title: BCL2 gene polymorphism could predict the treatment outcomes in acute myeloid leukemia patients.
abstract: 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.
authors.affiliation: Department of Hematology/Oncology, Kyungpook National University Hospital, Daegu, Republic of Korea.
authors.forename: Joon Ho
authors.initials: JH
authors.lastname: Moon
authors.forename: Sang Kyun
authors.initials: SK
authors.lastname: Sohn
authors.forename: Myung-Hoon
authors.initials: MH
authors.lastname: Lee
authors.forename: Jun Ho
authors.initials: JH
authors.lastname: Jang
authors.forename: Kihyun
authors.initials: K
authors.lastname: Kim
authors.forename: Chul Won
authors.initials: CW
authors.lastname: Jung
authors.forename: Dong Hwan
authors.initials: DH
authors.lastname: Kim
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D019254:Genes, bcl-2 / Q000235:genetics*; D005838:Genotype; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents