Conditional knockout models of murine acute myeloid leukemia indicate that <i>Hhex</i> maintains leukemia stem cell self-renewal by enabling Polycomb-mediated epigenetic repression of the Cdkn2a tumor suppressor locus, encoding p16<sup>Ink4a</sup> and p19<sup>Arf</sup> However, whether <i>Hhex</i> overexpression also affects hematopoietic differentiation is unknown.