Acta haematologica · 2015
Apoptosis-related gene expression profile in chronic myeloid leukemia patients after imatinib mesylate and dasatinib therapy.
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Ferreira Aline Fernanda, de Oliveira Gislane L V, Tognon Raquel, Collassanti Maria Dulce S, Zanichelli Maria Aparecida, Hamerschlak Nelson, de Souza Ana Maria, Covas Dimas Tadeu, Kashima Simone, de Castro Fabiola Attie
Аннотация
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.
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.
Предметные рубрики MeSH
AdultAgedAntineoplastic AgentsApoptosis Regulatory ProteinsBenzamidesCASP8 and FADD-Like Apoptosis Regulating ProteinDasatinibDrug Resistance, NeoplasmDrug Therapy, CombinationFusion Proteins, bcr-ablGene Expression Regulation, NeoplasticHumansImatinib MesylateLeukemia, Myelogenous, Chronic, BCR-ABL PositiveLeukocytes, MononuclearMaleMiddle AgedPiperazinesProtein Kinase InhibitorsPyrimidinesRNA, MessengerThiazolesTranscriptome