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Gene expression profiling identifies a subset of adult T-cell acute lymphoblastic leukemia (T-ALL) with myeloid-like gene features and overexpression of miR-223

Chiaretti, Sabina and Messina, Monica and Tavolaro, Simona and Zardo, Giuseppe and Elia, Loredana and Vitale, Antonella and Fatica, Alessandro Fatica and Gorello, Paolo and Piciocchi, Alfonso and Scappucci, Gina and Bozzoni, Irene and Fozza, Claudio and Candoni, Anna and Guarini, Anna and Foà, Robin (2010) Gene expression profiling identifies a subset of adult T-cell acute lymphoblastic leukemia (T-ALL) with myeloid-like gene features and overexpression of miR-223. Haematologica, Vol. 95 (7), p. 1114-1121. eISSN 1592-8721. Article.

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DOI: 10.3324/haematol.2009.015099

Abstract

Background. Until recently, few molecular aberrations were recognizedin acute lymphoblastic leukemia of T-cell origin (T-ALL); novel lesions have recently been identified and a certain degree of overlap between acute myeloid leukemia (AML) and T-ALL has been suggested. To identify novel T-ALL entities, gene expression profiling was performed and clinico-biologic features were studied. Design and methods. Sixty-nine untreated adult T-ALL cases were evaluated by oligonucleotide arrays: unsupervised and supervised analyses were performed. The upregulation of myeloid genes and miR-223 expression were validated by quantitative PCR. Results. By unsupervised clustering, we identified 5 subgroups. Of these, one branch included 7 patients whose gene expression profile resembled that of AML. These cases were characterized by the overexpression of a large set of myeloid-related genes as surface antigens, transcription factors and granule proteins. Q-PCR confirmed overexpression of MPO, CEBPA, CEBPB, GRN and IL-8. We thus evaluated the expression levels of miR-223, involved in myeloid differentiation: these cases had significantly higher levels of miR-223 than the other T-ALL, with values comparable to those observed in AML. Finally, these patients appear to have an unfavorable clinical course. Conclusions. By gene profiling we identified a subset of adult T-ALL, which represents 10% of the cases analyzed, that displays myeloid features. These cases were not recognized by standard approaches, underlining the importance of gene profiling in identifying novel acute leukemia subsets: the recognition of this subgroup may have clinical, prognostic and therapeutic implications.

Item Type:Article
ID Code:4422
Status:Published
Refereed:Yes
Uncontrolled Keywords:T-ALL, molecular aberrations, acute myeloid leukemia
Subjects:Area 06 - Scienze mediche > MED/15 Malattie del sangue
Divisions:001 Università di Sassari > 03 Istituti > Ematologia
Publisher:Fondazione Ferrata Storti
eISSN:1592-8721
Deposited On:31 Aug 2010 18:18

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