Researchers say they have developed an animal model that allows them to better understand the mechanisms leading to multiple myeloma (MM) and other plasma cell neoplasms.
The group described this model in Scientific Reports.
“So far, there have not been animal models of malignant plasma cell diseases that allow us to study their stepwise progression and fully understand the complex cellular mechanisms,” said study author Stephen D. Nimer, MD, of the Sylvester Comprehensive Cancer Center at the University of Miami in Florida.
“Now that we have a proper model of the disease, we’ll be able to more effectively study multiple myeloma as well as potential treatments.”
To create this model, the researchers crossed 2 genetically modified mice: mice lacking the Mef gene and mice with a Rad50 gene mutation (Rad50s).
Mef, also called Elf4, is a transcription factor known to both promote and suppress cancer formation. Rad50 is a component of a sensor of DNA damage induced by various stresses, and it regulates the DNA damage response pathways in cells.
The researchers found that Mef−/−Rad50s/s mice initially had abnormal plasma cell proliferation and monoclonal protein production.
Then, they developed anemia and a decreased bone mineral density. And 70% of these mice died from MM or other plasma cell neoplasms.
“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,” said study author Takashi Asai, MD, PhD, also of the Sylvester Comprehensive Cancer Center.
Considering their findings together, the researchers said this model recapitulates the systemic manifestations of human MM and other plasma cell neoplasms. And their work suggests the Rad50s and Mef/Elf4 pathways cooperate to initiate myelomagenic mutations that promote plasma cell transformation.
“Although outcomes for multiple myeloma patients have greatly improved, it remains an incurable disease, despite the availability of newer treatments,” Dr Nimer noted.
“Several animal models of multiple myeloma have been reported, including models of human myeloma cells. However, these models imperfectly mimic the human disease. Developing more reliable and accurate animal models that help us better understand myeloma and test new treatments will take us to the next level on the long and challenging road to a cure.”
