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1.
Blood ; 120(26): 5181-4, 2012 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-23091298

RESUMO

To ascertain the genetic basis of pediatric Burkitt lymphoma (pBL), we performed clinical-grade next-generation sequencing of 182 cancer-related genes on 29 formalin-fixed, paraffin embedded primary pBL samples. Ninety percent of cases had at least one mutation or genetic alteration, most commonly involving MYC and TP53. EBV(-) cases were more likely than EBV(+) cases to have multiple mutations (P < .0001). Alterations in tumor-related genes not previously described in BL were identified. Truncating mutations in ARID1A, a member of the SWI/SNF nucleosome remodeling complex, were seen in 17% of cases. MCL1 pathway alterations were found in 22% of cases and confirmed in an expanded panel. Other clinically relevant genomic alterations were found in 20% of cases. Our data suggest the roles of MCL1 and ARID1A in BL pathogenesis and demonstrate that comprehensive genomic profiling may identify additional treatment options in refractory disease.


Assuntos
Proteínas Reguladoras de Apoptose/genética , Linfoma de Burkitt/genética , Montagem e Desmontagem da Cromatina/genética , Mutação , Análise de Sequência de DNA/métodos , Adolescente , Apoptose/genética , Linfoma de Burkitt/diagnóstico , Criança , Pré-Escolar , Montagem e Desmontagem da Cromatina/fisiologia , Frequência do Gene , Genes Neoplásicos/genética , Genoma/genética , Genômica/métodos , Humanos , Lactente , Mutação/fisiologia , Adulto Jovem
2.
Hematol Oncol ; 31(1): 49-53, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22618860

RESUMO

Post-transplant lymphoproliferative disorders of T-cell origin are quite uncommon, and the vast majority represent neoplasms of mature, post-thymic T- or natural killer cells. Here, we report a rare case of T-cell acute lymphoblastic leukaemia (T-ALL), which occurred in an 18-year-old man who had undergone three liver transplants, initially for biliary atresia and subsequently for graft failure due to chronic rejection. He had received immunosuppression with cyclosporine and tacrolimus, as well as short-term treatment with OKT3. The T-ALL occurred 16 years after the first liver transplant. This case highlights the challenge for classifying rare neoplasms occurring in recipients of solid organ transplants that are currently not recognized to lie within the spectrum of post-transplant lymphoproliferative disorders. Given the long interval between the liver transplants and the development of T-ALL, a coincidental occurrence of the leukaemia cannot be ruled out. However, the potential roles of immunosuppressive therapy and other co-morbid conditions of the individual as possible risk factors for the pathogenesis of T-ALL are discussed.


Assuntos
Transplante de Fígado , Complicações Pós-Operatórias/etiologia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/etiologia , Adolescente , Atresia Biliar/cirurgia , Causalidade , Células Clonais/patologia , Comorbidade , Ciclosporina/efeitos adversos , Ciclosporina/uso terapêutico , Diagnóstico Diferencial , Suscetibilidade a Doenças , Rearranjo Gênico da Cadeia beta dos Receptores de Antígenos dos Linfócitos T , Rejeição de Enxerto/tratamento farmacológico , Rejeição de Enxerto/cirurgia , Humanos , Hospedeiro Imunocomprometido , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Leucemia Induzida por Radiação/diagnóstico , Transtornos Linfoproliferativos/diagnóstico , Masculino , Muromonab-CD3/efeitos adversos , Muromonab-CD3/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/imunologia , Radiografia/efeitos adversos , Indução de Remissão , Reoperação , Tacrolimo/efeitos adversos , Tacrolimo/uso terapêutico , Fatores de Tempo
3.
J Hematol Oncol ; 8: 94, 2015 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-26219558

RESUMO

Bcl11b is a transcription factor important for T cell development and also a tumor-suppressor gene that is hemizygously inactivated in ~10% human T cell acute lymphoblastic leukemia (T-ALL) and several murine T-ALL models, including ATM(-/-) thymic lymphomas. Here we report that heterozygous loss of Bcl11b (Bcl11b(+/-)) unexpectedly reduced lethal thymic lymphoma in ATM(-/-) mice by suppressing lymphoma progression, but not initiation. The suppression was associated with a T cell-mediated immune response in ATM(-/-)Bcl11b(+/-) mice, revealing a haploid insufficient function of Bcl11b in immune modulation against lymphoma and offering an explanation for the complex relationship between Bcl11b status with T-ALL prognosis.


Assuntos
Haploinsuficiência/imunologia , Linfoma de Células T/imunologia , Proteínas Repressoras/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Animais , Progressão da Doença , Regulação da Expressão Gênica , Humanos , Linfoma de Células T/patologia , Camundongos
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