Role of the Polycomb Repressive Complex 2 in Acute Promyelocytic Leukemia

Raffaella Villa, Diego Pasini, Arantxa Gutierrez, Lluis Morey, Manuela Occhionorelli, Emmanuelle Viré, Josep F. Nomdedeu, Thomas Jenuwein, Pier Giuseppe Pelicci, Saverio Minucci, Francois Fuks, Kristian Helin, Luciano Di Croce

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)513-525
Number of pages13
JournalCancer Cell
Volume11
Issue number6
DOIs
Publication statusPublished - Jun 12 2007

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Keywords

  • CELLCYCLE
  • DNA

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Oncology

Cite this

Villa, R., Pasini, D., Gutierrez, A., Morey, L., Occhionorelli, M., Viré, E., Nomdedeu, J. F., Jenuwein, T., Pelicci, P. G., Minucci, S., Fuks, F., Helin, K., & Di Croce, L. (2007). Role of the Polycomb Repressive Complex 2 in Acute Promyelocytic Leukemia. Cancer Cell, 11(6), 513-525. https://doi.org/10.1016/j.ccr.2007.04.009