In acute myeloid leukaemia (AML), accumulating leukaemic blasts occupy specialized niches in the bone marrow (BM). However, the extent to which normal haematopoiesis is affected in AML cannot be fully accounted for by this anatomical crowding of the BM. Boyd et al. found that the adipocyte BM niche is disrupted in human AML, causing defective myelo-erythroid maturation of haematopoietic stem and progenitor cells (HSPCs). Analysis of AML patient samples through in vitro co-culture and patient-derived xenografts (PDXs) in mice identified that BM adipogenesis was disrupted in AML. Whereas normal HSPCs promoted adipogenesis of mesenchymal stem cells (MSCs) in co-culture, leukaemic cells inhibited adipogenesis of MSCs. Adipogenesis in the BM was also severely impaired in PDXs. Importantly, pro-adipogenic therapy restored the adipocyte BM niche, protected normal haematopoiesis and repressed leukaemic growth in PDXs.