title: Identification and functional analysis of acute myeloid leukemia susceptibility associated single nucleotide polymorphisms at non-protein coding regions of RUNX1.
abstract: Little is known about the susceptibility to acute myeloid leukemia. We aim to search non-protein coding regions of key hematopoiesis transcription factors for genetic variations associated with acute myeloid leukemia susceptibility. We genotyped SNPs of RUNX1 P1 promoter, P2 promoter, +23 enhancer, intron 5.2 enhancer, PU.1 promoter, CEBPA promoter, and CEBPE promoter from acute myeloid leukemia patients and healthy controls. Rs2249650 and rs2268276 at RUNX1 intron 5.2 enhancer were found to be associated with acute myeloid leukemia susceptibility. Artificial reporters containing different rs2249650 and rs2268276 alleles showed differential activities in the K562 cell line, a human immortalized myeloid leukemia line. Rs2249650 contributes to reporter activities more than rs2268276. Gel shift assay is consistent with the luciferase assay. Supershift assay indicated that one potential binding protein was PU.1. To sum up, rs2268276 and especially rs2249650 may be qualified as new acute myeloid leukemia susceptibility-associated SNPs.
authors.affiliation: a Laboratory for Stem Cell and Regenerative Medicine .
authors.forename: Xin
authors.initials: X
authors.lastname: Xu
authors.affiliation: b Department of Obstetrics .
authors.forename: Xiuyu
authors.initials: X
authors.lastname: Ren
authors.affiliation: c Department of Hematology , and.
authors.forename: Haiying
authors.initials: H
authors.lastname: Wang
authors.affiliation: a Laboratory for Stem Cell and Regenerative Medicine .
authors.forename: Yao
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: d Department of Laboratory Medicine , The Affiliated Hospital of Weifang Medical University , Weifang , Shandong Province , PR China .
authors.forename: Zhengjun
authors.initials: Z
authors.lastname: Yi
authors.affiliation: e The People's Hospital of Zhangqiu , Jinan , Shandong Province , PR China .
authors.forename: Kaifeng
authors.initials: K
authors.lastname: Wang
authors.affiliation: f Department of Medical Imaging , The Affiliated Hospital of Weifang Medical University , Weifang , Shandong Province , PR China .
authors.forename: Shizhuang
authors.initials: S
authors.lastname: Zhang
authors.affiliation: g Weifang University , Weifang , Shandong Province , PR China , and.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: h Department of Biochemistry & Molecular Biology , University of Louisville School of Medicine , Louisville , KY , USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Samuelson
authors.affiliation: a Laboratory for Stem Cell and Regenerative Medicine .
authors.forename: Zhenbo
authors.initials: Z
authors.lastname: Hu
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D001483:Base Sequence; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D020506:Untranslated Regions
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D020506:Untranslated Regions
keywords: Acute myeloid leukemia susceptibility; RUNX1; rs2249650; rs2268276