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

Tools

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., Schlenk, R.F., Gaidzik, V.I., Herzig, J.K., Aulitzky, T., Bullinger, L., Späth, D., Teleanu, V., Kündgen, A., Köhne, C.H., Brossart, P., Held, G., Horst, H.A., Ringhoffer, M., Götze, K., Nachbaur, D., Kindler, T., Heuser, M., Thol, F., Ganser, A., 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

Repository Staff Only: item control page