Grant-in-Aid for Scientific Research (A)
We demonstrated that the polycomb gene Ezh2 is required to promote MLL-AF9-driven acute myeloid leukemia (AML) in mice (Blood 120:1107, 2012). In contrast, we also found that the hematopoietic-specific deletion of Ezh2 in mice induced heterogeneous hematopoietic malignancies, including myelodysplastic syndrome (MDS), MDS/myeloproliferative neoplasms (MDS/MPN), and T-ALL after a long latency. Furthermore, the concurrent depletion of Ezh2 and Tet2 in mice markedly accelerated the development of MDS and MDS/MPN and Ezh2 loss significantly promoted RUNX1S291fs-induced MDS (J Exp Med 210:2627, 2013; Nat Commun 5:4177, 2014). These findings support the tumor suppressor function of EZH2 in the context of myelodysplastic disorders and well correspond to the identification of recurrent inactivating mutations in EZH2 in patients with MDS, MPN, MDS/MPN, and T-ALL.
Stem cell reports
J Exp Med.
Volume: in press
Attribution of KAKENHI