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A Severe Combined Immunodeficient–hu In vivo Mouse Model of Human Primary Mantle Cell Lymphoma

Authors' Affiliations: ¹ Department of Lymphoma and Myeloma, Division of Cancer Medicine, and ² Department of Hematopathology, Division of Pathology and Laboratory Medicine, The University of Texas M. D. Anderson Cancer Center, Houston, Texas; and ³ Department of Medical Oncology, Cancer Institute/Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

Requests for reprints: Qing Yi, Department of Lymphoma and Myeloma, M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 0903, Houston, TX 77030. Phone: 713-563-9065; Fax: 713-563-9241; E-mail: qyi{at}mdanderson.org.

Purpose: 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.

Experimental Design: 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 β₂-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 β₂-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.

Conclusion: This is the first human primary MCL animal model that should be useful for the biological and therapeutic research on MCL.