AML1/RUNX1 mutations in 470 adult patients with de novo acute myeloid leukemia: prognostic implication and interaction with other gene alterations.
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.
Tang
Jih-Luh
JL
Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Hou
Hsin-An
HA
Chen
Chien-Yuan
CY
Liu
Chieh-Yu
CY
Chou
Wen-Chien
WC
Tseng
Mei-Hsuan
MH
Huang
Chi-Fei
CF
Lee
Fen-Yu
FY
Liu
Ming-Chih
MC
Yao
Ming
M
Huang
Shang-Yi
SY
Ko
Bor-Sheng
BS
Hsu
Szu-Chun
SC
Wu
Shang-Ju
SJ
Tsay
Woei
W
Chen
Yao-Chang
YC
Lin
Liang-In
LI
Tien
Hwei-Fang
HF
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
D050676:Core Binding Factor Alpha 2 Subunit; C000716967:NPM1 protein, human; D000090243:Nucleophosmin