Prospective isolation of clonogenic mantle cell lymphoma-initiating cells.
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.
Chen
Zheng
Z
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.
Ayala
Paul
P
Wang
Michael
M
Fayad
Luis
L
Katz
Ruth L
RL
Romaguera
Jorge
J
Caraway
Nancy
N
Neelapu
Sattva S
SS
Kwak
Larry W
LW
Simmons
Paul J
PJ
McCarty
Nami
N
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
D018941:Antigens, CD19; D017493:Leukocyte Common Antigens