title: 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.affiliation: Centre for Stem Cell Research, Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases (IMM), The University of Texas-Health Science Center at Houston, Houston, TX 77030, USA.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Chen
authors.forename: Paul
authors.initials: P
authors.lastname: Ayala
authors.forename: Michael
authors.initials: M
authors.lastname: Wang
authors.forename: Luis
authors.initials: L
authors.lastname: Fayad
authors.forename: Ruth L
authors.initials: RL
authors.lastname: Katz
authors.forename: Jorge
authors.initials: J
authors.lastname: Romaguera
authors.forename: Nancy
authors.initials: N
authors.lastname: Caraway
authors.forename: Sattva S
authors.initials: SS
authors.lastname: Neelapu
authors.forename: Larry W
authors.initials: LW
authors.lastname: Kwak
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Simmons
authors.forename: Nami
authors.initials: N
authors.lastname: McCarty
mesh_terms: D000818:Animals; D018941:Antigens, CD19 / Q000378:metabolism; D002469:Cell Separation; D006801:Humans; D017493:Leukocyte Common Antigens / Q000378:metabolism; D020522:Lymphoma, Mantle-Cell / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D016513:Mice, SCID; D014183:Transplantation, Heterologous
chemical_list: D018941:Antigens, CD19; D017493:Leukocyte Common Antigens