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Blood, 1 June 2007, Vol. 109, No. 11, pp. 4899-4906.
Prepublished online as a Blood First Edition Paper on February 20, 2007; DOI 10.1182/blood-2006-08-038497.
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Submitted August 2, 2006
Accepted February 12, 2007
Development of a murine model for blastoid variant mantle cell lymphoma
Richard J Ford, Long Shen, Yen Chiu Lin-Lee, Lan V Pham, Asha Multani, Hai-Jun Zhou, Archito T Tamayo, ChongJie Zhang, Lesleyann Hawthorn, John K Cowell, and Julian L Ambrus Jr.*
Department of Hematopathology, University of Texas MD Anderson Cancer Center, Houston, TX, United States
Division of Allergy, Immunology and Rheumatology, Department of Medicine, SUNY at Buffalo School of Medicine and Biomedical Sciences & Kaleida Health, Buffalo, NY, United States
Department of Immunology, Sichuan University, Chengdu, China
Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY, United States
* Corresponding author; email: jambrus{at}buffalo.edu.
Blastoid Variant Mantle Cell lymphoma (MCL-BV), unlike most B cell non-Hodgkin's lymphomas (NHL-B), is refractory to conventional chemotherapy, and associated with a very poor prognosis. Development of new therapies has been hampered by the lack of valid animal models. We have developed a novel murine model of MCL-BV by crossing Interleukin 14 (IL-14) transgenic mice with c-Myc transgenic mice (Double transgenic - DTG). IL-14 is a B cell growth factor that is expressed in a number of high-grade lymphomas, including MCL-BV. Ninety-five percent of IL-14 transgenic mice develop CD5+ large B cell lymphomas by 18 months of age. Sixty percent of c-Myc transgenic mice develop pre-B cell lymphomas by 12 months of age. Close to 100% of DTG mice develop an aggressive, rapidly fatal lymphoma at 3-4 months of age that is CD5+, CD19+, CD21-, CD23-, sIgM +. The tumor is found in the blood, bone marrow, liver, spleen, lymph nodes, gastrointestinal tract, and lungs and rarely in the brain, similar to the involvement seen in human MCL-BV. Immunoglobulin gene rearrangements document the monoclonality of the tumor. Cyclin D1 is highly expressed in these tumors as it is in MCL-BV. DTG represents a novel model for MCL-BV that should reveal important insights into the pathogenesis of the lymphoma and contribute to the development of new forms of therapy.
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