CD19−CD45low/−CD38high/CD138+ plasma cells enrich for human tumorigenic myeloma cells
- 30 May 2012
- journal article
- research article
- Published by Springer Science and Business Media LLC in Leukemia
- Vol. 26 (12), 2530-2537
- https://doi.org/10.1038/leu.2012.140
Abstract
Multiple myeloma is a hematological neoplasm characterized by the accumulation of clonal plasma cells in the bone marrow. Its frequent relapse following achievement of clinical remissions implicates the existence of therapy-resistant myeloma-initiating cells. To date, results on the identity of myeloma-initiating cells have differed. Here, we prospectively identified a myeloma-initiating population by fractionating and transplanting patient bone marrow cells into human bone-bearing immunocompromised mice. Xenotransplantation of fractionated CD138+/CD38high cells from 40% of patients (8/20) led to a repopulation of CD19+CD38low or CD138+CD38+ B-lineage cells in human bone grafts; and these grafts were clonally derived from patient myeloma cells. Meanwhile, CD19+CD38low xenografts were detected in human bone-bearing mice transplanted with CD19+CD38low/− B cells from 8 of 22 samples but were not clonally related to patient myeloma cells. Further fractionation and xenotransplantation of CD138+CD38high cells demonstrated that (CD45low/− or CD19−) CD38high/CD138+ plasma cells, but not (CD45high or CD19+) CD38high/CD138+ plasmablasts enrich for myeloma-initiating cells. Quantitative reverse transcription-PCR of two serially transplantable xenografts, which were CD19−CD138+, revealed that they were Pax5 (a B-cell-specific transactivator)-negative. These results suggest that CD19−CD45low/− fully differentiated plasma cells enrich for long-lived and tumor-initiating cells whereas B cells or plasmablasts do not.Keywords
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