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Role of the Polycomb Repressive Complex 2 in Acute Promyelocytic Leukemia

Jun 12, 2007 cancer

New research published today in the journal Cancer Cell by Villa et al. sheds new light on the interaction between two gene regulation mechanisms: DNA methylation and the Polycomb protein complex.

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-RAR 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-RAR target genes. This results in promoter reactivation and granulocytic differentiation. Importantly, the epigenetic alterations caused by PML-RAR 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.

innovations-report has a nice summary of previous work done in this area and the significance of the current paper.

The featured article in the June issue is available for free. Link

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One Response to “Role of the Polycomb Repressive Complex 2 in Acute Promyelocytic Leukemia”

  1. Cells Weekly #34 « Migrations Says:

    June 17th, 2007 at 7:52 am

    [...] Role of the Polycomb Repressive Complex 2 in Acute Promyelocytic Leukemia [...]