학술논문
RUNX1mutations in acute myeloid leukemia are associated with distinct clinico-pathologic and genetic features
Document Type
Article
Author
Gaidzik, V I; Teleanu, V; Papaemmanuil, E; Weber, D; Paschka, P; Hahn, J; Wallrabenstein, T; Kolbinger, B; Köhne, C H; Horst, H A; Brossart, P; Held, G; Kündgen, A; Ringhoffer, M; Götze, K; Rummel, M; Gerstung, M; Campbell, P; Kraus, J M; Kestler, H A; Thol, F; Heuser, M; Schlegelberger, B; Ganser, A; Bullinger, L; Schlenk, R F; Döhner, K; Döhner, H
Source
Leukemia; November 2016, Vol. 30 Issue: 11 p2160-2168, 9p
Subject
Language
ISSN
08876924; 14765551
Abstract
We evaluated the frequency, genetic architecture, clinico-pathologic features and prognostic impact of RUNX1mutations in 2439 adult patients with newly-diagnosed acute myeloid leukemia (AML). RUNX1mutations were found in 245 of 2439 (10%) patients; were almost mutually exclusive of AML with recurrent genetic abnormalities; and they co-occurred with a complex pattern of gene mutations, frequently involving mutations in epigenetic modifiers (ASXL1, IDH2, KMT2A,EZH2), components of the spliceosome complex (SRSF2, SF3B1) and STAG2, PHF6, BCOR. RUNX1mutations were associated with older age (16–59 years: 8.5%; ?60 years: 15.1%), male gender, more immature morphology and secondary AML evolving from myelodysplastic syndrome. In univariable analyses, RUNX1mutations were associated with inferior event-free (EFS, P<0.0001), relapse-free (RFS, P=0.0007) and overall survival (OS, P<0.0001) in all patients, remaining significant when age was considered. In multivariable analysis, RUNX1mutations predicted for inferior EFS (P=0.01). The effect of co-mutation varied by partner gene, where patients with the secondary genotypes RUNX1mut/ASXL1mut(OS, P=0.004), RUNX1mut/SRSF2mut(OS, P=0.007) and RUNX1mut/PHF6mut(OS, P=0.03) did significantly worse, whereas patients with the genotype RUNX1mut/IDH2mut(OS, P=0.04) had a better outcome. In conclusion, RUNX1-mutated AML is associated with a complex mutation cluster and is correlated with distinct clinico-pathologic features and inferior prognosis.