Polymorphisms in Myeloid Cell Leukemia-1 and the Risk for Acute Myeloid Leukemia

The essential pathogenic mechanism in acute myeloid leukemia (AML) is a heterogeneous group of malignant diseases arising as the result of progressive genetic damage occurring in hemopoietic progenitor cells. Mcl-1 (myeloid cell leukemia-1), an antiapoptotic protein of the Bcl-2 family, is located on chromosome 1 and has three exons and two introns. Overexpression of Mcl-1 delays apoptosis induced by cytotoxic agents, c-myc overexpression, and growth factor withdrawal in hematopoietuc cells. To evaluate the association between genetic variants of Mcl-1 gene and risk of AML, we genotyped two polymorphisms in promoter of Mcl-1[rs3738484; −324 C>A and rs3831987; −284 insertion(6bp or18bp)/deletion]. A case-control study of 728 controls and 660 cases was conducted in Chonnam National University Hwasun Hospital, Korea. The Mcl −324 CA and combined CA/AA genotype was significantly associated with a decreased risk for AML [odds ratio (OR) _CA = 0.75; 95% confidence interval (CI) = 0.60–0.95; OR_CA/AA = 0.76; 95% CI = 0.61–0.96]. There was no association with the Mcl -284 insertion/deletion and AML. The haplotype A-ins18bp is significantly associated with the risk of AML. Using subjects with the haplotype A- del, the OR of haplotype A-ins18bp is 5.87 (95% CI 1.7–20.06 p= 0.006). Our results suggest that antiapoptotic protein, Mcl-1 polymorphism may influence susceptibility to AML.