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

Item Type:	Article
Title:	ASXL1 mutations in younger adult patients with acute myeloid leukemia: a study by the German-Austrian Acute Myeloid Leukemia Study Group
Creators Name:	Paschka, P. and Schlenk, R.F. and Gaidzik, V.I. and Herzig, J.K. and Aulitzky, T. and Bullinger, L. and Späth, D. and Teleanu, V. and Kündgen, A. and Köhne, C.H. and Brossart, P. and Held, G. and Horst, H.A. and Ringhoffer, M. and Götze, K. and Nachbaur, D. and Kindler, T. and Heuser, M. and Thol, F. and Ganser, A. and Döhner, H. and Döhner, K.
Abstract:	We studied 1696 patients (18 to 61 years) with acute myeloid leukemia for ASXL1 mutations 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 IDH2(R140) 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 ASXL1(mutated)/RUNX1(mutated) 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.
Keywords:	Acute Myeloid Leukemia, Age Factors, Antineoplastic Agents, Bone Marrow, Core Binding Factor Alpha 2 Subunit, DNA (Cytosine-5-)-Methyltransferases, DNA Methyltransferase 3A, Isocitrate Dehydrogenase, Karyotype, Nuclear Proteins, Nucleophosmin, Prognosis, Prospective Studies, Repressor Proteins, Sex Factors, Survival Analysis, fms-Like Tyrosine Kinase 3
Source:	Haematologica
ISSN:	0390-6078
Publisher:	Ferrata Storti Foundation
Volume:	100
Number:	3
Page Range:	324-330
Date:	March 2015
Additional Information:	Copyright © 2015 Ferrata Storti Foundation. This is an open-access paper.
Official Publication:	https://doi.org/10.3324/haematol.2014.114157
External Fulltext:	View full text on PubMed Central
PubMed:	View item in PubMed

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