Lab Hematol ; 2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34387930

RESUMO

INTRODUCTION: Juvenile myelomonocytic leukemia (JMML) is a rare childhood neoplasm (<5% cases), which has been categorized under myelodysplastic/myeloproliferative neoplasms (MDS/MPN) in the recent classification by the World Health Organization. METHODS: We developed a 51-gene (151.5kB) low-cost targeted myeloid panel based on single-molecule molecular inversion probes to comprehensively evaluate the genomic profile of Juvenile myelomonocytic leukemia (JMML). RESULTS: A total of 50 children with clinical and pathological features of JMML were sequenced at high coverage. Among the 50 patients, 44(88%) harbored mutations in one of the RAS/MAPK-pathway genes, most frequently in NRAS (32%), followed by PTPN11 (28%) and NF1 (22%). One-fifth of children had more than one mutation, with 5 cases harboring two RAS pathway mutations. Monosomy 7 was detected in 32% (16) patients, and five of these did not harbor any RAS pathway mutations. Children with monosomy 7 showed shorter overall survival compared with their wild-type counterparts (P = .02). CONCLUSION: Our study highlights that comprehensive genomic profiling identifies at least one mutation in almost 90% of JMML patients. Performing genomic analysis at baseline might help in triaging children with JMML for allogenic stem cell transplant in resource-constrained settings.

4.
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
5.
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.

6.
Transpl Infect Dis ; 23(4): e13576, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33523551

RESUMO

Recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT) are an immunocompromised group who are likely to develop severe complications and mortality because of coronavirus disease 2019 (COVID-19). We report here a 61-year-old male patient of primary myelofibrosis who underwent an allo-HSCT 6 years earlier, had chronic graft-versus-host disease (cGVHD) involving the liver, lung, eyes, and skin, (with recurrent episodes of pulmonary infections) who developed severe COVID-19. The patient was treated with tocilizumab, and a combination of lopinavir/ritonavir, ribavirin, interferon-ß1b. He was discharged after 31 days with full recovery. Tocilizumab, a humanized monoclonal antibody against IL6, has been shown to benefit respiratory manifestations in severe COVID19. However, this is first report, to our knowledge, of its use and benefit in a post HSCT recipient.


Assuntos
COVID-19 , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Anticorpos Monoclonais Humanizados , Antivirais/uso terapêutico , COVID-19/tratamento farmacológico , Doença Enxerto-Hospedeiro/tratamento farmacológico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , SARS-CoV-2 , Transplante de Células-Tronco/efeitos adversos
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
10.
Med Oncol ; 37(5): 48, 2020 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-32277283

RESUMO

Therapy-related acute leukemias (t-ALs) represent approximately 10-20% of all acute leukemias, are frequently resistant to chemotherapy, and are associated with guarded outcomes. The national comprehensive cancer network data suggest that t-AL cases are diagnosed at increasing rates in breast cancer patients treated with chemotherapeutic agents targeting topoisomerase II. Two cases of BRCA1-mutated ovarian and breast carcinoma who developed therapy-related APL and ALL, respectively, following topoisomerase II-directed therapy were characterized. Genomic characterization of therapy-related acute promyelocytic leukemia (t-APL) revealed a unique RARA intron 2 breakpoint (Chr17: 40347487) at 3'-end of RARA corroborating breakpoint clustering in t-APL following topoisomerase II inhibition. Both cases of this series harbored germline BRCA1 mutations. The germline BRCA1 mutation in patient with t-APL was detected in exon 8 (HGVS nucleotide: c.512dupT). This mutation in t-APL is extremely rare. Interestingly, t-ALL patient in this series had a BRCA1 mutation (HGVS nucleotide: c.68_69delAG; BIC designation: 187delAG) identical to a previously reported case after the treatment of same primary disease. It is unlikely that two breast cancer patients with identical BRCA1 mutation receiving topoisomerase II-targeted agents for the primary disease developed t-AL by chance. This report highlights the development of t-AL in BRAC1-mutated hereditary breast and ovarian cancer patients and warrants further studies on functional consequences of topoisomerase inhibition in this setting.


