Homeobox protein Hox-A cluster (HOXA)

The Homeobox protein Hox-A cluster (HOXA) is a group of 11 highly conserved transcription factors located on chromosome 7p15.2 that are fundamental to embryonic development and positional identity [Wikipedia]. These proteins contain a characteristic 60-amino acid homeodomain that binds to specific DNA sequences to regulate genes involved in morphogenesis and cell differentiation [UniProt]. In adult physiology, members of the HOXA cluster, particularly HOXA9, are essential for the maintenance and differentiation of hematopoietic stem cells [PubMed: 30310040]. Dysregulation of the HOXA cluster is a significant driver in several cancers; for instance, the overexpression of HOXA9 and HOXA10 is a hallmark of aggressive leukemias harboring MLL (KMT2A) rearrangements or NPM1 mutations [PubMed: 28254383]. While direct targeting of transcription factors is challenging, the HOXA cluster is currently targeted indirectly through Menin-MLL inhibitors like Revumenib, which disrupt the epigenetic complexes required for HOXA transcription [ClinicalTrials.gov]. Additionally, experimental peptides like HXR9 aim to disrupt the interaction between HOX proteins and their required PBX cofactors to induce apoptosis in cancer cells [PubMed: 25151357].

Other names

HOX1 clusterHomeobox A clusterHOXA1-HOXA13HOXA gene cluster

Inhibition of the Menin-KMT2A (MLL) interaction to downregulate HOXA gene expression; disruption of HOX-PBX protein-protein interactions to prevent transcriptional activity.