Spontaneous migration of acute promyelocytic leukemia cells beneath cultured bone marrow adipocytes with matched expression of the major histocompatibility complex.
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.
Tabe
Yoko
Y
Blood and Marrow Transplantation, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Konopleva
Marina
M
Igari
Jun
J
Andreeff
Michael
M
D017667:Adipocytes / Q000378:metabolism / Q000502:physiology*; D017209:Apoptosis; D001854:Bone Marrow Cells / Q000166:cytology*; D002465:Cell Movement; D002478:Cells, Cultured; D006801:Humans; D020738:Leptin / Q000378:metabolism / Q000502:physiology; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D008285:Major Histocompatibility Complex / Q000502:physiology*; D059630:Mesenchymal Stem Cells / Q000166:cytology; D009363:Neoplasm Proteins / Q000378:metabolism*; D015514:Oncogene Proteins, Fusion / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000502:physiology; D054411:Receptors, Leptin; D015398:Signal Transduction
D020738:Leptin; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein