title: Acquired mutations in ASXL1 in acute myeloid leukemia: prevalence and prognostic value.
abstract: Somatic mutations in the additional sex comb-like 1 (ASXL1) gene have been described in various types of myeloid malignancies, including acute myeloid leukemia. Analysis of novel markers, such as ASXL1 mutations, in independent clinical trials is indispensable before considering them for clinical decision-making. We analyzed 882 well-characterized acute myeloid leukemia cases to determine the prevalence and prognostic impact of ASXL1 exon12 mutations. Truncating ASXL1 mutations were present in 46 cases (5.3%). ASXL1 mutations were inversely associated with FLT3 internal tandem duplications and mutually exclusive with NPM1 mutations. ASXL1 mutations were an unfavorable prognostic factor as regards survival (median overall survival 15.9 months vs. 22.3 months; P=0.019), with a significantly lower complete response rate (61% vs. 79.6%; P=0.004). In multivariate analyses, ASXL1 mutations were independently associated with inferior poor overall survival (HR 1.52, P=0.032). In conclusion, ASXL1 mutations are common mutations in acute myeloid leukemia and indicate a poor therapy outcome.
authors: Department of Hematology, IDIBAPS, Hospital Clínic de Barcelona, Barcelona, Spain.
authors: Marta
authors: M
authors: Pratcorona
authors: Saman
authors: S
authors: Abbas
authors: Mathijs A
authors: MA
authors: Sanders
authors: Jasper E
authors: JE
authors: Koenders
authors: François G
authors: FG
authors: Kavelaars
authors: Claudia A J
authors: CA
authors: Erpelinck-Verschueren
authors: Annelieke
authors: A
authors: Zeilemakers
authors: Bob
authors: B
authors: Löwenberg
authors: Peter J M
authors: PJ
authors: Valk
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D000090243:Nucleophosmin; D015995:Prevalence; D011379:Prognosis; D012097:Repressor Proteins / Q000235:genetics*; D016019:Survival Analysis; D055815:Young Adult
chemical_list: C473949:ASXL1 protein, human; C000716967:NPM1 protein, human; D012097:Repressor Proteins; D000090243:Nucleophosmin