<i>BCL2</i> gene polymorphism could predict the treatment outcomes in acute myeloid leukemia patients

초록

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.

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