ASXL1 mutations in younger adult patients with acute myeloid leukemia: A study by the German-Austrian acute myeloid leukemia study group

Peter Paschka, Richard F. Schlenk, Verena I. Gaidzik, Julia K. Herzig, Teresa Aulitzky, Lars Bullinger, Daniela Späth, Veronika Teleanu, Andrea Kündgen, Claus Henning Köhne, Peter Brossart, Gerhard Held, Heinz A. Horst, Mark Ringhoffer, Katharina Götze, David Nachbaur, Thomas Kindler, Michael Heuser, Felicitas Thol, Arnold GanserHartmut Döhner, Konstanze Döhner

Research output: Contribution to journalArticlepeer-review

85 Scopus citations

Abstract

We studied 1696 patients (18 to 61 years) with acute myeloid leukemia for ASXL1mutations and identified these mutations in 103 (6.1%) patients. ASXL1 mutations were associated with older age (P<0.0001), male sex (P=0.041), secondary acute myeloid leukemia (P<0.0001), and lower values for bone marrow (P<0.0001) and circulating (P<0.0001) blasts. ASXL1 mutations occurred in all cytogenetic risk-groups; normal karyotype (40%), other intermediate-risk cytogenetics (26%), high-risk (24%) and low-risk (10%) cytogenetics. ASXL1 mutations were associated with RUNX1(P<0.0001) and IDH2R140 mutations (P=0.007), whereas there was an inverse correlation with NPM1 (P<0.0001), FLT3-ITD (P=0.0002), and DNMT3A (P=0.02) mutations. Patients with ASXL1 mutations had a lower complete remission rate (56%versus 74%; P=0.0002), and both inferior event-free survival (at 5 years: 15.9%versus 29.0%; P=0.02) and overall survival (at 5 years: 30.3% versus 45.7%;P=0.0004) compared to patients with wildtype ASXL1. In multivariable analyses,ASXL1 and RUNX1 mutation as a single variable did not have a significant impact on prognosis. However, we observed a significant interaction (P=0.04) for these mutations, in that patients with the genotype ASXL1mutated/RUNX1mutated had a higher risk of death (hazard ratio 1.8) compared to patients without this genotype. ASXL1 mutation, particularly in the context of a coexisting RUNX1 mutation, constitutes a strong adverse prognostic factor in acute myeloid leukemia.

Original languageEnglish
Pages (from-to)324-330
Number of pages7
JournalHaematologica
Volume100
Issue number3
DOIs
StatePublished - 2015
Externally publishedYes

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