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The molecular profile of adult T-cell acute lymphoblastic leukemia: Mutations in RUNX1 and DNMT3A are associated with poor prognosis in T-ALL.
MedLine Citation:
PMID:  23341344     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive and heterogeneous disease. The diagnosis is predominantly based on immunophenotyping. In addition to known cytogenetic abnormalities molecular mutations were recently identified. Here, 90 adult T-ALL cases were investigated for mutations in NOTCH1, FBXW7, PHF6, CDKN2A, DNMT3A, FLT3, PTEN, and RUNX1 using 454 next-generation amplicon sequencing and melting curve analyses. These data were further complemented by FISH, chromosome banding, array CGH, and CDKN2B promoter methylation analyses. NOTCH1 was the most frequently mutated gene with a 71.1% frequency followed by FBXW7 (18.9%), PHF6 (39.5%), DNMT3A (17.8%), RUNX1 (15.5%), PTEN (10.0%), CDKN2A (4.4%), FLT3-ITD (2.2%), and FLT3-TKD (1.1%). In total, 84/90 (93.3%) cases harbored at least one mutation. Combining these data with CDKN2A/B deletions and CDKN2B methylation status, we detected minimum one aberration in 89/90 (98.9%) patients. Survival analyses revealed the subtype as defined by the immunophenotype as the strongest independent prognostic factor. When restricting the survival analysis to the early T-ALL subtype, a strong association of RUNX1 (P = 0.027) and DNMT3A (P = 0.005) mutations with shorter overall survival was observed. In conclusion, RUNX1 and DNMT3A are frequently mutated in T-ALL and are associated with poor prognosis in early T-ALL. © 2013 Wiley Periodicals, Inc.
Authors:
Vera Grossmann; Claudia Haferlach; Sandra Weissmann; Andreas Roller; Sonja Schindela; Franziska Poetzinger; Kathrin Stadler; Frauke Bellos; Wolfgang Kern; Torsten Haferlach; Susanne Schnittger; Alexander Kohlmann
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-23
Journal Detail:
Title:  Genes, chromosomes & cancer     Volume:  -     ISSN:  1098-2264     ISO Abbreviation:  Genes Chromosomes Cancer     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-23     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9007329     Medline TA:  Genes Chromosomes Cancer     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2013 Wiley Periodicals, Inc.
Affiliation:
MLL Munich Leukemia Laboratory, Max-Lebsche-Platz 31, 81377 Munich, Germany. vera.grossmann@mll.com.
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