Multiple myeloma affects more than 30,000 Americans each year and is slightly more prevalent in men than in women. While considered incurable, multiple myeloma is treatable and the five-year survival rate is approximately 47 percent.
In patients with multiple myeloma, abnormal plasma cells accumulate in the bone marrow where they interfere with the production of normal blood cells. Multiple myeloma can also lead to kidney failure, bone destruction, and a predisposition for infection.
The new animal model of multiple myeloma was generated when a team of researchers crossed two genetically modified mice: mice lacking the Mef gene and mice with a Rad50 gene mutation (Rad50s). Mef, also called Elf4, is a transcription factor -- originally cloned in the Nimer lab -- that is known to both promote and suppress the formation of cancers. Rad50 is a component of a sensor of DNA damage induced by various stresses and it regulates the DNA damage response pathways in cells.
Researchers find that 70% of Mef−/−Rad50s/s mice die from multiple myeloma or other plasma cell neoplasms. These mice initially show an abnormal plasma cell proliferation and monoclonal protein production, and then develop anemia and a decreased bone mineral density.
Tumor cells can be serially transplanted and the pathogenesis of plasma cell neoplasms in these mice is not linked to activation of a specific oncogene, or inactivation of a specific tumor suppressor. This model recapitulates the systemic manifestations of human plasma cell neoplasms, and implicates cooperativity between the Rad50s and Mef/Elf4 pathways in initiating myelomagenic mutations that promote plasma cell transformation.
"In this study, we found that 70 percent of the generated mice died from multiple myeloma or other plasma-cell neoplasms with various symptoms related to multiple myeloma," said first author of the study. "We also found that the phenotype of these mice is not linked to activation of a specific oncogene, or inactivation of a specific tumor suppressor, other than Mef."
Novel disease model to study multiple myeloma
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