New Mouse Model Promotes Study of B-Cell Lymphomas

Cancer researchers have created a genetically engineered mouse model that enables the study of factors that contribute to the transformation of normal B-cells into the cancerous cells that make up B-cell lymphomas.

Non-hodgkins lymphomas, about 90% of which are B-cell lymphomas, have become 85% more prevalent in the past 20 years, the only major form of cancer to experience such growth. Recent studies have pointed to the involvement of the cell surface B-cell receptor (BCR) together with the potent MYC oncogene.

Investigators at National Jewish Medical and Research Center (Denver, CO, USA) genetically engineered a line of mice to express a single B-cell clone. They then determined the type of cancer that developed when B-cells that overexpressed MYC were stimulated with a foreign antigen, an autoantigen, or with no antigen at all.

Results published in the June 24, 2008, issue of the journal PLos Biology revealed that when no antigen was present, the mice developed a lymphoma similar to human B-cell lymphocytic leukemia. When there was an antigen to bind to the B-cell receptor, the mice developed lymphomas that closely resembled Burkitt's lymphoma tumors that were dependent on both MYC and the antigen for survival and proliferation.

Development of tumors could be prevented, and already existing tumors eliminated by treating the mice with immunosuppressants that blocked signals from the B-cell receptor.

"Research into B-cell lymphomas has been hampered by the lack of a good mouse model,” said first author Dr. Yosef Refaeli, assistant professor of pediatrics at National Jewish Medical and Research Center. "The mouse we created gives us a very good, predictive model of B-cell lymphomas, which can be used to explore not only these and related cancers, but also autoimmune disease and basic immunology. Our findings have pointed to the B-cell receptor and its signaling pathways as very promising therapeutic targets for B-cell lymphomas.”


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