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Key Points • ASXL1 deletion in myeloid lineage cells promotes osteoclast differentiation resulting in low bone mass. • ASXL1 modulates H3K27 methylation of osteoclastogenic gene promoters, including NFATc1. Additional sex comb-like 1 (ASXL1) mutations are commonly associated with myeloid malignancies and are markers of aggressive disease. The fact that ASXL1 is necessary for myeloid differentiation raises the possibility it also regulates osteoclasts. We find deletion of ASXL1 in myeloid cellsdoi:10.1182/bloodadvances.2018018309 fatcat:mzshbwunvfdr3jzq3z3vnevnqq