BCL2 gene polymorphism could predict the treatment outcomes in acute myeloid leukemia patients
BCL2 gene polymorphism could predict the treatment outcomes in acute myeloid leukemia patients
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DOI：
10.1016/j.leukres.2009.05.009
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发表时间：
2010-02-01
影响因子：
2.7
通讯作者：
Kim, Dong Hwan
中科院分区：
文献类型：
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作者：
Moon, Joon Ho;Sohn, Sang Kyun;Kim, Dong Hwan
Bcl-2蛋白抑制由多种伤害性刺激诱导的造血干细胞凋亡（程序性细胞死亡），从而介导化学抗性并降低化学敏感性。高Bcl-2表达与急性髓细胞白血病（AML）治疗后的不良结局相关。目前的研究确定了BCL 2基因单核苷酸多态性（SNP）是否会影响99例AML患者（不包括急性早幼粒细胞白血病）的治疗结果。检测了两种基因型，包括BCL 2-938 C>A（rs 2279115）和+21 A>G（rs 1801018）。无论是-938 C>A还是+21 A>G BLC 2基因型都与化疗后的完全缓解（CR）率无关。-938 A>C BCL 2基因型不影响无白血病生存期（LFS）、无事件生存期（EFS）或总生存期（OS）。然而，有趣的是，BCL 2 + 21 A>G基因型与LFS、EFS和OS相关：具有+21 AA基因型的组具有显著更长的中值LFS（p < 0.001）或EFS（p = 0.004）和OS（p = 0.04）。多变量分析证实，BCL 2基因SNP是LFS的独立预后因素（p = 0.05，HR 1.83，95% C.I. [1.02-3.45]）和EFS（p = 0.02，HR 3.13 [1.34-6.43]），但不适用于OS（p = 0.1）。这些数据表明，Bcl-2介导的机制参与了AML化疗耐药性的发展。(C)2009爱思唯尔有限公司版权所有。
The Bcl-2 protein inhibits apoptosis (programmed cell death) of hematopoietic stem cells induced by a variety of noxious stimuli, thus mediating chemoresistance and decreasing chemosensitivity. Higher Bcl-2 expression correlates to an adverse outcome following therapy for acute myeloid leukemia (AML). The current study determined whether a BCL2 gene single nucleotide polymorphism (SNP) could affect treatment outcomes in 99 AML patients excluding acute promyelocytic leukemia. Two genotypes were tested, including BCL2 -938 C>A (rs2279115) and +21 A>G (rs1801018). Neither the -938 C>A nor the +21 A>G BLC2 genotype was associated with complete remission (CR) rates following chemotherapy. The -938 A>C BCL2 genotype did not affect leukemia-free survival (LFS), event-free survival (EFS) or overall survival (OS). However, of interest, the BCL2 +21 A>G genotype correlated with LFS, EFS and OS: The group with the +21 AA genotype had a significantly longer median LFS (p < 0.001) or EFS (p = 0.004), and OS (p = 0.04). The multivariate analyses confirmed that this BCL2 gene SNP is an independent prognostic factor for LFS (p = 0.05, HR 1.83, 95% C.I. [1.02-3.45]) and EFS (p = 0.02, HR 3.13 [1.34-6.43]), but not for OS (p = 0.1). This data suggests the involvement of a Bcl-2-mediated mechanism in the development of chemoresistance in AML. (C) 2009 Elsevier Ltd. All rights reserved.