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Rarely, immunophenotypically immature B-cell precursor acute lymphoblastic leukemia (BCP-ALL) carries an immunoglobulin- MYC rearrangement (IG-MYC-r). This can result in diagnostic confusion with Burkitt lymphoma/leukemia and use of individualized treatment schedules of unproven efficacy. Here we compare the molecular characteristics of these conditions and investigate historic clinical outcome data. We identified 90 cases registered in a national BCP-ALL clinical trial/registry. When present, diagnostic material underwent cytogenetic, exome, methylome and transcriptome analyses. The outcomes analyzed were 3-year event-free survival and overall survival. IG-MYC-r was identified in diverse cytogenetic backgrounds, co-existing with either established BCP-ALL-specific abnormalities (high hyperdiploidy, n=3; KMT2A-rearrangement, n=6; iAMP21, n=1; BCR-ABL1, n=1); BCL2/BCL6-rearrangements (n=15); or, most commonly, as the only defining feature (n=64). Within this final group, precursor-like V(D)J breakpoints predominated (8/9) and KRAS mutations were common (5/11). DNA methylation identified a cluster of V(D)J-rearranged cases, clearly distinct from Burkitt leukemia/lymphoma. Children with IG-MYC-r within that subgroup had a 3-year event-free survival of 47% and overall survival of 60%, representing a high-risk BCP-ALL. To develop effective management strategies this group of patients must be allowed access to contemporary, minimal residual disease-adapted, prospective clinical trial protocols.
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Linfoma de Burkitt , Leucemia-Linfoma Linfoblástico de Células Precursoras B , Criança , Humanos , Linfoma de Burkitt/diagnóstico , Linfoma de Burkitt/genética , Linfoma de Burkitt/terapia , Estudos Prospectivos , Imunoglobulinas/genética , Rearranjo Gênico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapiaRESUMO
Extrapulmonary DICER1-associated sarcomas (DS) can harbor morphological features overlapping with pleuropulmonary blastoma. We report three children with intracranial and genital tract sarcomas, suspected to have DS based on a heterogeneous yet defining combination of spindle-cell sarcomatous and blastemal morphology, with rhabdomyomatous differentiation. Foci of immature cartilage at diagnosis (n = 2/3) and increased neuroepithelial differentiation at recurrence (n = 1) were noted. Morphological suspicion prompted somatic testing at reference centers, confirming likely biallelic, loss-of-function, and "hotspot" missense DICER1 variants in all three tumors. This can serve as a model for this diagnosis in resource-limited settings and has implications for germline testing, surveillance, and tumor management.
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Blastoma Pulmonar , Sarcoma , Neoplasias de Tecidos Moles , Criança , RNA Helicases DEAD-box/genética , Países em Desenvolvimento , Mutação em Linhagem Germinativa , Humanos , Blastoma Pulmonar/diagnóstico , Blastoma Pulmonar/genética , Blastoma Pulmonar/patologia , Ribonuclease III/genética , Sarcoma/diagnóstico , Sarcoma/genética , Sarcoma/patologiaRESUMO
The feasibility of bortezomib (BZB) in induction and reduced cytarabine doses in intensification was evaluated in children with relapsed acute lymphoblastic leukaemia (rALL) at a single centre in India. Of 55 children with rALL, 23 received supportive care and 7 refused treatment, with a median survival of 2 (interquartile range 1-6) months. Twenty-two (88%) of 25 children who were treated achieved second remission and 9 (69%) of 13 had end-of-induction minimal residual disease of <10-4 . The lower cytarabine dose was associated with decreased hospitalisation. One-year event-free and overall survival for the treated group was 74·7% (95% confidence interval 52-88) and 79·6% (58-91) respectively.
