Reduced PU.1 expression causes myeloid progenitor expansion and increased leukemia penetrance in mice expressing PML-RARalpha.

ABSTRACT: PU.1 is a member of the ETS family of transcription factors that is known to be important for hematopoietic development. Recently, haploinsufficiency for PU.1 has been shown to cause a shift in myelomonocytic progenitor fate toward the myeloid lineage. We have previously shown that transgenic mice expressing PML-RARalpha (PR) and RARalpha-PML frequently develop acute promyelocytic leukemia (APL) in association with a large (>20 Mb) interstitial deletion of chromosome 2 that includes PU.1. To directly assess the relevance of levels of expression of PU.1 for leukemia progression, we bred hCG-PR mice with PU.1+/- mice and assessed their phenotype. Young, nonleukemic hCG-PR x PU.1+/- mice developed splenomegaly because of the abnormal expansion of myeloid cells in their spleens. hCG-PR x PU.1+

SUBMITTER: Walter MJ 

PROVIDER: S-EPMC1188022 | biostudies-literature | 2005 Aug

REPOSITORIES: biostudies-literature