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, Chong Jie Zhang, Lesleyann Hawthorn, John K. Cowell, Julian L. Ambrus*

*Corresponding author for this work

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

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 14α (IL-14α) transgenic mice with c-Myc transgenic mice (double transgenic [DTG]). IL-14α is a B-cell growth factor that is expressed in a number of high-grade lymphomas, including MCL-BV. Ninety-five percent of IL-14α 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.

Original languageEnglish (US)
Pages (from-to)4899-4906
Number of pages8
JournalBlood
Volume109
Issue number11
DOIs
StatePublished - Jun 1 2007

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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  • Cite this

    Ford, R. J., Shen, L., Lin-Lee, Y. C., Pham, L. V., Multani, A., Zhou, H. J., Tamayo, A. T., Zhang, C. J., Hawthorn, L., Cowell, J. K., & Ambrus, J. L. (2007). Development of a murine model for blastoid variant mantle-cell lymphoma. Blood, 109(11), 4899-4906. https://doi.org/10.1182/blood-2006-08-038497