Polycomb repressive complex 2 (PRC2) suppresses Emu-myc lymphoma
- Author(s)
- Lee, SC; Phipson, B; Hyland, CD; Leong, HS; Allan, RS; Lun, A; Hilton, DJ; Nutt, SL; Blewitt, ME; Smyth, GK; Alexander, WS; Majewski, IJ;
- 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
- Research Division(s)
- Cancer And Haematology; Molecular Medicine; Bioinformatics; Molecular Immunology
- Link To PubMed Central Version
- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2449366/
- Publisher's Version
- https://doi.org/10.1182/blood-2013-02-484055
- NHMRC Grants
- NHMRC/1016647, NHMRC/575500, NHMRC/1011663,
- Terms of Use/Rights Notice
- © 2013 by The American Society of Hematology
Creation Date: 2014-01-24 12:02:23