HOX homeobox genes play a role both in the early stem cell function as well as in later stages of hematopoietic differentiation. HOXB4, specifically, is a homeotic selector gene implicated in self-renewal of definitive HSCs. Expression of HOXB4 in primitive progenitors combined with culture on hematopoietic stroma induced a switch to the definitive HSC phenotype. Activation of WNT signaling in HSCs induced increased expression of HOXB4. Perturbations of HOX gene expression can cause leukemia.