Assuntos
Proteína BRCA1/genética , Carcinoma/tratamento farmacológico , Síndrome Hereditária de Câncer de Mama e Ovário/tratamento farmacológico , Leucemia Mieloide Aguda/induzido quimicamente , Inibidores da Topoisomerase II/efeitos adversos , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma/genética , Carcinoma/patologia , Feminino , Mutação em Linhagem Germinativa , Síndrome Hereditária de Câncer de Mama e Ovário/genética , Síndrome Hereditária de Câncer de Mama e Ovário/patologia , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Pessoa de Meia-Idade , Proteínas de Fusão Oncogênica/genética , Inibidores da Topoisomerase II/uso terapêutico , Translocação Genética , Resultado do Tratamento
11.
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
12.
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
13.
Indian J Pathol Microbiol ; 61(2): 209-213, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29676359

RESUMO

Introduction: Over the past decade, we have moved on from a predominantly morphological and clinical classification of myeloproliferative neoplasms (MPN) to a more evolved classification that accounts for the molecular heterogeneity that is unique to this subgroup of hematological malignancies. This usually incorporates mutations in Janus kinase 2 (JAK2), MPL, and calreticulin (CALR) genes. In this manuscript, we report the frequency of these mutations in a cohort of Indian patients at a tertiary cancer center. Materials and Methods: One hundred and thirty cases of MPN were included in this study. These cases were diagnosed and classified based on the World Health Organization 2008 criteria. JAK2 and MPL mutations were detected using high sensitivity allele-specific polymerase chain reaction using fluorescent labeled primers followed by capillary electrophoresis. A subset of JAK2 and CALR mutations were assessed using a fragment length assay. Results: Among the MPN, we had 20 cases of polycythemia vera (PV), 34 cases of essential thrombocythemia (ET), and 59 of myelofibrosis (MF). JAK2, MPL, and CALR mutations were mutually exclusive of each other. Seventeen cases were categorized as MPN unclassifiable (MPN-U). JAK2p.V617F and MPL mutations were present in 60% (78 of 130) and 5.3% (7 of 130) of all MPN. All the PV cases harbored the JAK2 p.V617F mutation. A total of 23.8% (31 of 130) of patients harbored CALR mutations. CALR exon 9 mutations were detected in 60.8% (14 of 23) and 50% (5 of 10) of JAK2 and MPL negative MF and ET cases, respectively. MPN-U cases included three JAK2 p.V617F positive, two MPL p.W515 L, and 12 CALR positive cases. Ten different types of CALR indels (8 deletions and 2 insertions) were detected of which Type I and Type II mutations were the most common, occurring at a frequency of 45.1% (14 of 31) and 22.5% (7 of 31), respectively. Discussion and Conclusion: We report frequencies of JAK2 p. V617F, MPL exon 10 and CALR mutations in 130 patients similar to those reported in western literature. These mutations carry not only diagnostic but also prognostic relevance.


Assuntos
Calreticulina/genética , Proteínas de Fusão bcr-abl/genética , Janus Quinase 2/genética , Transtornos Mieloproliferativos/genética , Receptores de Trombopoetina/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Mutação/genética , Policitemia Vera/genética , Mielofibrose Primária/genética , Estudos Retrospectivos , Trombocitemia Essencial/genética , Adulto Jovem
14.
Indian J Pathol Microbiol ; 61(1): 58-65, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29567885

