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 M. Paietta, Martin S. Tallman, Jacob M. Rowe, Carles Forne, Montserrat Rue, Adolfo A. Ferrando

Research output: Contribution to journalArticle

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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 and mature 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 - Jul 4 2013

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Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
T-cells
Gene expression
Tumors
Genes
Oncology
Microarrays
Chromosomes
Transcriptome
Mutation
Chromosomes, Human, Pair 17
Sequence Deletion
Tumor Suppressor Genes
Clinical Trials
Survival
Neoplasms

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Van Vlierberghe, P., Ambesi-Impiombato, A., De Keersmaecker, K., Hadler, M., Paietta, E. M., Tallman, M. S., ... 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

Prognostic relevance of integrated genetic profiling in adult T-cell acute lymphoblastic leukemia. / Van Vlierberghe, Pieter; Ambesi-Impiombato, Alberto; De Keersmaecker, Kim; Hadler, Michael; Paietta, Elisabeth M.; Tallman, Martin S.; Rowe, Jacob M.; Forne, Carles; Rue, Montserrat; Ferrando, Adolfo A.

In: Blood, Vol. 122, No. 1, 04.07.2013, p. 74-82.

Research output: Contribution to journalArticle

Van Vlierberghe, P, Ambesi-Impiombato, A, De Keersmaecker, K, Hadler, M, Paietta, EM, Tallman, MS, Rowe, JM, Forne, C, Rue, M & Ferrando, AA 2013, 'Prognostic relevance of integrated genetic profiling in adult T-cell acute lymphoblastic leukemia.', Blood, vol. 122, no. 1, pp. 74-82. https://doi.org/10.1182/blood-2013-03-491092
Van Vlierberghe P, Ambesi-Impiombato A, De Keersmaecker K, Hadler M, Paietta EM, Tallman MS et al. Prognostic relevance of integrated genetic profiling in adult T-cell acute lymphoblastic leukemia. Blood. 2013 Jul 4;122(1):74-82. https://doi.org/10.1182/blood-2013-03-491092
Van Vlierberghe, Pieter ; Ambesi-Impiombato, Alberto ; De Keersmaecker, Kim ; Hadler, Michael ; Paietta, Elisabeth M. ; Tallman, Martin S. ; Rowe, Jacob M. ; Forne, Carles ; Rue, Montserrat ; Ferrando, Adolfo A. / Prognostic relevance of integrated genetic profiling in adult T-cell acute lymphoblastic leukemia. In: Blood. 2013 ; Vol. 122, No. 1. pp. 74-82.
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