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Adolescente , Bortezomib/administração & dosagem , Criança , Pré-Escolar , Citarabina/administração & dosagem , Intervalo Livre de Doença , Feminino , Humanos , Índia/epidemiologia , Lactente , Masculino , Neoplasia Residual , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangue , Taxa de SobrevidaRESUMO
Karyotyping along with a 3-probe fluorescence in situ hybridization (FISH) strategy was used to risk stratify therapy in 303 children with B-cell precursor acute lymphoblastic leukaemia. Of the 166 patients risk stratified, karyotype identified 91 (55%). FISH identified all karyotypes accurately, with the exception of hypodiploidy, and risk stratified an additional 75 patients. The frequency of ETV6-RUNX1 is lower and high hyperdiploidy, higher than reported in the west. An adapted 3-probe FISH strategy identified two patients with ETV6-ABL1 fusion who received imatinib. In limited-resource settings, a 3-probe FISH approach provides a practical approach for risk-stratified therapy in childhood ALL.
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Subunidade alfa 2 de Fator de Ligação ao Core/genética , Hibridização in Situ Fluorescente , Cariotipagem , Proteínas de Fusão Oncogênica/genética , Ploidias , Leucemia-Linfoma Linfoblástico de Células Precursoras B/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Mesilato de Imatinib/administração & dosagem , Lactente , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamento farmacológico , Medição de RiscoRESUMO
An infant presented with fever and purulent discharge from the left ear, proptosis of the right eye, and hepatosplenomegaly. She was diagnosed with acute monoblastic leukemia on morphological and flowcytometric analysis of the bone marrow. Karyotyping showed a jumping translocation (JT) involving the long arm of chromosome 1 as the sole cytogenetic abnormality in 29 metaphases. The patient died within 2 months of diagnosis. The presence of JT in a de novo infant AML as a sole cytogenetic abnormality indicates its possible role in leukemogenesis unlike previous reports that have implicated its role in tumor progression only.
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Aberrações Cromossômicas , Cromossomos Humanos Par 1/genética , Leucemia Mieloide Aguda/genética , Translocação Genética/genética , Feminino , Humanos , Hibridização in Situ Fluorescente , Lactente , Cariotipagem , Leucemia Mieloide Aguda/patologia , PrognósticoRESUMO
BACKGROUND: The role of ETV6 in B-cell acute lymphoblastic leukemia (ALL) has been extensively studied, whereas only rare cases of ETV6 involvement in pediatric T-cell ALL have been described. OBSERVATION: We report a case of T-cell ALL in a 13-year-old boy with t(2;12)(q31;p13) involving ETV6, resulting in the relocation of the ETV6 from 12p13 to 2q31 locus that harbors the class 1 homeobox gene (HOX) cluster D, which is expressed during the early stages of T-cell development. CONCLUSIONS: We report a novel translocation in T-cell ALL highlighting the involvement of ETV6 and potentially the HOXD gene cluster in a case of T-cell ALL.
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Cromossomos Humanos Par 12/genética , Cromossomos Humanos Par 2/genética , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Proteínas de Fusão Oncogênica/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Translocação Genética/genética , Adolescente , Citometria de Fluxo , Humanos , Hibridização in Situ Fluorescente , Masculino , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia , PrognósticoAssuntos
Células da Medula Óssea/metabolismo , Vesículas Extracelulares/metabolismo , Células-Tronco Mesenquimais/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras B/metabolismo , Animais , Antígenos CD19/metabolismo , Linhagem Celular , Linhagem Celular Tumoral , Endocitose , Humanos , Camundongos Endogâmicos NOD , Camundongos Knockout , Camundongos SCID , Microscopia Confocal , Transplante HeterólogoRESUMO
Chromosomal abnormalities are seen in nearly 1% of live born infants. We report a 5-year-old boy with the clinical features of Down syndrome, which is the most common human aneuploidy. Cytogenetic analysis showed a mosaicism for a double aneuploidy, Down syndrome and XYY. The karyotype was 47, XY,+21[19]/48, XYY,+21[6]. ish XYY (DXZ1 × 1, DYZ1 × 2). Mosaic double aneuploidies are very rare and features of only one of the aneuploidies may predominate in childhood. Cytogenetic analysis is recommended even if the typical features of a recognized aneuploidy are present so that any associated abnormality may be detected. This will enable early intervention to provide the adequate supportive care and management.
