Leptin, secreted by adipocytes in bone marrow stimulates proliferation of acute myeloid leukemia cells. PML-RARalpha-expressing acute promyelocytic leukemia (APL) cells express high levels of leptin receptor (OB-R). Adipocytes derived from mesenchymal stem cells (MSC) protect APL cells from drug-induced apoptosis partially through the interaction of the membrane-bound form of leptin and OB-R. We report that when NB4 APL cells migrated beneath a cultured MSC-derived adipocyte layer, apoptosis in most of the cells below the adipocytes was blocked. Major histocompatibility complex (MHC) expression of NB4 cells and MSCs matched (both were HLA-DR negative and HLA-ABC positive). This match in MHC expression may play a role in the intimate cell-to-cell interactions that support the anti-apoptotic effects of the membrane-bound leptin signaling pathway.