The data we have presented herein demonstrate that heterozygous deletion of Kdm6b blocks the development of ASXL1 mutation–mediated myeloid malignancies, and that the KDM6B inhibitor GSK-J4 likewise attenuates ASXL1-mutated leukemic cell growth and tumor burden in preclinical mouse models. Here, ASXL1 is linked to myeloid neoplasm.