Prognostic relevance of integrated genetic profiling in adult T-cell acute lymphoblastic leukemia

Pieter Van Vlierberghe, Alberto Ambesi-Impiombato, Kim De Keersmaecker, Michael Hadler, Elisabeth Paietta, Martin S. Tallman, Jacob M. Rowe, Carles Forne, Montserrat Rue, Adolfo A. Ferrando

Research output: Contribution to journalArticle

78 Scopus citations

Abstract

Adult T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic tumor associated with poor outcome. In this study, we analyzed the prognostic relevance of genetic alterations, immunophenotypic markers, and microarray gene expression signatures in a panel of 53 adult T-ALL patients treated in the Eastern Cooperative Oncology Group E2993 clinical trial. An early immature gene expression signature, the absence of bi-allelic TCRG deletion, CD13 surface expression, heterozygous deletions of the short arm of chromosome 17, and mutations in IDH1/IDH2 and DNMT3A genes are associated with poor prognosis in this series. In contrast, expression of CD8 or CD62L, homozygous deletion of CDKN2A/CDKN2B, NOTCH1 and/or FBXW7 mutations, and mutations or deletions in the BCL11B tumor suppressor gene were associated with improved overall survival. Importantly, the prognostic relevance of CD13 expression and homozygous CDKN2A/CDKN2B deletions was restricted to cortical andmature T-ALLs. Conversely, mutations in IDH1/IDH2 and DNMT3A were specifically associated with poor outcome in early immature adult T-ALLs. This trial was registered at www.clinicaltrials.gov as #NCT00002514.

Original languageEnglish (US)
Pages (from-to)74-82
Number of pages9
JournalBlood
Volume122
Issue number1
DOIs
StatePublished - Jan 1 2013

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Van Vlierberghe, P., Ambesi-Impiombato, A., De Keersmaecker, K., Hadler, M., Paietta, E., Tallman, M. S., Rowe, J. M., Forne, C., Rue, M., & Ferrando, A. A. (2013). Prognostic relevance of integrated genetic profiling in adult T-cell acute lymphoblastic leukemia. Blood, 122(1), 74-82. https://doi.org/10.1182/blood-2013-03-491092