| First Author | Lee SC | Year | 2013 |
| Journal | Blood | Volume | 122 |
| Issue | 15 | Pages | 2654-63 |
| PubMed ID | 23982173 | Mgi Jnum | J:203435 |
| Mgi Id | MGI:5527024 | Doi | 10.1182/blood-2013-02-484055 |
| Citation | Lee SC, et al. (2013) Polycomb repressive complex 2 (PRC2) suppresses Emu-myc lymphoma. Blood 122(15):2654-63 |
| abstractText | 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. |