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INTRODUCTION: High-dose chemotherapy with melphalan, followed by autologous hematopoietic stem cell transplantation (AHCT) remains the standard of care for consolidation therapy of fit patients with newly diagnosed multiple myeloma (NDMM), for more than 20 years now. MATERIAL AND METHODS: This is a retrospective study of NDMM patients who underwent AHCT at our center from 2011 to 2018. Data was undertaken using the hospital electronic medical records (EMR). RESULTS: Among transplant eligible patients (which were 764), 78 patients (10.2%) underwent AHCT. The predominant stage in the study cohort was International Scoring System (ISS)-III (55%), and IgG-kappa (44%) was the commonest subtype of multiple myeloma (MM). Light chain myeloma was found in 23.5% of patients. Pretransplant, 42%, 48%, and 10% patients were in more than very good partial response (>VGPR), very good partial response (VGPR), and partial response (PR), respectively. The median duration of follow-up was 57.2 months (range: 12.1-120.2 months). The entire cohort's 5-year overall survival (OS) and progression-free survival (PFS) were 89.1% and 41.8%, respectively. CONCLUSION: Bortezomib based triplet induction regimens were effective and well tolerated in this retrospective analysis of Indian patients. We observed that AHCT effectively achieves deep and durable remission in MM.
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Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Humanos , Bortezomib/uso terapêutico , Quimioterapia de Indução , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/tratamento farmacológico , Estudos RetrospectivosRESUMO
A case of signet ring cell lymphoma of presacral lymph node is reported. The patient was diagnosed as follicular lymphoma on the basis of clinical and laboratory features, including immunohistochemistry (IHC) and gene rearrangement studies. Light microscopy examination showed neoplastic atypical cells with signet ring cell morphology in core biopsy of lymph node that stained for B-cell markers by IHC. In addition, the neoplastic cells expressed CD20, CD10, BCL-2, and BCL-6, indicating follicular center origin. Fluorescence in situ hybridization study demonstrated BCL2 gene arrangement. Especially in the case of deep-seated intra-abdominal lymph nodes with atypical presentation, the differential diagnosis arises with nonhemopoietic tumors, and this needs to be distinguished by specific immunostaining and gene arrangement studies.
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Carcinoma de Células em Anel de Sinete , Linfoma Folicular , Carcinoma de Células em Anel de Sinete/diagnóstico , Carcinoma de Células em Anel de Sinete/genética , Carcinoma de Células em Anel de Sinete/patologia , Rearranjo Gênico , Humanos , Hibridização in Situ Fluorescente , Linfoma Folicular/diagnóstico , Linfoma Folicular/genética , Linfoma Folicular/patologia , Proteínas Proto-Oncogênicas c-bcl-2/genéticaRESUMO
BACKGROUND: Mantle cell lymphoma (MCL) is a rare type of mature B-cell lymphoid malignancy with the pathologic hallmark of translocation t(11;14) (q13, q32), which leads to an overexpression of Cyclin D1 (CCND1). The disease is also characterized by the presence of a high number of recurrent genetic alterations, which include aberrations in several cellular pathways. MCL is a heterogeneous disease with a wide range of clinical presentations and a majority presenting with aggressive disease in advanced stages. RECENT FINDINGS: Management of MCL is bereft with challenges due to its resistant and relapsing pattern. Despite improvements in remission durations, the disease is currently incurable with standard therapy and has a median survival of about 3-5 years. The use of small molecules like the bruton tyrosine kinase (BTK) and BCL2 inhibitors, for treating relapsed MCL has been established leading to a diminishing role for conventional chemotherapy. Combinations of small molecule inhibitors with or without chemoimmunotherapy, are showing promising results. Cellular therapy in the form of CAR-T cell therapy, has been approved recently. CONCLUSIONS: Personalized cancer treatment and chemo-free regimens are showing promise and results from well-planned long-term studies are evolving. In India, there is a paucity of epidemiological, clinical, and research data in this field.
