Bax, Bcl-2, and Bax/Bcl-2 as prognostic markers in acute myeloid leukemia: are we ready for Bcl-2-directed therapy?
Bax, Bcl-2, and Bax/Bcl-2 as prognostic markers in acute myeloid leukemia: are we ready for Bcl-2-directed therapy?
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DOI：
10.2147/cmar.s154608
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发表时间：
2018
影响因子：
3.3
通讯作者：
Hasnain SN
中科院分区：
文献类型：
--
作者：
Kulsoom B;Shamsi TS;Afsar NA;Memon Z;Ahmed N;Hasnain SN
许多抗癌药物在恶性细胞中诱导凋亡，并且对凋亡的抗性可能导致次优或无治疗益处。两种细胞质蛋白，B细胞淋巴瘤蛋白2（Bcl-2）-相关X（Bax）和Bcl-2，分别作为细胞凋亡的促进剂和抑制剂。Bax和Bcl-2及其比值已被认为是各种癌症的预后标志物。然而，报告了相互矛盾的结果。由于抗Bcl-2化疗的报道，对细胞凋亡的清晰理解也变得至关重要。探讨急性髓系白血病（AML）患者Bax和Bcl-2基因表达及其比值与疗效的关系。纳入了90例接受阿糖胞苷和柔红霉素治疗的AML患者的骨髓和/或血液样本。采用实时荧光定量聚合酶链反应（real-time polymerase chain reaction，RT-PCR）技术，采用ΔΔCt相对表达法检测Bax和Bcl-2的表达。骨髓和血液中Bax和Bcl-2的表达呈显著正相关（rs=0.5，p<0.01）。尽管与无应答者（中位数分别为0.66和0.24）相比，应答者（中位数分别为1.01和0.29）的Bax和Bcl-2骨髓表达倾向于保持较高水平，但差异未达到统计学显著性（U=784.5和733; p=0.68和0.28）。相反，Bax/Bcl-2比值在不良反应者中更高（中位数3.07 vs 1.78），尽管再次未能达到统计学显著性（U=698.5，p=0.07）。Bax和Bcl-2的表达在用阿糖胞苷和柔红霉素治疗的AML患者中在缓解、复发、耐药、总生存期和无病生存期方面没有显著差异，因此质疑新兴的抗Bcl-2治疗的效用。
Many anticancer drugs induce apoptosis in malignant cells, and resistance to apoptosis could lead to suboptimal or no therapeutic benefit. Two cytoplasmic proteins, B-cell lymphoma protein 2 (Bcl-2)-associated X (Bax) and Bcl-2, act as a promoter and an inhibitor of apoptosis, respectively. Both Bax and Bcl-2 as well as their ratio have been regarded as prognostic markers in various cancers. However, conflicting results have been reported. A clear understanding of apoptosis has also become crucial due to reports about anti-Bcl-2 chemotherapy. We explored the relationship of Bax and Bcl-2 gene expression and their ratio with the therapeutic response in acute myeloid leukemia (AML) patients. Bone marrow and/or blood samples from 90 AML patients treated with cytarabine and daunorubicin were included. Expression of Bax and Bcl-2 was determined through real-time polymerase chain reaction by using ΔΔCt method of relative expression. Bax and Bcl-2 expression among marrow and blood samples correlated with each other (rs=0.5, p<0.01). Although bone marrow expression of Bax and Bcl-2 tended to remain higher among responders (median 1.01 and 0.29, respectively) as compared to non-responders (median 0.66 and 0.24, respectively), the difference failed to reach statistical significance (U=784.5 and 733; p=0.68 and 0.28, respectively). Conversely, Bax/Bcl-2 ratio was higher among poor responders (median 3.07 vs 1.78), though again failed to reach statistical significance (U=698.5, p=0.07). Expression of Bax and Bcl-2 does not differ significantly among AML patients treated with cytarabine and daunorubicin in terms of remission, relapse, resistance, overall survival, and disease-free survival, thus questioning the utility of emerging anti-Bcl-2 therapy.