TY - JOUR
T1 - ASXL1 mutations in younger adult patients with acute myeloid leukemia
T2 - A study by the German-Austrian acute myeloid leukemia study group
AU - Paschka, Peter
AU - Schlenk, Richard F.
AU - Gaidzik, Verena I.
AU - Herzig, Julia K.
AU - Aulitzky, Teresa
AU - Bullinger, Lars
AU - Späth, Daniela
AU - Teleanu, Veronika
AU - Kündgen, Andrea
AU - Köhne, Claus Henning
AU - Brossart, Peter
AU - Held, Gerhard
AU - Horst, Heinz A.
AU - Ringhoffer, Mark
AU - Götze, Katharina
AU - Nachbaur, David
AU - Kindler, Thomas
AU - Heuser, Michael
AU - Thol, Felicitas
AU - Ganser, Arnold
AU - Döhner, Hartmut
AU - Döhner, Konstanze
N1 - Publisher Copyright:
© 2015 Ferrata Storti Foundation.
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/84924662543
U2 - 10.3324/haematol.2014.114157
DO - 10.3324/haematol.2014.114157
M3 - Article
C2 - 25596267
AN - SCOPUS:84924662543
SN - 0390-6078
VL - 100
SP - 324
EP - 330
JO - Haematologica
JF - Haematologica
IS - 3
ER -