title: AML1/RUNX1 mutations in 470 adult patients with de novo acute myeloid leukemia: prognostic implication and interaction with other gene alterations.
abstract: Somatic mutation of the AML1/RUNX1(RUNX1) gene is seen in acute myeloid leukemia (AML) M0 subtype and in AML transformed from myelodysplastic syndrome, but the impact of this gene mutation on survival in AML patients remains unclear. In this study, we sought to determine the clinical implications of RUNX1 mutations in 470 adult patients with de novo non-M3 AML. Sixty-three distinct RUNX1 mutations were identified in 62 persons (13.2%); 32 were in N-terminal and 31, C-terminal. The RUNX1 mutation was closely associated with male sex, older age, lower lactic dehydrogenase value, French-American-British M0/M1 subtypes, and expression of HLA-DR and CD34, but inversely correlated with CD33, CD15, CD19, and CD56 expression. Furthermore, the mutation was positively associated with MLL/PTD but negatively associated with CEBPA and NPM1 mutations. AML patients with RUNX1 mutations had a significantly lower complete remission rate and shorter disease-free and overall survival than those without the mutation. Multivariate analysis demonstrated that RUNX1 mutation was an independent poor prognostic factor for overall survival. Sequential analysis in 133 patients revealed that none acquired novel RUNX1 mutations during clinical courses. Our findings provide evidence that RUNX1 mutations are associated with distinct biologic and clinical characteristics and poor prognosis in patients with de novo AML.
authors.affiliation: Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Jih-Luh
authors.initials: JL
authors.lastname: Tang
authors.forename: Hsin-An
authors.initials: HA
authors.lastname: Hou
authors.forename: Chien-Yuan
authors.initials: CY
authors.lastname: Chen
authors.forename: Chieh-Yu
authors.initials: CY
authors.lastname: Liu
authors.forename: Wen-Chien
authors.initials: WC
authors.lastname: Chou
authors.forename: Mei-Hsuan
authors.initials: MH
authors.lastname: Tseng
authors.forename: Chi-Fei
authors.initials: CF
authors.lastname: Huang
authors.forename: Fen-Yu
authors.initials: FY
authors.lastname: Lee
authors.forename: Ming-Chih
authors.initials: MC
authors.lastname: Liu
authors.forename: Ming
authors.initials: M
authors.lastname: Yao
authors.forename: Shang-Yi
authors.initials: SY
authors.lastname: Huang
authors.forename: Bor-Sheng
authors.initials: BS
authors.lastname: Ko
authors.forename: Szu-Chun
authors.initials: SC
authors.lastname: Hsu
authors.forename: Shang-Ju
authors.initials: SJ
authors.lastname: Wu
authors.forename: Woei
authors.initials: W
authors.lastname: Tsay
authors.forename: Yao-Chang
authors.initials: YC
authors.lastname: Chen
authors.forename: Liang-In
authors.initials: LI
authors.lastname: Lin
authors.forename: Hwei-Fang
authors.initials: HF
authors.lastname: Tien
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics*; D004252:DNA Mutational Analysis; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D000090243:Nucleophosmin; D011379:Prognosis; D012307:Risk Factors; D012737:Sex Factors
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; C000716967:NPM1 protein, human; D000090243:Nucleophosmin