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

  • 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.

Download full text files

Export metadata

Additional Services

Share in Twitter Search Google Scholar
Metadaten
Author:Martin Neumann, Sandra Heesch, Nicola GökbugetGND, Stefan SchwartzORCiDGND, Cornelia Schlee, Ouidad Benlasfer, Nasrin Farhadi-Sartangi, Julia Thibaut, Thomas BurmeisterORCiDGND, Dieter HoelzerGND, Wolf-Karsten Hofmann, Eckhard Thiel, Claudia BaldusORCiDGND
URN:urn:nbn:de:hebis:30:3-244627
DOI:https://doi.org/10.1038/bcj.2011.49
ISSN:2044-5385
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/22829239
Parent Title (English):Blood cancer journal
Publisher:Nature Publishing Group
Place of publication:London [u.a.]
Document Type:Article
Language:English
Date of Publication (online):2012/01/27
Date of first Publication:2012/01/27
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2012/09/02
Tag:ETP-ALL; FLT3; NOTCH1; T-ALL; acute lymphoblastic leukemia; molecular characteristics
Volume:2
Issue:e55
Page Number:7
HeBIS-PPN:357293266
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung-Weitergabe unter gleichen Bedingungen