Novel Disease Model May Improve Treatment of Multiple Myeloma

A newly developed animal model helped researchers gain a better understanding of the underlying mechanisms that lead to the development of multiple myeloma.

For the study, published in Scientific Reports, researchers generated a new animal model by crossing 2 types of genetically modified mice: mice that lacked the Mef gene (or Elf4) and mice with a Rad50 gene mutation (Rad50s).

Elf4, a transcription factor that was originally cloned in the laboratory, is known to help promote and suppress the formation of cancers. Rad50 is a DNA repair protein that regulates the DNA damage response pathways in cells.

“Multiple myeloma is the second most common hematologic malignancy in the US and it is a very complex disease,” said senior study author Stephen D. Nimer, MD. “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. 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.”

The results of the study showed that 70% of the generated mice died from either multiple myeloma or other plasma-cell neoplasms with various symptoms related to multiple myeloma.

“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 first study author Takashi Asai, MD, PhD.

Although prior research has used animal models, the information has been unreliable and inaccurate. However, this newly developed model will allow researchers to gain a better insight into the development of multiple myeloma.

“Although outcomes for multiple myeloma patients have greatly improved, it remains an incurable disease, despite the availability of newer treatments,” Nimer said. “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.”