ASXL1 mutations in younger adult patients with acute myeloid leukemia: a study by the German-Austrian Acute Myeloid Leukemia Study Group

作者：Paschka Peter; Schlenk Richard F; Gaidzik Verena I; Herzig Julia K; Aulitzky Teresa; Bullinger Lars; Spaeth Daniela; Teleanu Veronika; Kuendgen Andrea; Koehne Claus Henning; Brossart Peter; Held Gerhard; Horst Heinz A; Ringhoffer Mark; Goetze Katharina; Nachbaur David; Kindler Thomas; Heuser Michael; Thol Felicitas; Ganser Arnold; Doehner Hartmut; Doehner Konstanze

来源：Haematologica-The Hematology Journal, 2015, 100(3): 324-330.

DOI：10.3324/haematol.2014.114157

We studied 1696 patients (18 to 61 years) with acute myeloid leukemia for ASXL1 mutations and identified these mutations in 103 (6.1%) patients. ASXL1mutations 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.

• 出版日期2015-3