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Blood. 2013 Jul 4;122(1):74-82. doi: 10.1182/blood-2013-03-491092. Epub 2013 May 17.

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

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1
Institute for Cancer Genetics, Columbia University Medical Center, New York, NY 10032, USA.

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.

PMID:
23687089
PMCID:
PMC3701905
DOI:
10.1182/blood-2013-03-491092
[Indexed for MEDLINE]
Free PMC Article
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