Apoptosis-Related Gene Expression Profile in Chronic Myeloid Leukemia Patients after Imatinib Mesylate and Dasatinib Therapy

Autor(es)

Ferreira, Aline Fernanda ^[1] ; de Oliveira, Gislane L. V. ^[1] ; Tognon, Raquel ^[1] ; Collassanti, Maria Dulce S. ^[2] ; Zanichelli, Maria Aparecida ^[2] ; Hamerschlak, Nelson ^[3] ; de Souza, Ana Maria ^[1] ; Covas, Dimas Tadeu ^{[4, 5]} ; Kashima, Simone ^{[6, 5]} ; de Castro, Fabiola Attie ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Anal Clin Toxicol & Bromatol, BR-14040903 Ribeirao Preto, SP - Brazil

^[2] Inst Tratamento Canc Infantil ITACI, Sao Paulo - Brazil

^[3] Hosp Albert Einstein Sao Paulo, Soc Beneficente Israelita & Brasileira, Sao Paulo - Brazil

^[4] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Clin Med, BR-14040903 Ribeirao Preto, SP - Brazil

^[5] Inst Nacl Ciencia & Tecnol Celulas Tronco & Terap, INCTC, Ribeirao Preto - Brazil

^[6] Ctr Reg Hemoterapia Ribeirao Preto, Mol Biol Lab, Ribeirao Preto - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Acta Haematologica; v. 133, n. 4, p. 354-364, 2015.
• Citações Web of Science: 11

Resumo

Background/Aims: We investigated the effects of tyrosine kinase inhibitors (TKIs) on the expression of apoptosis-related genes (BCL-2 and death receptor family members) in chronic myeloid leukemia (CML) patients. Methods: Peripheral blood mononuclear cells from 32 healthy subjects and 26 CML patients were evaluated before and after treatment with imatinib mesylate (IM) and dasatinib (DAS) by quantitative PCR. Results: Anti-apoptotic genes (c-FLIP and MCL-1) were overexpressed and the pro-apoptotic BIK was reduced in CML patients. Expression of BMF, A1, c-FLIP, MCL-1, CIAP-2 and CIAP-1 was modulated by DAS. In IM-resistant patients, expression of A1, c-FLIP, CIAP-1 and MCL-1 was upregulated, and BCL-2, CIAP-2, BAK, BAX, BIK and FASL expression was downregulated. Conclusion: Taken together, our results point out that, in CML, DAS interferes with the apoptotic machinery regulation. In addition, the data suggest that apoptosis-related gene expression profiles are associated with primary resistance to IM. (C) 2015 S. Karger AG, Basel (AU)

• Processo FAPESP: 05/57746-8 - Efeito dos inibidores de tirosina-quinase na maquinaria apoptotica na leucemia mieloide cronica.
• Beneficiário: Aline Fernanda Ferreira
• Modalidade de apoio: Bolsas no Brasil - Mestrado