USP22 deficiency leads to myeloid leukemia upon oncogenic Kras activation through a PU.1-dependent mechanism.

ABSTRACT: Ras mutations are commonly observed in juvenile myelomonocytic leukemia (JMML) and chronic myelomonocytic leukemia (CMML). JMML and CMML transform into acute myeloid leukemia (AML) in about 10% and 50% of patients, respectively. However, how additional events cooperate with Ras to promote this transformation are largely unknown. We show that absence of the ubiquitin-specific peptidase 22 (USP22), a component of the Spt-Ada-GCN5-acetyltransferase chromatin-remodeling complex that is linked to cancer progression, unexpectedly promotes AML transformation in mice expressing oncogenic Kras^G12D/+ USP22 deficiency in Kras^G12D/+ mice resulted in shorter survival compared with control mice. This was due to a block in myeloid cell differentiat

SUBMITTER: Melo-Cardenas J 

PROVIDER: S-EPMC6071563 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature