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1.
Am J Clin Pathol ; 144(2): 305-14, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26185316

RESUMO

OBJECTIVES: Abnormalities of the RUNX1 gene in childhood B-acute lymphoblastic leukemia (B-ALL) are manifested by ETV6-RUNX1 or RUNX1 amplification. A detailed comparison between the two regarding clinicopathologic features with genetic analysis has not been performed previously. This parallel study assessed how different RUNX1 abnormalities affect the clinicopathology of B-ALL. METHODS: We compared clinicopathologic factors, including age, sex, WBC count, cerebrospinal fluid (CSF) involvement, immunophenotype, and blast proliferation rate between B-ALL with RUNX1 amplification (10 cases) and B-ALL with ETV6-RUNX1 translocation (67 cases) in childhood B-ALL. RESULTS: CD7 was often expressed in RUNX1 amplification but not in ETV6-RUNX1 (44% vs 0%, P = .0001) and appeared to correlate with CSF involvement in the former group (3/4 [75%]). CD13 was often detected in ETV6-RUNX1 with additional RUNX1 gain (38%) with an even higher frequency in double ETV6-RUNX1 translocation (77%), but was not detected in RUNX1 amplification (0%, P < .05). Children with RUNX1 amplification were older and more often CSF positive, while those with ETV6-RUNX1 were younger, more frequently had hyperleukocytosis, and had higher blast proliferation rates. CONCLUSIONS: RUNX1 copy numbers seem to be proportional to the age of B-ALL onset and the frequency of CSF involvement, while RUNX1 amplification vs translocation causes aberrant expression of CD7 and CD13, respectively.


Assuntos
Subunidade alfa 2 de Fator de Ligação ao Core/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Adolescente , Idade de Início , Animais , Antígenos CD7/biossíntese , Antígenos CD7/imunologia , Antígenos CD13/biossíntese , Antígenos CD13/imunologia , Pré-Escolar , Feminino , Citometria de Fluxo , Amplificação de Genes , Humanos , Imunofenotipagem , Hibridização in Situ Fluorescente , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/líquido cefalorraquidiano , Coelhos , Translocação Genética , Adulto Jovem
2.
Blood ; 122(9): 1599-609, 2013 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-23861246

RESUMO

Acute lymphoblastic leukemia (ALL) is currently treated with an intense regimen of chemotherapy yielding cure rates near 85%. However, alterations to treatment strategies using available drugs are unlikely to provide significant improvement in survival or decrease therapy-associated toxicities. Here, we report ectopic expression of the Mer receptor tyrosine kinase in pre-B-cell ALL (B-ALL) cell lines and pediatric patient samples. Inhibition of Mer in B-ALL cell lines decreased activation of AKT and MAPKs and led to transcriptional changes, including decreased expression of antiapoptotic PRKCB gene and increase in proapoptotic BAX and BBC3 genes. Further, Mer inhibition promoted chemosensitization, decreased colony-forming potential in clonogenic assays, and delayed disease onset in a mouse xenograft model of leukemia. Our results identify Mer as a potential therapeutic target in B-ALL and suggest that inhibitors of Mer may potentiate lymphoblast killing when used in combination with chemotherapy. This strategy could reduce minimal residual disease and/or allow for chemotherapy dose reduction, thereby leading to improved event-free survival and reduced therapy-associated toxicity for patients with B-ALL. Additionally, Mer is aberrantly expressed in numerous other malignancies suggesting that this approach may have broad applications.


Assuntos
Terapia de Alvo Molecular , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamento farmacológico , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Receptores Proteína Tirosina Quinases/antagonistas & inibidores , Animais , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , RNA Interferente Pequeno/farmacologia , RNA Interferente Pequeno/uso terapêutico , Ensaios Antitumorais Modelo de Xenoenxerto , c-Mer Tirosina Quinase
3.
Pediatr Dev Pathol ; 14(5): 402-6, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21491965

RESUMO

BCL2 and MYC are oncogenes often deregulated in lymphomas. Concurrent IGH-BCL2 and MYC translocations result in a highly aggressive behavior of these tumors. Both primary breast lymphoma and lymphoma with concurrent BCL2-IGH and MYC translocations are rare and are primarily seen in adult patients. As a result of limited clinician experience and the condition's rarity, it poses a great challenge to pediatric pathologists and oncologists in terms of making an accurate diagnosis and choosing better treatment regimens. In this article, we report a case of an adolescent patient who presented with high-grade breast lymphoma with concurrent BCL2-IGH and MYC-IGL translocations, and we review the clinical, pathological, and genetic features; management strategies; and outcomes associated with this unusual neoplasm.


Assuntos
Neoplasias da Mama/patologia , Genes de Cadeia Pesada de Imunoglobulina/genética , Genes de Cadeia Leve de Imunoglobulina/genética , Linfoma de Células B/patologia , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-myc/genética , Cariótipo Anormal , Neoplasias da Mama/genética , Neoplasias da Mama/terapia , Terapia Combinada , DNA de Neoplasias/análise , Evolução Fatal , Feminino , Regulação Neoplásica da Expressão Gênica , Rearranjo Gênico de Cadeia Pesada de Linfócito B/genética , Humanos , Linfoma de Células B/genética , Linfoma de Células B/terapia , Translocação Genética , Adulto Jovem
4.
Pediatr Dev Pathol ; 14(1): 57-63, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-20331368

RESUMO

Gray zone lymphomas are defined as lymphoid malignancies that cannot be reliably classified into a single distinct disease entity after all available morphologic, immunophenotypic, and molecular investigations have been performed. The 2008 World Health Organization Classification proposed 2 gray zone lesions: (1) B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma and (2) B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma. These gray zone lesions are rare, especially in pediatric patients, and create a great challenge to both pathologists and oncologists because this differential diagnosis has direct implications for management strategies. In this manuscript, we report 2 cases of pediatric patients with gray zone lymphoma and review clinicopathologic features, treatment options, and outcomes of this uncommon tumor.


Assuntos
Linfoma de Células B/patologia , Linfoma de Células B/fisiopatologia , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Humanos , Linfoma de Células B/terapia , Masculino
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