title: A severe combined immunodeficient-hu in vivo mouse model of human primary mantle cell lymphoma.
abstract: OBJECTIVE
  To establish a severe combined immunodeficient (SCID)-hu in vivo mouse model of human primary mantle cell lymphoma (MCL) for the study of the biology and novel therapy of human MCL.
  
  
  METHODS
  Primary MCL cells were isolated from spleen, lymph node, bone marrow aspirates, or peripheral blood of six different patients and injected respectively into human bone chips, which had been s.c. implanted in SCID-hu. Circulating human beta(2)-microglobulin in mouse serum was used to monitor the engraftment and growth of patient's MCL cells. H&E staining and immunohistochemical staining with anti-human CD20 and cyclin D1 antibodies were used to confirm the tumor growth and migration.
  
  
  RESULTS
  Increasing levels of circulating human beta(2)-microglobulin in mouse serum indicated that the patient's MCL cells were engrafted successfully into human bone chip of SCID-hu mice. The engraftment and growth of patient's MCL cells were dependent on human bone marrow microenvironment. Immunohistochemical staining with anti-human CD20 and cyclin D1 antibodies confirmed that patient's MCL cells were able to not only survive and propagate in the bone marrow microenvironment of the human fetal bone chips, but also similar to the human disease, migrate to lymph nodes, spleen, bone marrow, and gastrointestinal tract of host mice. Treatment of MCL-bearing SCID-hu mice with atiprimod, a novel antitumor compound against the protection of bone marrow stromal cells, induced tumor regression.
  
  
  CONCLUSIONS
  This is the first human primary MCL animal model that should be useful for the biological and therapeutic research on MCL.
authors.affiliation: Department of Lymphoma and Myeloma, Division of Cancer Medicine, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Wang
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Han
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.forename: Jianfei
authors.initials: J
authors.lastname: Qian
authors.forename: Sungyoul
authors.initials: S
authors.lastname: Hong
authors.forename: Pei
authors.initials: P
authors.lastname: Lin
authors.forename: Yuankai
authors.initials: Y
authors.lastname: Shi
authors.forename: Jorge
authors.initials: J
authors.lastname: Romaguera
authors.forename: Larry W
authors.initials: LW
authors.lastname: Kwak
authors.forename: Qing
authors.initials: Q
authors.lastname: Yi
mesh_terms: D000368:Aged; D000818:Animals; D016025:Bone Transplantation / Q000379:methods; D001842:Bone and Bones; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D020522:Lymphoma, Mantle-Cell / Q000473:pathology*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D009368:Neoplasm Transplantation / Q000379:methods; D001613:beta 2-Microglobulin / Q000097:blood
chemical_list: D001613:beta 2-Microglobulin