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Antineoplásicos , Linfoma de Célula do Manto , Adulto , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Humanos , Imunoterapia Adotiva , Índia/epidemiologia , Linfoma de Célula do Manto/tratamento farmacológico , Linfoma de Célula do Manto/terapiaRESUMO
PURPOSE: There are limited reports of quality metrics in glioblastoma. We audited our adherence to quality indicators as proposed in the PRIME Quality Improvement study. METHODS: This is a retrospective audit of patients treated between 2017 and 2020. After postsurgical integrated diagnosis, patients received radiotherapy (RT) with concurrent and adjuvant temozolomide (TMZ). Multiparametric magnetic resonance imaging at predefined times guided management. Numbers with proportions for indices were calculated. Survival was estimated using the Kaplan-Meier method. RESULTS: One hundred six patients were consecutively treated. The median age was 55 years (interquartile range of 47-61 years) with a male preponderance (68%). Ninety-six (90.6%) patients underwent subtotal resection, and 10 (9.4%) biopsy alone. Isocitrate dehydrogenase was wild-type in 96 (91%), and O6-methylguanine-DNA methyltransferase was unmethylated in 70 (66.0%) patients. Telomerase reverse transcriptase promoter was mutated in 64 (60.4%), and TP53 was mutated in 22 (20.8%). Concurrent radiation and TMZ were planned for 104 (98.1%), and radiation alone for 2 (1.9%). The median time to concurrent RT-TMZ was 36 days (interquartile range 30-44 days). All patients planned for RT-TMZ completed treatment, but only 81 (76%) completed adjuvant TMZ. Sixty-three (59%) completed six cycles, 18 (17%) received less than six cycles, and 25 (24%) did not receive adjuvant TMZ. At a median follow-up of 24 months (range 21-31 months), the median (95% CI) progression-free survival and overall survival were 11 (95% CI, 9.4 to 13.0) and 20.0 (95% CI, 15 to 26) months, respectively. CONCLUSION: Our patients met quality indices in most domains; outcomes are comparable with global results. Metrics will be periodically evaluated to include new standards and assess continuous service appropriateness.
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Neoplasias Encefálicas , Glioblastoma , Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Dacarbazina/uso terapêutico , Glioblastoma/tratamento farmacológico , Glioblastoma/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Indicadores de Qualidade em Assistência à Saúde , Estudos Retrospectivos , Temozolomida/uso terapêutico , Atenção Terciária à SaúdeRESUMO
Hypodiploidy with < 40 chromosomes is associated with poor prognosis in B cell precursor acute lymphoblastic leukemia. In some patients, the hypodiploid clone undergoes endoreduplication, resulting in doubling of the number of chromosomes and masquerades as a high hyperdiploid BCP-ALL. Karyotyping reveals metaphases with 50-79 chromosomes masking the hypodiploid clone. Identifying hypodiploidy in such cases requires awareness of non random alterations of chromosomal copy numbers found in hypodiploid BCP-ALL. We used a systematic strategy to identify masked hypodiploidy integrating targeted fluorescence in situ hybridization (FISH) analysis directed towards identifying monosomies of chromosomes 7, 15 and 17 and flow cytometry-based ploidy analysis (FCPA). Of 445 patients diagnosed as BCP ALL, 2.9% (13/445) were classified as hypodiploid including patients with masked hypodiploidy. Karyotype analysis showed hypodiploidy in 3 patients, near triploidy in 4 patients and normal karyotype in 6 patients. Four patients with near triploid clone on karyotype showed either bimodal peak (2 patients) or single low hypodiploid peak (1 patient) or only near triploid peak (1 patient) on FCPA. All 6 patients with normal karyotype revealed either bimodal peak (4 patients) or hypodiploid peak (2 patients) on FCPA. Targeted FISH analysis unmasked hypodiploid clone showing monosomies of chromosomes 7, 15 and 17 in all ten patients. Our algorithm successfully identified masked hypodiploidy in patients, including those with endoreduplication (4 patients) and normal karyotype (6 patients). Integrating FCPA with targeted FISH analysis provides a practical, sensitive and specific approach to identify masked hypodiploidy in low resource settings.