RESUMO

Background: 2008 World Health Organization (WHO) classification of hematolymphoid neoplasms (HLN) has classified them based on morphology, results of various ancillary techniques, and clinical features.[1] There are no studies looking at the applicability of WHO classification. Aims: The aim of the study was to calculate proportions of all HLN subtypes seen during 1-year period based on 2008 WHO classification of HLN and study applicability and also shortcomings of practices in a tertiary care center in India. Materials and Methods: This was a 1-year retrospective study (January 1st, to December 31st, 2010) where cases were identified using hospital/laboratory electronic records. Old follow-up and referral cases were excluded from the study. Only newly diagnosed cases classified into categories laid down by 2008 WHO classification of HLN included. Results: Out of 2118 newly diagnosed classifiable cases, 1602 (75.6%) cases were of lymphoid neoplasms, 489 (23.1%) cases of myeloid neoplasms, 16 (0.8%) cases of histiocytic and dendritic cell neoplasms, and 11 (0.5%) cases of acute leukemias of ambiguous lineage. Overall, most common HLN subtype was diffuse large B-cell lymphoma (n = 361, 17.0%). Precursor B-lymphoblastic leukaemia/lymphoma (n = 177, 48.2%) was the most common subtype within pediatric age group. Conclusions: All major subtypes of HLN were seen at our center and showed trends almost similar to those seen in other Indian studies. Molecular/cytogenetic studies could not be performed on a significant number of cases owing to logistic reasons (unavailability of complete panels and also cost-related issues) and such cases could not be classified as per the WHO classification system.


Assuntos
Linfoma Difuso de Grandes Células B/classificação , Linfoma não Hodgkin/classificação , Organização Mundial da Saúde , Adolescente , Adulto , Criança , Feminino , Técnicas Histológicas , Humanos , Índia/epidemiologia , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/epidemiologia , Linfoma Difuso de Grandes Células B/fisiopatologia , Linfoma não Hodgkin/diagnóstico , Linfoma não Hodgkin/epidemiologia , Linfoma não Hodgkin/fisiopatologia , Masculino , Estudos Retrospectivos , Centros de Atenção Terciária , Adulto Jovem
15.
Mediterr J Hematol Infect Dis ; 10(1): e2018002, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29326799

RESUMO

Atypical breakpoints and variant APL cases involving alternative chromosomal aberrations are seen in a small subset of acute promyelocytic leukemia (APL) patients. Over seven different partner genes for RARA have been described. Although rare, these variants prove to be a diagnostic challenge and require a combination of advanced cytogenetic and molecular techniques for accurate characterization. Heterogeneity occurs not only at the molecular level but also at clinico-pathological level influencing treatment response and outcome. In this case series, we describe the molecular heterogeneity of APL with a focus on seven variant APL cases from a single tertiary cancer center in India over a period of two and a half years. We discuss five cases with ZBTB16-RARA fusion and two novel PML-RARA variants, including a Bcr3 variant involving fusion of PML exon4 and RARA exon3 with an additional 40 nucleotides originating from RARA intron2, another involving exon 6 of PML and exon 3 of RARA with addition of 126 nucleotides, which mapped to the central portion of RARA intron 2. To the best of our knowledge, this is the first case series of this kind from India.

16.
Indian J Med Paediatr Oncol ; 38(3): 394-397, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29200701

RESUMO

Mixed phenotype acute leukemia (MPAL) is a rare hematolymphoid neoplasm, representing only 3%-5% of acute leukemia. Although MPAL has been sufficiently described in the literature, its extramedullary presentation as a solitary lesion without leukemic (bone marrow [BM]) involvement is rarely described. We are presenting two cases of mixed phenotypic blastic hematolymphoid neoplasms without leukemic involvement at disease presentation in 8-year-old female and 21-year-old male patients. Both the cases had extralymphatic bone involvement in the form of solitary bone lesion. Initially, there was no leukemic involvement in both the cases, but the second case progressed to acute leukemia during the course of the disease. On immunophenotypic evaluation, both the cases revealed blasts showing unequivocal evidence of myeloid and B-lymphoid lineage commitment. These cases were difficult to categorize either into MPAL as the BM was not involved or into lymphoblastic lymphoma due to coexpression of myeloid differentiation. Therefore, we chose to classify them as a bi/mixed phenotypic blastic hematolymphoid neoplasm. Detailed immunophenotypic analysis either by immunohistochemistry or flow cytometric immunophenotyping is important for the diagnosis of such cases as they have a poor prognosis.

