Cobblestone-area forming cells derived from patients with mantle cell lymphoma are enriched for CD133+ tumor-initiating cells.
Mantle cell lymphoma (MCL) is associated with a significant risk of therapeutic failure and disease relapse, but the biological origin of relapse is poorly understood. Here, we prospectively identify subpopulations of primary MCL cells with different biologic and immunophenotypic features. Using a simple culture system, we demonstrate that a subset of primary MCL cells co-cultured with either primary human mesenchymal stromal cells (hMSC) or murine MS-5 cells form in cobblestone-areas consisting of cells with a primitive immunophenotype (CD19-CD133+) containing the chromosomal translocation t (11;14)(q13;q32) characteristic of MCL. Limiting dilution serial transplantation experiments utilizing immunodeficient mice revealed that primary MCL engraftment was only observed when either unsorted or CD19-CD133+ cells were utilized. No engraftment was seen using the CD19+CD133- subpopulation. Our results establish that primary CD19-CD133+ MCL cells are a functionally distinct subpopulation of primary MCL cells enriched for MCL-initiating activity in immunodeficient mice. This rare subpopulation of MCL-initiating cells may play an important role in the pathogenesis of MCL.
Department of Medicine, Rutgers - The State University of New Jersey, Robert Wood Johnson Medical School, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, United States of America.
Daniel J
DJ
Medina
Department of Medicine, Rutgers - The State University of New Jersey, Robert Wood Johnson Medical School, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, United States of America.
Jeneba
J
Abass-Shereef
Department of Medicine, Rutgers - The State University of New Jersey, Robert Wood Johnson Medical School, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, United States of America.
Kelly
K
Walton
Department of Pathology, Rutgers - The State University of New Jersey, Robert Wood Johnson Medical School, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, United States of America.
Lauri
L
Goodell
Department of Pathology, Rutgers - The State University of New Jersey, Robert Wood Johnson Medical School, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, United States of America.
Hana
H
Aviv
Department of Medicine, Rutgers - The State University of New Jersey, Robert Wood Johnson Medical School, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, United States of America.
Roger K
RK
Strair
Department of Medicine, Rutgers - The State University of New Jersey, Robert Wood Johnson Medical School, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, United States of America.
Tulin
T
Budak-Alpdogan
D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D018941:Antigens, CD19 / Q000378:metabolism; D018920:Coculture Techniques / Q000379:methods; D003470:Culture Media; D015972:Gene Expression Regulation, Neoplastic; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D016130:Immunophenotyping; D017493:Leukocyte Common Antigens / Q000378:metabolism; D020522:Lymphoma, Mantle-Cell / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000166:cytology*; D010455:Peptides / Q000378:metabolism*; D017154:Stromal Cells; D014178:Translocation, Genetic
D000071916:AC133 Antigen; D015703:Antigens, CD; D018941:Antigens, CD19; D003470:Culture Media; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse; D017493:Leukocyte Common Antigens; C516769:PTPRC protein, human