Overexpression of sPRDM16 coupled with loss of p53 induces myeloid leukemias in mice.

ABSTRACT: Transgenic expression of the abnormal products of acute myeloid leukemia-associated (AML-associated) primary chromosomal translocations in hematopoietic stem/progenitor cells initiates leukemogenesis in mice, yet additional mutations are needed for leukemia development. We report here aberrant expression of PR domain containing 16 (PRDM16) in AML cells with either translocations of 1p36 or normal karyotype. These carried, respectively, relatively high prevalence of mutations in the TP53 tumor suppressor gene and in the nucleophosmin (NPM) gene, which regulates p53. Two protein isoforms are expressed from PRDM16, which differ in the presence or absence of the PR domain. Overexpression of the short isoform, sPRDM16, in mouse bone marrow induced AML with full penetrance, but only in the absen

SUBMITTER: Shing DC 

PROVIDER: S-EPMC2082144 | biostudies-literature | 2007 Dec

REPOSITORIES: biostudies-literature