title: ASXL1 mutations are infrequent in young patients with primary acute myeloid leukemia and their detection has a limited role in therapeutic risk stratification.
abstract: ASXL1 mutations are recurrent in acute myeloid leukemia (AML), but it is unclear whether ASXL1 genotype might influence patient management. We analyzed frequency and impact in younger (15-59 years) and older (≥ 60 years) patients with primary or secondary disease. Overall, 9% had truncating mutations. Incidence was significantly lower in younger patients with primary than with secondary disease (4%, 12%; p = 0.03). In older patients it did not differ significantly (11%, 15%; p = 0.5). In univariate analysis, ASXL1-mutated patients had a worse outcome (5-year relapse 83% vs. 56%, p = 0.01; overall survival [OS] 6% vs. 22%, p = 0.02). However in multivariate analysis, ASXL1 mutations had no prognostic significance (for OS, p = 0.3), because age was a major confounding factor. The low incidence of mutations in younger patients with primary disease and the lack of significance in multivariate analysis indicate that there is a limited role for screening at diagnosis for ASXL1 mutations for the purpose of prognostic stratification.
authors: Department of Haematology, UCL Cancer Institute , London , UK.
authors: Dima
authors: D
authors: El-Sharkawi
authors: Akbar
authors: A
authors: Ali
authors: Catherine M
authors: CM
authors: Evans
authors: Robert K
authors: RK
authors: Hills
authors: Alan K
authors: AK
authors: Burnett
authors: David C
authors: DC
authors: Linch
authors: Rosemary E
authors: RE
authors: Gale
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D004252:DNA Mutational Analysis; D005260:Female; D005838:Genotype; D006801:Humans; D015994:Incidence; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009154:Mutation; D063868:Patient Outcome Assessment; D011379:Prognosis; D012097:Repressor Proteins / Q000235:genetics*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C473949:ASXL1 protein, human; D015415:Biomarkers; D012097:Repressor Proteins
keywords: ASXL1; Acute myeloid leukemia; mutation; prognostic significance