title: CD138-negative clonogenic cells are plasma cells but not B cells in some multiple myeloma patients.
abstract: Clonogenic multiple myeloma (MM) cells reportedly lacked expression of plasma cell marker CD138. It was also shown that CD19(+) clonotypic B cells can serve as MM progenitor cells in some patients. However, it is unclear whether CD138-negative clonogenic MM plasma cells are identical to clonotypic CD19(+) B cells. We found that in vitro MM colony-forming cells were enriched in CD138(-)CD19(-)CD38(++) plasma cells, while CD19(+) B cells never formed MM colonies in 16 samples examined in this study. We next used the SCID-rab model, which enables engraftment of human MM in vivo. CD138(-)CD19(-)CD38(++) plasma cells engrafted in this model rapidly propagated MM in 3 out of 9 cases, while no engraftment of CD19(+) B cells was detected. In 4 out of 9 cases, CD138(+) plasma cells propagated MM, although more slowly than CD138(-) cells. Finally, we transplanted CD19(+) B cells from 13 MM patients into NOD/SCID IL2Rγc(-/-) mice, but MM did not develop. These results suggest that at least in some MM patients CD138-negative clonogenic cells are plasma cells rather than B cells, and that MM plasma cells including CD138(-) and CD138(+) cells have the potential to propagate MM clones in vivo in the absence of CD19(+) B cells.
authors.affiliation: Department of Cancer Stem Cell Biology, Osaka, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Hosen
authors.forename: Y
authors.initials: Y
authors.lastname: Matsuoka
authors.forename: S
authors.initials: S
authors.lastname: Kishida
authors.forename: J
authors.initials: J
authors.lastname: Nakata
authors.forename: Y
authors.initials: Y
authors.lastname: Mizutani
authors.forename: K
authors.initials: K
authors.lastname: Hasegawa
authors.forename: A
authors.initials: A
authors.lastname: Mugitani
authors.forename: H
authors.initials: H
authors.lastname: Ichihara
authors.forename: Y
authors.initials: Y
authors.lastname: Aoyama
authors.forename: S
authors.initials: S
authors.lastname: Nishida
authors.forename: A
authors.initials: A
authors.lastname: Tsuboi
authors.forename: F
authors.initials: F
authors.lastname: Fujiki
authors.forename: N
authors.initials: N
authors.lastname: Tatsumi
authors.forename: H
authors.initials: H
authors.lastname: Nakajima
authors.forename: M
authors.initials: M
authors.lastname: Hino
authors.forename: T
authors.initials: T
authors.lastname: Kimura
authors.forename: K
authors.initials: K
authors.lastname: Yata
authors.forename: M
authors.initials: M
authors.lastname: Abe
authors.forename: Y
authors.initials: Y
authors.lastname: Oka
authors.forename: Y
authors.initials: Y
authors.lastname: Oji
authors.forename: A
authors.initials: A
authors.lastname: Kumanogoh
authors.forename: H
authors.initials: H
authors.lastname: Sugiyama
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016026:Bone Marrow Transplantation; D003114:Colony-Forming Units Assay; D006801:Humans; D016130:Immunophenotyping; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009101:Multiple Myeloma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D010950:Plasma Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D011817:Rabbits; D053668:Syndecan-1 / Q000378:metabolism*
chemical_list: C508241:SDC1 protein, human; D053668:Syndecan-1