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Title

Competition between clonal plasma cells and normal cells for potentially overlapping bone marrow niches is associated with a progressively altered cellular distribution in MGUS vs myeloma

AuthorsPaiva, Bruno; Pérez-Andrés, Martin; Almeida, Julia ; Mateos, Maria Victoria; López-Corral, L.; Gutiérrez, Norma Carmen; Schmidt-Hieber, M.; Lahuerta, Juan José; San Miguel, Jesús F. ; Orfao, Alberto
Issue Date2011
PublisherNature Publishing Group
CitationLeukemia 25: 697-706 (2011)
AbstractDisappearance of normal bone marrow (BM) plasma cells (PC) predicts malignant transformation of monoclonal gammopathy of undetermined significance (MGUS) and smoldering myeloma (SMM) into symptomatic multiple myeloma (MM). The homing, behavior and survival of normal PC, but also CD34 hematopoietic stem cells (HSC), B-cell precursors, and clonal PC largely depends on their interaction with stromal cell-derived factor-1 (SDF-1) expressing, potentially overlapping BM stromal cell niches. Here, we investigate the distribution, phenotypic characteristics and competitive migration capacity of these cell populations in patients with MGUS, SMM and MM vs healthy adults (HA) aged 60 years. Our results show that BM and peripheral blood (PB) clonal PC progressively increase from MGUS to MM, the latter showing a slightly more immature immunophenotype. Of note, such increased number of clonal PC is associated with progressive depletion of normal PC, B-cell precursors and CD34 HSC in the BM, also with a parallel increase in PB. In an ex vivo model, normal PC, B-cell precursors and CD34 HSC from MGUS and SMM, but not MM patients, were able to abrogate the migration of clonal PC into serial concentrations of SDF-1. Overall, our results show that progressive competition and replacement of normal BM cells by clonal PC is associated with more advanced disease in patients with MGUS, SMM and MM. © 2011 Macmillan Publishers Limited All rights reserved.
URIhttp://hdl.handle.net/10261/59867
DOI10.1038/leu.2010.320
Identifiersdoi: 10.1038/leu.2010.320
issn: 0887-6924
e-issn: 1476-5551
Appears in Collections:(IBMCC) Artículos
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