Clinical and molecular characterization of early T-cell precursor leukemia

• Verfasst von: Neumann, Martin [VerfasserIn]
• Verfasst von: Hofmann, Wolf-Karsten [VerfasserIn]
• Titel: Clinical and molecular characterization of early T-cell precursor leukemia
• Titelzusatz: a high-risk subgroup in adult T-ALL with a high frequency of FLT3 mutations
• Verf.angabe: 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
• Jahr: 2012
• Fussnoten: Published online 27 January 2012 ; Gesehen am 28.06.2018
• Titel Quelle: Enthalten in: Blood cancer journal
• Ort Quelle: [London] : Springer Nature, 2011
• Jahr Quelle: 2012
• Band/Heft Quelle: 2(2012,1) Artikel-Nummer e55, 7 Seiten
• ISSN Quelle: 2044-5385
• DOI: doi:10.1038/bcj.2011.49
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1576942147

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.