Prospective isolation of clonogenic mantle cell lymphoma-initiating cells.

Abstract

Here, we have prospectively isolated and characterized, for the first time, clonogenic cells with self-renewal capacities from mantle cell lymphoma (MCL), a particularly deadly form of non-Hodgkin's lymphoma (NHL). Self-renewal and tumorigenic activities were enriched in MCL cell fractions that lacked expression of the prototypic B-cell surface marker, CD19. CD45+CD19- cells represented a relatively small fraction of the total MCL tumor cells; however, they recapitulated the heterogeneity of original patient tumors on transplantation into immunodeficient mice. As few as 100 of these cells displayed self-renewal capacities in secondary and tertiary recipient mice by in vivo limiting dilution assays. Similar to leukemic stem cells, CD45+CD19- MCL cells also displayed a quiescent status as determined by dye efflux assays. In summary, this study is the first to isolate subpopulations of MCL cells that have self-renewal and tumorigenic capacities. Identification and characterization of MCL-ICs are important first steps toward understanding how self-renewal and tumorigenicity are regulated in MCL and designing targeted therapies against MCL-ICs will ultimately lead to improved outcomes for MCL patients.

• Authors: Zheng Chen, Paul Ayala, Michael Wang, Luis Fayad, Ruth L Katz, Jorge Romaguera, Nancy Caraway, Sattva S Neelapu, Larry W Kwak, Paul J Simmons, Nami McCarty
• Journal: Stem cell research (Stem Cell Res) Vol. 5 Issue 3 Pg. 212-25 (Nov 2010) ISSN: 1876-7753 [Electronic] England
• PMID: 20851072 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2010 Elsevier B.V. All rights reserved.

Chemical References

• Antigens, CD19
• Leukocyte Common Antigens

Topics

• Animals
• Antigens, CD19 (metabolism)
• Cell Separation
• Humans
• Leukocyte Common Antigens (metabolism)
• Lymphoma, Mantle-Cell (metabolism, pathology)
• Mice
• Mice, SCID
• Transplantation, Heterologous