Role of the polycomb repressive complex 2 in acute promyelocytic leukemia.

TY - JOUR

T1 - Role of the polycomb repressive complex 2 in acute promyelocytic leukemia.

AU - Villa, Raffaella

AU - Pasini, Diego

AU - Gutierrez, Arantxa

AU - Morey, Lluis

AU - Occhionorelli, Manuela

AU - Viré, Emmanuelle

AU - Nomdedeu, Josep F

AU - Jenuwein, Thomas

AU - Pelicci, Pier Giuseppe

AU - Minucci, Saverio

AU - Fuks, Francois

AU - Helin, Kristian

AU - Di Croce, Luciano

N1 - Keywords: Carrier Proteins; Cell Differentiation; DNA Methylation; Epigenesis, Genetic; Gene Silencing; Granulocytes; Histones; Humans; Leukemia, Promyelocytic, Acute; Nuclear Proteins; Oncogene Proteins, Fusion; Repressor Proteins; Tretinoin; Tumor Cells, Cultured

PY - 2007

Y1 - 2007

N2 - 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-RARalpha 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-RARalpha target genes. This results in promoter reactivation and granulocytic differentiation. Importantly, the epigenetic alterations caused by PML-RARalpha 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.

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

U2 - 10.1016/j.ccr.2007.04.009

DO - 10.1016/j.ccr.2007.04.009

M3 - Journal article

C2 - 17560333

SN - 1535-6108

VL - 11

SP - 513

EP - 525

JO - Cancer Cell

JF - Cancer Cell

IS - 6

ER -