title: Multiple myeloma-initiating cells.
abstract: Multiple myeloma (MM) is characterized by the clonal expansion of malignant plasma cells. As in other cancers, MM plasma cells are thought to be derived from MM-initiating cells, although these remain unidentified. MM patients harbor phenotypic CD19(+) B cells expressing the immunoglobulin gene sequence and the idiotype unique to the individual myeloma clone. Some previous studies have reported that CD19(+) clonotypic B cells can serve as MM-initiating cells. However, we and another group have recently showed that CD19(+) B cells from many MM patients do not reconstitute MM disease upon transplantation into NOD/SCID IL2Rγc(-/-) mice. In the SCID-rab and SCID-hu models, which enable engraftment of human MM in vivo, CD19(-)CD38(++) plasma cells engrafted and rapidly propagated MM, while engraftment of CD19(+) B cells was not detected. Both CD138(-) and CD138(+) plasma cells have the potential to propagate MM clones in vivo in the absence of CD19(+) B cells. Distinct from acute myeloid leukemia-initiating cells, which are derived from undifferentiated stem or progenitor cells, MM-initiating cells are derived from plasma cells, which are terminally differentiated cells. An improved understanding of how the bone marrow microenvironment supports MM-initiating plasma cells, which can initiate MM disease in the SCID-hu (or rab) model, is thus now essential.
authors: Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine, 1-7 Yamada-Oka, Suita, Osaka, 565-0871, Japan. hnaoki@imed3.med.osaka-u.ac.jp
authors: Naoki
authors: N
authors: Hosen
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D009101:Multiple Myeloma / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D010950:Plasma Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D059016:Tumor Microenvironment