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INTRODUCTION: Despite high cure rates with standard treatment, 30% patients with Hodgkin lymphoma develop relapsed or refractory (R/R) disease. Salvage therapy followed by autologous hematopoietic cell transplantation (HCT) is considered standard of care. Brentuximab Vedotin (Bv) in combination with Bendamustine (B) has been tested in the salvage setting with promising results. MATERIALS AND METHODOLOGY: We conducted a single centre retrospective chart review of patients who received BBv salvage therapy to determine its activity and safety in patients with R/R classical Hodgkin lymphoma (HL). Between May 2011- December 2019, 179 patients were diagnosed with R/R HL. RESULTS: Thirty patients received BBv [median age: 30 (15-59) years, females (n=15)]. Primary refractory disease in 19 patients (63%), and 26 patients (87%) had advanced stage at treatment. Most patients received BBv after 2 prior lines of therapy [n=16 (53%)]. The median number of cycles of BBv were 3 (1-6). The number of BBv cycles delivered as outpatient was 63%. The most common Grade III/IV hematological adverse event was neutropenia [n=21, (70%)], while grade III/IV non-hematological toxicities included infections in 4 (13%), neuropathy in 4(13%), skin rash in 2 (7%), GI toxicities in 3 (10%) and liver dysfunction in 2 (7%) patients. The ORR and CR rates were 79% and 62%, respectively. Seventeen patients (57%) underwent an autologous HCT and 8 (26%) underwent an Allogeneic HCT (all haploidentical). The median follow up time from BBv administration was 12 months. Six patients died: 2 = disease progression, and 4 = non-relapse causes (Infection and sepsis = 2, GVHD=2). In addition to this, one patient progressed soon after HCT and another patient relapsed 22 months post HCT. Three year Overall survival (OS) and Event free survival (EFS) probability post-BBv treatment was 75% and 58%, respectively. OS and EFS analysis based on response (viz., CMR) to BBv demonstrated that patients in CMR had better survival probability [93% (p=0.0022) 3yr-OS and 72% (p=0.038) 3yr-EFS probability]. CONCLUSIONS: BBv is an active and well-tolerated salvage treatment for patients with R/R HL, even in refractory and advanced settings. In middle-income settings, cost constraints and access determine patient uptake of this regimen.
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OBJECTIVE: Tobacco consumption is one of the major etiological factors for oral cancer, but it also develops in non-tobacco users, with unknown etiologies. Cellular models for tobacco associated oral cancer are available, however; reports of cellular models for studying non-tobacco associated oral cancer are limiting. We report here the establishment and characterization of two novel buccal mucosal cancer cell lines 'GBC02' and 'GBC035' derived from non-tobacco users. MATERIALS AND METHODS: Short tandem repeats (STR) profiling, Next-generation sequencing for whole-genome, exome and copy number alterations, immunofluorescence, flow-cytometry, proliferation, live-cell chemotaxis, 3D-spheroid formation, chemotherapy response, gene-expression microarray, gene-set enrichment analysis and xenograft development were performed. RESULTS: Sources of the established cultures were matched to their donors through STR profiling. Genome sequence analysis revealed somatic mutations in TP53, CASP8, CDKN2A for GBC02 with deletions and amplifications encompassing CDKN2A, FAT1 and CCND1, PIK3CA, SOX2, EGFR, MYC genes, respectively. GBC035 harbored mutations in FAT1, NOTCH1, HRAS, CDKN2A, HLA-B, HLA-A genes. While GBC035 cells showed higher E-Cadherin positive cell-cell junctions and collective cell migration in chemotaxis; GBC02 cells were vimentin-positive and demonstrated individual cell migration. Further, exhibiting their relevance to preclinical research, GBC02 3D-spheroids demonstrated enrichment of development-related gene-signatures in microarray transcriptome analysis and were resistant to Cisplatin, but showed sensitivity to cancer stem cells-targeting drug, Salinomycin. Additionally, tumorigenic ability of GBC02 was demonstrated. CONCLUSIONS: Altogether, we present here comprehensively characterized unique cell lines established from non-tobacco associated tumors, which may serve as models for preclinical investigations of oral cancers caused independent of tobacco usage.
