AML1/RUNX1 Mutations in 470 Adult Patients with De Novo Acute Myeloid Leukemia: Prognostic Implication and Interaction with Other Gene Alterations.

Abstract 1564

Poster Board I-587

Somatic mutation of AML1/RUNX1 (RUNX1) gene is seen in acute myeloid leukemia (AML) M0 subtype and 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 individuals (13.2%); 32 were in N-terminal and 31, C-terminal. The RUNX1 mutation was closely associated with male gender, older age, lower LDH value, FAB 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 (P=0.0061), but negatively associated with CEBPA (P=0.0057) and NPM1 mutations (P=0.0001). AML patients with RUNX1 mutations had a significantly lower complete remission rate, shorter disease-free and overall survival than those without the mutation (P=0.0087, P<0.0001 and P=0.012, respectively). Subgroup analysis of patients with normal karyotype showed that RUNX1-mutation was also closely associated with worse OS and DFS (P= 0.001 and P=0.001, respectively). Multivariate analysis demonstrated that RUNX1 mutation was an independent poor prognostic factor for overall survival (hazard ratio 1.874, 95% CI, 1.101- 3.189, P=0.021). Sequential analysis in 133 patients revealed that none acquired novel RUNX1 mutations during clinical courses. Our findings provide evidences that RUNX1 mutations are associated with distinct biological and clinical characteristics and poor prognosis in patients with de novo AML.