17.
Indian J Pathol Microbiol ; 60(2): 209-213, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28631637

RESUMO

INTRODUCTION: Copy number alterations (CNA) have been described in childhood precursor B-lineage acute lymphoblastic leukemia (B-ALL) which in conjunction with chromosomal abnormalities drive leukemogenesis. There is no consensus on the clinical incorporation of CNA in B-ALL. An integrated genomic classification (IGC) has been proposed which includes CNA and cytogenetics. METHODS: We correlated this IGC with immunophenotypic minimal residual disease (MRD) as well as other standard criteria for 245 patients of B-ALL such as National Cancer Institute (NCI) risk, D+8 prednisolone response, cytogenetics, and ploidy status. RESULTS: MRD was detectable in 81 patients (33.1%). The most common abnormalities were seen in CDKN2A/B (25.7%) followed by PAX5(20%), ETV6(16.7%), IKZF1(15.5%), Rb1(5.3%), BTG (3.3%), EBF1(2.0%), and PAR1(0.8%). On integrating CNA into the IGC, 170 patients (69.4%) were classified into good genomic risk (GEN-GR) whereas 75 (30.6%) belonged to the poor genomic risk (GEN-PR) category. The IGC showed a significant correlation with MRD and NCI risk. The presence of CNA predicted MRD clearance in intermediate cytogenetics group. CONCLUSION: These data seem to indicate that in addition to cytogenetics, CNA should be incorporated into routine clinical testing and risk algorithms for B-ALL. The IGC is of prognostic relevance and offers an additional avenue for prognostication and risk-adapted therapy.


Assuntos
Dosagem de Genes , Neoplasia Residual/diagnóstico , Patologia Molecular/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras B/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Neoplasia Residual/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia
18.
Indian J Pathol Microbiol ; 60(1): 38-42, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28195089

RESUMO

INTRODUCTION: Cytogenetic aberrations as well as presence of IGVH mutations are the underlying reason for clinical heterogeneity in Chronic Lymphocytic Leukemia (CLL). The presence of IGVH mutations as well as the predominant gene usage shows geographical variations. However, there is no study from India addressing immunogenetics of CLL. In a first Indian study we document the immunogenetics of CLL in a large tertiary hospital. METHODS: We analyzed IGVH mutation status, VH gene usage, cytogenetic abnormalities using FISH, immunophenotyping data and correlated them with standard clinical variables in 84 patients of CLL. RESULTS: Advanced Rai stage (Stage 3/4) was seen in 45% of our patients, where as 13q deletion was the commonest clonal cytogenetic abnormality detected in 48.4% of the cases. IGVH unmutated cases (55.2%) showed higher proportion expressing CD38 and CD49d, a preferential usage for VH1 and VH3 families (55.2%), presentation at an advanced Rai stage (52.8%) as well as more frequent presence of p53 deletions. As compared to the IGVH mutated cases greater proportion of IGVH unmutated patients (70%) required treatment. However, there was no significant difference in the time to treatment between mutated and unmutated cases which can be attributed to relatively short median follow up of 10 months. CONCLUSION: To summarize, we have seen a higher proportion of IGVH unmutated patients in our cohort (55.2%). The commonly used VH genes in the Indian population are IGVH 2-5, IGVH 1-2 and IGVH 1-69. Longer clinical follow up and a larger cohort is necessary to confirm the prognostic value of IGVH mutation analysis in Indian Patients with CLL.


