Unlocking the HOX: Homeobox Genes as Regulators of Hematopoietic Development

Homeobox (HOX) transcription factors are encoded within highly organized loci expressed along an anterior–posterior axis through embryogenesis and in a pleiotropic manner in hematopoiesis. HOX expression has been exhaustively studied in the context of oncogenesis and malignancy, but the compensatory substitution of HOX paralogs makes mechanistic annotation in steady-state hematopoiesis challenging. Despite this, HOX genes reflect numerous non-redundant roles in healthy hematopoiesis including HSC self-renewal, development, lymphopoiesis, myelopoiesis, and erythropoiesis. Here, we review historical and current insights into HOX functions in steady-state hematopoiesis and highlight unexplored avenues in their biology that could further elucidate their significance to hematopoietic homeostasis.