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 Kenneth Cowell, Julian L. Ambrus

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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
Externally publishedYes

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Mantle-Cell Lymphoma
Transgenic Mice
Tumors
Cells
Interleukins
B-Cell Lymphoma
Chemotherapy
Non-Hodgkin's Lymphoma
Cyclin D1
Cell growth
Lymphoma
Liver
Refractory materials
Immunoglobulins
Brain
Intercellular Signaling Peptides and Proteins
Bone
Animals
Blood
Genes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Ford, R. J., Shen, L., Lin-Lee, Y. C., Pham, L. V., Multani, A., Zhou, H. J., ... 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

Development of a murine model for blastoid variant mantle-cell lymphoma. / Ford, Richard J.; Shen, Long; Lin-Lee, Yen Chiu; Pham, Lan V.; Multani, Asha; Zhou, Hai Jun; Tamayo, Archito T.; Zhang, Chong Jie; Hawthorn, Lesleyann; Cowell, John Kenneth; Ambrus, Julian L.

In: Blood, Vol. 109, No. 11, 01.06.2007, p. 4899-4906.

Research output: Contribution to journalArticle

Ford, RJ, Shen, L, Lin-Lee, YC, Pham, LV, Multani, A, Zhou, HJ, Tamayo, AT, Zhang, CJ, Hawthorn, L, Cowell, JK & Ambrus, JL 2007, 'Development of a murine model for blastoid variant mantle-cell lymphoma', Blood, vol. 109, no. 11, pp. 4899-4906. https://doi.org/10.1182/blood-2006-08-038497
Ford RJ, Shen L, Lin-Lee YC, Pham LV, Multani A, Zhou HJ et al. Development of a murine model for blastoid variant mantle-cell lymphoma. Blood. 2007 Jun 1;109(11):4899-4906. https://doi.org/10.1182/blood-2006-08-038497
Ford, Richard J. ; Shen, Long ; Lin-Lee, Yen Chiu ; Pham, Lan V. ; Multani, Asha ; Zhou, Hai Jun ; Tamayo, Archito T. ; Zhang, Chong Jie ; Hawthorn, Lesleyann ; Cowell, John Kenneth ; Ambrus, Julian L. / Development of a murine model for blastoid variant mantle-cell lymphoma. In: Blood. 2007 ; Vol. 109, No. 11. pp. 4899-4906.
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