Apoptosis-related gene expression profile in chronic myeloid leukemia patients after imatinib mesylate and dasatinib therapy.
Acta Haematol
; 133(4): 354-364, 2015.
Article
em En
| MEDLINE
| ID: mdl-25721555
ABSTRACT
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.
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Base de dados:
MEDLINE
Assunto principal:
Piperazinas
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Pirimidinas
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Tiazóis
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Benzamidas
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Leucemia Mielogênica Crônica BCR-ABL Positiva
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Regulação Neoplásica da Expressão Gênica
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Inibidores de Proteínas Quinases
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article