In summary, our study demonstrates the critical role of BAP1 in ASXL1-MT-induced aberrant myeloid differentiation, myeloid leukaemogenesis, and upregulation of HOXA genes and IRF8. Targeting enzymatic activity of BAP1 can be a promising therapeutic strategy for myeloid neoplasms with ASXL1 mutations, and potentially for a broad range of myeloid neoplasms with HOX dysregulation. The gene discussed is IRF8; the disease is myeloid neoplasm.