- Sabina Chiaretti1,
- Monica Messina1,
- Simona Tavolaro1,
- Giuseppe Zardo2,
- Loredana Elia1,
- Antonella Vitale1,
- Alessandro Fatica3,
- Paolo Gorello4,
- Alfonso Piciocchi5,
- Gina Scappucci6,
- Irene Bozzoni6,
- Claudio Fozza7,
- Anna Candoni8,
- Anna Guarini1 and
- Robin Foa'1,*
- 1 Div. of Hematology, Dept. of Cellular Biotechnologies, Sapienza University, Rome, Italy;
- 2 Division of Clinical Biochemistry, Sapienza University of Rome, Italy;
- 3 Division of Genetics and Molecular Biology, Sapienza, University of Rome, Italy;
- 4 Unit of Hematology and Bone Marrow Transplantation, University of Perugia, Italy;
- 5 GIMEMA Data Center, Rome, Italy;
- 6 Division of Genetics and Molecular Biology, Sapienza University of Rome, Italy;
- 7 Institute of Hematology, University of Sassari, Italy;
- 8 Clinica Ematologica, Policlinico Universitario, Udine, Italy
- ↵* Corresponding author; email:
Background. Until recently, few molecular aberrations were recognized in 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.
- Received July 30, 2009.
- Accepted January 7, 2010.
- Copyright © 2010, Ferrata Storti Foundation