title: Prognostic relevance of integrated genetic profiling in adult T-cell acute lymphoblastic leukemia.
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.
authors.affiliation: Institute for Cancer Genetics, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Pieter
authors.initials: P
authors.lastname: Van Vlierberghe
authors.forename: Alberto
authors.initials: A
authors.lastname: Ambesi-Impiombato
authors.forename: Kim
authors.initials: K
authors.lastname: De Keersmaecker
authors.forename: Michael
authors.initials: M
authors.lastname: Hadler
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Paietta
authors.forename: Martin S
authors.initials: MS
authors.lastname: Tallman
authors.forename: Jacob M
authors.initials: JM
authors.lastname: Rowe
authors.forename: Carles
authors.initials: C
authors.lastname: Forne
authors.forename: Montserrat
authors.initials: M
authors.lastname: Rue
authors.forename: Adolfo A
authors.initials: AA
authors.lastname: Ferrando
mesh_terms: D000328:Adult; D005260:Female; D018628:Gene Dosage / Q000235:genetics; D015973:Gene Expression Regulation, Leukemic; D023281:Genomics; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D046228:Microarray Analysis; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000378:metabolism / Q000401:mortality*; D011379:Prognosis; D012307:Risk Factors; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D008565:Membrane Proteins