Apoptosis-Related Gene Expression Profile in Chronic Myeloid Leukemia Patients after Imatinib Mesylate and Dasatinib Therapy
Apoptosis-Related Gene Expression Profile in Chronic Myeloid Leukemia Patients after Imatinib Mesylate and Dasatinib Therapy
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DOI：
10.1159/000369446
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发表时间：
2015-01-01
影响因子：
2.4
通讯作者：
de Castro, Fabiola Attie
中科院分区：
文献类型：
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作者：
Ferreira, Aline Fernanda;de Oliveira, Gislane L. V.;de Castro, Fabiola Attie
背景/目的：我们研究了酪氨酸激酶抑制剂 (TKI) 对慢性粒细胞白血病 (CML) 患者凋亡相关基因（BCL-2 和死亡受体家族成员）表达的影响。方法：采用定量 PCR 方法对 32 名健康受试者和 26 名 CML 患者接受甲磺酸伊马替尼 (IM) 和达沙替尼 (DAS) 治疗前后的外周血单核细胞进行评估。结果：CML 患者抗凋亡基因（c-FLIP 和 MCL-1）过表达，促凋亡 BIK 降低。 BMF、A1、c-FLIP、MCL-1、CIAP-2 和 CIAP-1 的表达受 DAS 调节。 IM耐药患者中，A1、c-FLIP、CIAP-1和MCL-1表达上调，BCL-2、CIAP-2、BAK、BAX、BIK和FASL表达下调。结论：综上所述，我们的结果表明，在 CML 中，DAS 干扰细胞凋亡机制的调节。此外，数据表明细胞凋亡相关基因表达谱与 IM 的原发性耐药相关。 (C) 2015 S. Karger AG，巴塞尔
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