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Neoplasias Bucais/etiologia , Fumar Tabaco/efeitos adversos , Uso de Tabaco/efeitos adversos , Técnicas de Cultura de Células , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa Bucal , Neoplasias Bucais/patologiaRESUMO
INTRODUCTION: Approximately 35% of NSCLC patients in East Asia have EGFR mutations. Next-generation sequencing (NGS) provides a comprehensive mutational profile in lung cancer patients. MATERIAL AND METHOD: Clinicopathologic characteristics and mutational profiling data was analyzed from nonsmall cell lung carcinoma /Adenocarcinoma over a duration of 42 months (October 2014 to March 2018) using next-generation sequencing Ion Ampliseq Cancer Hotspot panel v2 (Ampliseq, Life Technologies) on the Ion torrent PGM platform. RESULTS: A total of 154 cases were processed during this period. The average number of mutations/case varied from one to four 72.07% (111/154), of these cases had minimum one genetic alteration. The most common mutated gene was TP53 gene (37.6%, nâ¯=â¯58) followed by EGFR (32.4%, nâ¯=â¯50), KRAS (18.18%, nâ¯=â¯28), ERBB2 (3.2%, nâ¯=â¯5), BRAF (1.94%, nâ¯=â¯3). EGFR positivity was more in females (43.3%) and non-smokers (52.08%) in comparison to males (26.7%) and smokers (16.1%). CONCLUSION: In this paper, we have described the comprehensive mutational profiling of a large cohort of advanced lung adenocarcinoma patients from the eastern part of India. To the best of our knowledge, this is one of the largest studies from the country describing mutations in BRAF, ERBB2, TP53 genes and their clinicopathologic/histopathologic associations in lung cancers.
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Adenocarcinoma de Pulmão/patologia , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Neoplasias Pulmonares/patologia , Mutação , Adenocarcinoma de Pulmão/epidemiologia , Adenocarcinoma de Pulmão/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Feminino , Seguimentos , Humanos , Índia/epidemiologia , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Adulto JovemRESUMO
Acute promyelocytic leukemia (APML) with variant RARa translocations comprises 1-2% of APML cases. However, the diagnosis of these cases is challenging as the routine practice includes fluorescence in situ hybridization (FISH) reverse transcription polymerase chain reaction targeting the PML and RARA genes to detect PML/RARA fusions. Here, we report a case highlighting the importance of atypical FISH signal patterns in standard dual-color dual-fusion PML/RARa FISH analysis complimented by karyotyping to detect these variant RARA translocations.
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Hibridização in Situ Fluorescente , Leucemia Promielocítica Aguda , Proteínas de Fusão Oncogênica/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Translocação Genética , Adulto , Humanos , Leucemia Promielocítica Aguda/diagnóstico , Leucemia Promielocítica Aguda/genética , Leucemia Promielocítica Aguda/patologia , MasculinoRESUMO
Recurrent mutations affecting MYD88 and CXCR4 gene nowadays form the basis for the diagnosis, risk stratification and use of inhibitors targeting these signalling pathways in LPL/WM which are rare B cell neoplasms. MYD88 L265P mutation analysis was performed on 33 cases of LPL/WM by AS-PCR (positivity-84.8%, n = 28/33) and by Sanger sequencing (positivity-39.3%, n = 13/33). We had only two cases with CXCR4 non-sense (NS) mutation (p.S338*) using Sanger sequencing. MYD88 (L265P) mutation detection by AS-PCR can form reliable biomarker for the diagnosis of LPL/WM in molecular labs. Although the cohort is small, still the CXCR4 mutation frequency in our study is low as compared to the published literature.