Assuntos
Genótipo , Cadeias Pesadas de Imunoglobulinas/genética , Região Variável de Imunoglobulina/genética , Leucemia Linfocítica Crônica de Células B/genética , Leucemia Linfocítica Crônica de Células B/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Aberrações Cromossômicas , Citogenética , Feminino , Frequência do Gene , Técnicas de Genotipagem , Humanos , Imunofenotipagem , Índia , Masculino , Pessoa de Meia-Idade , Mutação , Centros de Atenção Terciária
19.
Indian J Pathol Microbiol ; 60(1): 84-86, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28195098

RESUMO

Chronic lymphocytic leukemia (CLL) is a common, immunophenotypically well-defined mature B-cell neoplasm. Demonstration of more than 5000/µL CD5+ B-cell population with co-expression of CD23, weak expression of CD20, and one type of immunoglobin light chain (either kappa or lambda) is necessary for the diagnosis of CLL. However, CLL with two populations of B-cells expressing both kappa as well as lambda (biclonal) light chains are extremely rare and has not been reported from India. We report two cases of biclonal CLL presented with leukocytosis, typical morphological features, and distinct immunophenotype of CLL. These cases are also an example which suggests that careful attention to the morphology of the blood smear and the entire immunophenotype panel is a must and will aid the proper diagnosis as only light chain ratios can be misguiding.


Assuntos
Linfócitos B/química , Linfócitos B/classificação , Cadeias kappa de Imunoglobulina/análise , Cadeias lambda de Imunoglobulina/análise , Leucemia Linfocítica Crônica de Células B/diagnóstico , Leucemia Linfocítica Crônica de Células B/patologia , Adulto , Idoso , Humanos , Imunofenotipagem , Índia , Masculino
20.
Cytometry B Clin Cytom ; 92(4): 315-318, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-27018867

RESUMO

BACKGROUND: CD19 is a B-cell specific marker, expressed on all stages of B-lymphocytes including plasma cells. It is widely used in the flow cytometric immunophenotyping (FCI) of B-cell and plasma cell malignancies. The analysis approach of FCI for the diagnosis and monitoring of B-cell acute lymphoblastic leukemia (B-ALL) is totally based on the CD19-based primary gating strategy and it would be challenging to study B-ALL without CD19 expression. Since CD19 negative B-ALL are extremely rare, we report three cases of B-ALL with negative expression of CD19 and discussed its implication in the diagnosis, residual disease monitoring and future targeted therapy. METHODS: Peripheral blood (PB) and bone marrow (BM) samples from three cases suspicious of acute leukemia were studied for morphology, cytochemistry, immunophenotyping and cytogenetics. FCI was performed using a comprehensive six to eight-color multiparametric assay. The cytogenetic studies for standard recurrent genetic translocations were performed by FISH & Karyotyping. RESULTS: The three cases studied were diagnosed as B-ALL based on the expression of CD10, CD20, CD22, CD34, and CD79a by leukemic blasts. CD19 was studied using two different clones (i.e. J3-119 & HIB-19) and found to be severely down regulated in all three cases. There were no significant differentiating features in morphology. Cytogenetic studies were negative for recurrent translocations. CONCLUSION: We report three cases of extremely rare CD19 negative B-ALL. Lack of awareness of negative CD19 expression in B-ALL can leads to incorrect immunophenotypic diagnosis and monitoring of B-ALL, especially in laboratories using limited markers. © 2016 International Clinical Cytometry Society.


Assuntos
Antígenos CD19/genética , Linfócitos B/patologia , Células da Medula Óssea/patologia , Imunofenotipagem/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Adulto , Anticorpos/química , Antígenos CD/genética , Antígenos CD/imunologia , Antígenos CD19/imunologia , Linfócitos B/imunologia , Células da Medula Óssea/imunologia , Criança , Pré-Escolar , Regulação para Baixo , Feminino , Citometria de Fluxo , Expressão Gênica , Humanos , Cariotipagem , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia
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