Hematopoiesis and leukemogenesis

The Hematopoiesis and leukemogenesis unit at IBCIT is involved in basic and translational research in leukemia. Major aim of our research activity is understanding the epigenetic mechanisms involved in transcription factors, chromatin remodeling activities and microRNAs that regulate the expression of genes directing hematopoietic stem cell differentiation/maturation and whose de-regulation leads to leukemia. Epigenetic modifications can be reversed by pharmacological treatment. Thus, the elucidation of these regulatory circuitries will contribute to the understanding of the molecular basis of cell differentiation and transformation, providing additional molecular targets for innovative therapeutic intervention in transplantation, stem cell expansion or molecular pathogenesis based “differentiation/transcriptional” strategies tailored at distinct leukemia subsets.

Unit members

Selected publications

Fazi,F., Zardo,G., Gelmetti,V., Travaglini,L., Ciolfi,A., Di Croce,L., Rosa,A., Bozzoni,I., Grignani,F., Lo-Coco,F., Pelicci,P.G., and Nervi,C. 2007. Heterochromatic gene repression of the retinoic acid pathway in acute myeloid leukemia. Blood 109, 4432-4440

Fazi,F., Racanicchi,S., Zardo,G., Starnes,L.M., Mancini,M., Travaglini,L., Diverio,D., Ammatuna,E., Cimino,G., Lo-Coco,F., Grignani,F., and Nervi,C. 2007. Epigenetic silencing of the myelopoiesis regulator microRNA-223 by the AML1/ETO oncoprotein. Cancer Cell 12: 457-466

Cimino,G, Lo-Coco,F, Fenu,S, Travaglini,L, Finolezzi,E, Mancini,M, Nanni,M, Careddu,A, Fazi,F, Padula,F, Fiorini,R, Aloe Spiriti,MA, Petti,MC, Venditti,A, Amadori,S, Mandelli,F, Pelicci,PG, and Nervi,C. 2006. Sequential Valproic acid/all-trans retinoic acid treatment reprograms differentiation in refractory and high-risk acute myeloid leukemia. Cancer Res. 66, 8903-8911

Fazi F, Rosa A, Fatica A, Gelmetti V, De Marchis ML, Nervi C, Bozzoni I. 2005. A mini-circuitry comprising microRNA-223 and transcription factors NFI-A and C/EBPα regulates human granulopoiesis. Cell 123, 819-31

De Felice L, Tatarelli C, Mascolo MG, Gregorj C, Agostini F, Fiorini R, Gelmetti V, Pascale S, Padula F, Petrucci MT, Arcese W, Nervi C: 2005.  Histone deacetylase inhibitor valproic acid enhances the cytokine-induced expansion of human hematopoietic stem cells. Cancer Res, 65: 1505-13