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BACKGROUND: Flow cytometry (FCM) is a simple, sensitive, and specific technique that can potentially determine DNA ploidy in B-cell precursor ALL (BCP-ALL) and is complementary to cytogenetics. METHODS: A prospective FCM DNA ploidy analysis using FxCycle™ Violet (assay sensitivity 0.01%) was done in 125 consecutive new cases of BCP-ALL (90 cases <15 years of age) and compared with corresponding cytogenetic ploidy (karyotyping and/or FISH) data wherever available. This assay was also subsequently evaluated for detection of residual aneuploid clone in few BCP-ALL cases. RESULTS: Of the total 125 BCP-ALL cases evaluated, flow ploidy analysis revealed diploidy (DI 0.96-1.05) in 44.8% (n = 56), low-hyperdiploidy (DI 1.06 to 1.15) in 13.6% (n = 17), high-hyperdiploidy (DI 1.16-1.39) in 32.8% (n = 41) and near-tetraploidy (DI ≥ 1.80) in 2.4% (n = 3) cases. The high risk sub-group of low-hypodiploidy (DI 0.70 to 0.88)/near-triploidy (DI 1.40 to 1.79) constituted 5.6% (n = 7) cases while there was only one case with haploidy (DI 0.58). Overall, high concordance of 90.4% (n = 113) was noted between the combined cytogenetics ploidy and FCM ploidy. Of the total discordant cases (n = 12), the maximum discordance was seen in the low-hyperdiploid DI subgroup (n = 10), which included seven cases with low DNA index high hyperdiploidy (LDI-HHD). FCM DNA ploidy assay was able to detect the residual clone in all six MRD positive aneuploid cases evaluated. CONCLUSIONS: FxCycle™ based DNA ploidy ascertains strong correlation with cytogenetic profiles and yields complementary information that can be used by the cytogenetics laboratories or otherwise. © 2019 International Clinical Cytometry Society.
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Aneuploidia , Análise Citogenética , Citometria de Fluxo , Neoplasia Residual/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Imunofenotipagem , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto JovemRESUMO
BACKGROUND: For diagnosis, sub-categorization and follow up of Acute Leukemia (AL), phenotypic analysis using flow cytometry is mandatory. MATERIAL AND METHODS: We retrospectively analyzed immunophenotypic data along with cytogenetics/molecular genetics data (wherever available) from 631 consecutive cases of AL diagnosed at our flow cytometry laboratory from January 2014 to August 2017. RESULTS: Of the total 631 cases, 52.9% (n=334) were acute lymphoblastic leukemia (ALL), 43.9% (n=277) acute myeloid leukemia (AML), 2.2% (n=14) mixed phenotypic acute leukemia (MPAL), 0.5% (n=3) acute undifferentiated leukemia (AUL) and 0.5% (n=3) chronic myeloid leukemia in blast crisis (CML-BC). ALL cases comprised of 81.7% (n=273/334) B-cell ALLs (95.2%, n=260/273 common B-ALLs and 4.8%, n=13/273 Pro B-ALLs). CD13 was the commonest cross lineage antigen, expressed in B-ALL (25.6%, n=70/273), followed by CD33 (17.9%, n=49) and combined CD13/CD33 (11.3%, n=31/273) expression. T-ALLs constituted 18.3% (n=61/334) of total ALLs and included 27.9% (n=17/61) cortical T- ALLs. CD13 was commonest (32.7%, n=20/61) aberrantly expressed antigen in T-ALLs, followed by CD117 (19.1%, n=9/47). AML cases included 32.1% (n=89/277) AML with recurrent genetic abnormalities, 9.0% (n=25/277) with FLT3/NPM1c mutation and 58.9% (n=163/277) AML NOS including 14.7% (n=24/163) AML M4/M5, 1.8% (n=3/163) AML M6 and 3.7% (n=6/163) AML M7. In AMLs, CD19 aberrancy was the most common (20.2%, n=56/277) followed by CD56 (15.8%, n=42/265). CONCLUSIONS: In this study, we document the spectrum, correlate the immunophenotype with genetic data of all leukemias, especially concerning T-ALL where the data from India is scarce.