Polycomb repressive complex 2 (PRC2) suppresses Emu-myc lymphoma
Details
Publication Year 2013-10-10, Volume 122, Issue #15, Page 2654-63
Journal Title
Blood
Publication Type
Journal Article
Abstract
Deregulation of polycomb group complexes polycomb repressive complex 1 (PRC1) and 2 (PRC2) is associated with human cancers. Although inactivating mutations in PRC2-encoding genes EZH2, EED, and SUZ12 are present in T-cell acute lymphoblastic leukemia and in myeloid malignancies, gain-of-function mutations in EZH2 are frequently observed in B-cell lymphoma, implying disease-dependent effects of individual mutations. We show that, in contrast to PRC1, PRC2 is a tumor suppressor in Emicro-myc lymphomagenesis, because disease onset was accelerated by heterozygosity for Suz12 or by short hairpin RNA-mediated knockdown of Suz12 or Ezh2. Accelerated lymphomagenesis was associated with increased accumulation of B-lymphoid cells in the absence of effects on apoptosis or cell cycling. However, Suz12-deficient B-lymphoid progenitors exhibit enhanced serial clonogenicity. Thus, PRC2 normally restricts the self-renewal of B-lymphoid progenitors, the disruption of which contributes to lymphomagenesis. This finding provides new insight regarding the functional contribution of mutations in PRC2 in a range of leukemias.
Publisher
AMER SOC HEMATOLOGY
WEHI Research Division(s)
Cancer And Haematology; Molecular Medicine; Bioinformatics; Molecular Immunology
NHMRC Grants
NHMRC/1016647 NHMRC/575500 NHMRC/1011663
Rights Notice
© 2013 by The American Society of Hematology


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Last Modified: 0001-01-01 12:00:00
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