Epigenetic changes are common alterations in cancer cells. Here, we have investigated the role of Polycomb group proteins in the establishment and maintenance of the aberrant silencing of tumor suppressor genes during transformation induced by the leukemia-associated PML-RARα fusion protein. We show that in leukemic cells knockdown of SUZ12, a key component of Polycomb repressive complex 2 (PRC2), reverts not only histone modification but also induces DNA demethylation of PML-RARα target genes. This results in promoter reactivation and granulocytic differentiation. Importantly, the epigenetic alterations caused by PML-RARα can be reverted by retinoic acid treatment of primary blasts from leukemic patients. Our results demonstrate that the direct targeting of Polycomb group proteins by an oncogene plays a key role during carcinogenesis.

Role of the polycomb repressive complex 2 in acute promyelocytic leukemia / R. Villa, D. Pasini, A. Gutierrez, L. Morey, M. Occhionorelli, E. Vire, J.F. Nomdedeu, T. Jenuwein, P.G. Pelicci, S. Minucci, F. Fuks, K. Helin, L. Di Croce. - In: CANCER CELL. - ISSN 1535-6108. - 11:6(2007 Jun), pp. 513-525.

Role of the polycomb repressive complex 2 in acute promyelocytic leukemia

D. Pasini;P.G. Pelicci;S. Minucci;
2007

Abstract

Epigenetic changes are common alterations in cancer cells. Here, we have investigated the role of Polycomb group proteins in the establishment and maintenance of the aberrant silencing of tumor suppressor genes during transformation induced by the leukemia-associated PML-RARα fusion protein. We show that in leukemic cells knockdown of SUZ12, a key component of Polycomb repressive complex 2 (PRC2), reverts not only histone modification but also induces DNA demethylation of PML-RARα target genes. This results in promoter reactivation and granulocytic differentiation. Importantly, the epigenetic alterations caused by PML-RARα can be reverted by retinoic acid treatment of primary blasts from leukemic patients. Our results demonstrate that the direct targeting of Polycomb group proteins by an oncogene plays a key role during carcinogenesis.
CELLCYCLE; DNA
Settore MED/04 - Patologia Generale
giu-2007
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/44630
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