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Clinical and molecular characterization of early T-cell precursor leukemia: a high-risk subgroup in adult T-ALL with a high frequency of FLT3 mutations.
MedLine Citation:
PMID:  22829239     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
A subgroup of pediatric acute T-lymphoblastic leukemia (T-ALL) was characterized by a gene expression profile comparable to that of early T-cell precursors (ETPs) with a highly unfavorable outcome. We have investigated clinical and molecular characteristics of the ETP-ALL subgroup in adult T-ALL. As ETP-ALL represents a subgroup of early T-ALL we particularly focused on this cohort and identified 178 adult patients enrolled in the German Acute Lymphoblastic Leukemia Multicenter studies (05/93-07/03). Of these, 32% (57/178) were classified as ETP-ALL based on their characteristic immunophenotype. The outcome of adults with ETP-ALL was poor with an overall survival of only 35% at 10 years, comparable to the inferior outcome of early T-ALL with 38%. The molecular characterization of adult ETP-ALL revealed distinct alterations with overexpression of stem cell-related genes (BAALC, IGFBP7, MN1, WT1). Interestingly, we found a low rate of NOTCH1 mutations and no FBXW7 mutations in adult ETP-ALL. In contrast, FLT3 mutations, rare in the overall cohort of T-ALL, were very frequent and nearly exclusively found in ETP-ALL characterized by a specific immunophenotype. These molecular characteristics provide biologic insights and implications with respect to innovative treatment strategies (for example, tyrosine kinase inhibitors) for this high-risk subgroup of adult ETP-ALL.
Authors:
M Neumann; S Heesch; N Gökbuget; S Schwartz; C Schlee; O Benlasfer; N Farhadi-Sartangi; J Thibaut; T Burmeister; D Hoelzer; W-K Hofmann; E Thiel; C D Baldus
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Publication Detail:
Type:  Journal Article     Date:  2012-01-27
Journal Detail:
Title:  Blood cancer journal     Volume:  2     ISSN:  2044-5385     ISO Abbreviation:  Blood Cancer J     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-07-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101568469     Medline TA:  Blood Cancer J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e55     Citation Subset:  -    
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