Progress in Hematology Basic and Clinical Updates in Multiple Myeloma

International Journal of Hematology

, Volume 97, Issue 3, pp 306-312

First online:

Multiple myeloma-initiating cells

  • Naoki HosenAffiliated withDepartments of Functional Diagnostic Science and Cancer Stem Cell Biology, Osaka University Graduate School of Medicine Email author 


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, CD19CD38++ 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.


Multiple myeloma Stem cell Progenitor cell Xenotransplant CD138