title: 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.
abstract: 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
authors: M
authors: Neumann
authors: S
authors: S
authors: Heesch
authors: N
authors: N
authors: Gökbuget
authors: S
authors: S
authors: Schwartz
authors: C
authors: C
authors: Schlee
authors: O
authors: O
authors: Benlasfer
authors: N
authors: N
authors: Farhadi-Sartangi
authors: J
authors: J
authors: Thibaut
authors: T
authors: T
authors: Burmeister
authors: D
authors: D
authors: Hoelzer
authors: W-K
authors: WK
authors: Hofmann
authors: E
authors: E
authors: Thiel
authors: C D
authors: CD
authors: Baldus