Hhex induces promyelocyte self-renewal and cooperates with growth factor independence to cause myeloid leukemia in mice.

ABSTRACT: The hematopoietically expressed homeobox (Hhex) transcription factor is overexpressed in human myeloid leukemias. Conditional knockout models of murine acute myeloid leukemia indicate that Hhex maintains leukemia stem cell self-renewal by enabling Polycomb-mediated epigenetic repression of the Cdkn2a tumor suppressor locus, encoding p16^Ink4a and p19^Arf However, whether Hhex overexpression also affects hematopoietic differentiation is unknown. To study this, we retrovirally overexpressed Hhex in hematopoietic progenitors. This enabled serial replating of myeloid progenitors, leading to the rapid establishment of interleukin-3 (IL-3)-dependent promyelocytic cell lines. Use of a Hhex-ERT2 fusion protein demonstrated that continuous nuclear Hhex is re

SUBMITTER: Jackson JT 

PROVIDER: S-EPMC5858476 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature