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CD19-CD45 low/- CD38 high/CD138+ plasma cells enrich for human tumorigenic myeloma cells.
Leukemia. 2012 Dec; 26(12):2530-7.L

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(+)/CD38(high) cells from 40% of patients (8/20) led to a repopulation of CD19(+)CD38(low) or CD138(+)CD38(+) B-lineage cells in human bone grafts; and these grafts were clonally derived from patient myeloma cells. Meanwhile, CD19(+)CD38(low) xenografts were detected in human bone-bearing mice transplanted with CD19(+)CD38(low/-) B cells from 8 of 22 samples but were not clonally related to patient myeloma cells. Further fractionation and xenotransplantation of CD138(+)CD38(high) cells demonstrated that (CD45(low/-) or CD19(-)) CD38(high)/CD138(+) plasma cells, but not (CD45(high) or CD19(+)) CD38(high)/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(-)CD45(low/-) fully differentiated plasma cells enrich for long-lived and tumor-initiating cells whereas B cells or plasmablasts do not.

Authors+Show Affiliations

Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA. kimdk1@stanford.eduNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22733078

Citation

Kim, D, et al. "CD19-CD45 Low/- CD38 high/CD138+ Plasma Cells Enrich for Human Tumorigenic Myeloma Cells." Leukemia, vol. 26, no. 12, 2012, pp. 2530-7.
Kim D, Park CY, Medeiros BC, et al. CD19-CD45 low/- CD38 high/CD138+ plasma cells enrich for human tumorigenic myeloma cells. Leukemia. 2012;26(12):2530-7.
Kim, D., Park, C. Y., Medeiros, B. C., & Weissman, I. L. (2012). CD19-CD45 low/- CD38 high/CD138+ plasma cells enrich for human tumorigenic myeloma cells. Leukemia, 26(12), 2530-7. https://doi.org/10.1038/leu.2012.140
Kim D, et al. CD19-CD45 Low/- CD38 high/CD138+ Plasma Cells Enrich for Human Tumorigenic Myeloma Cells. Leukemia. 2012;26(12):2530-7. PubMed PMID: 22733078.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - CD19-CD45 low/- CD38 high/CD138+ plasma cells enrich for human tumorigenic myeloma cells. AU - Kim,D, AU - Park,C Y, AU - Medeiros,B C, AU - Weissman,I L, Y1 - 2012/05/30/ PY - 2012/6/27/entrez PY - 2012/6/27/pubmed PY - 2013/2/13/medline SP - 2530 EP - 7 JF - Leukemia JO - Leukemia VL - 26 IS - 12 N2 - 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(+)/CD38(high) cells from 40% of patients (8/20) led to a repopulation of CD19(+)CD38(low) or CD138(+)CD38(+) B-lineage cells in human bone grafts; and these grafts were clonally derived from patient myeloma cells. Meanwhile, CD19(+)CD38(low) xenografts were detected in human bone-bearing mice transplanted with CD19(+)CD38(low/-) B cells from 8 of 22 samples but were not clonally related to patient myeloma cells. Further fractionation and xenotransplantation of CD138(+)CD38(high) cells demonstrated that (CD45(low/-) or CD19(-)) CD38(high)/CD138(+) plasma cells, but not (CD45(high) or CD19(+)) CD38(high)/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(-)CD45(low/-) fully differentiated plasma cells enrich for long-lived and tumor-initiating cells whereas B cells or plasmablasts do not. SN - 1476-5551 UR - https://www.unboundmedicine.com/medline/citation/22733078/CD19_CD45_low/__CD38_high/CD138+_plasma_cells_enrich_for_human_tumorigenic_myeloma_cells_ L2 - https://doi.org/10.1038/leu.2012.140 DB - PRIME DP - Unbound Medicine ER -