Acquired mutations in ASXL1 in acute myeloid leukemia: prevalence and prognostic value

Acquired mutations in ASXL1 in acute myeloid leukemia: prevalence and prognostic value

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 de...

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Bibliographic Details
Published in:Haematologica (Roma) Vol. 97; no. 3; pp. 388 - 392
Main Authors: Pratcorona, M., Abbas, S., Sanders, M. A., Koenders, J. E., Kavelaars, F. G., Erpelinck-Verschueren, C. A. J., Zeilemakers, A., Lowenberg, B., Valk, P. J. M.
Format: Journal Article
Language:English
Published: Pavia Ferrata Storti Foundation 01-03-2012
Subjects:
Adolescent
Adult
Aged
Biological and medical sciences
Female
Hematologic and hematopoietic diseases
Humans
Leukemia, Myeloid, Acute - diagnosis
Leukemia, Myeloid, Acute - epidemiology
Leukemia, Myeloid, Acute - genetics
Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis
Male
Medical sciences
Middle Aged
Mutation
Original and Brief Reports
Prevalence
Prognosis
Repressor Proteins - genetics
Survival Analysis
Young Adult
Acute myelogenous leukemia
Prognosis
Prevalence
Hematology
acute myeloid leukemia
Acquired
ASXL1 mutations
Genetics
Malignant hemopathy
Mutation
Epidemiology
Cancer
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Summary: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.
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ISSN:0390-6078
1592-8721
DOI:10.3324/haematol.2011.051532