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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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NEOPLASIA
Development of a murine model for blastoid variant mantle-cell lymphoma
Richard J. Ford1,
Long Shen2,
Yen Chiu Lin-Lee1,
Lan V. Pham1,
Asha Multani1,
Hai-Jun Zhou1,
Archito T. Tamayo1,
ChongJie Zhang2,3,
Lesleyann Hawthorn4,
John K. Cowell4, and
Julian L. Ambrus, Jr2
1 The Department of Hematopathology, University of Texas M. D. Anderson Cancer Center, Houston;
2 Division of Allergy, Immunology, and Rheumatology, Department of Medicine, State University of New York (SUNY) at Buffalo School of Medicine and Biomedical Sciences and Kaleida Health;
3 Department of Immunology, Sichuan University, Chengdu, Sichuan, People's Republic of China;
4 Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY
Blastoid-variant mantle-cell lymphoma (MCL-BV), unlike most B-cell non-Hodgkin lymphomas (NHL-Bs), 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 to 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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