Mayo Clinic announces genetically engineered model of multiple myeloma progression

The first successful model able to mimic the genetic properties of multiple myeloma (MM) has been presented by Mayo Clinic researchers. The new model, announced in the February 2008 edition of Cancer Cell magazine, is expected to speed development of more effective treatments for myeloma.

"This model helps us understand the genetic properties that lead to multiple myeloma and provides a framework for developing better therapies," said Leif Bergsagel, M.D., a Mayo Clinic physician and lead investigator for the study. "We will now be able to test new treatments on models."

Multiple myeloma is the second most common form of blood cancer after lymphoma, with 15,000 new reported cases per year. It affects the bone marrow cells, called plasma cells, which produce antibodies. MM eventually leads to destruction of bone marrow and painful osteoporosis — an important indicator that malignant cancer is present.

Myeloma is typically preceded by the development of a benign tumor called MGUS (monoclonal gammopathy of undetermined significance). MGUS is the most common lymphoid tumor in humans, and develops in an estimated 3 percent of all individuals over age 50.

In a small percentage of patients, the harmless MGUS progresses to a fully malignant cancer. The agent of change is a cancer-causing gene known as MYC, first identified 25 years ago and suspected of involvement in MM. Dr. Bergsagel and his team proved conclusively that MYC is positively linked to converting MGUS into myeloma.

"We've proven that MYC can cause the conversion," he notes. "Now we can move forward and target new therapies to prevent that from happening."

The genetically engineered mouse model is a critical step in moving researchers past the "one size fits all" approach to treating MM, and into the realm of understanding the specific development of the disease. Until this project, previous efforts to produce models able to simultaneously repeat the precise timing, tissue specificity and nature of oncogenic events had failed.

"Some aspects of the progression of myeloma are due to the acquisition of genetic mutations over time," said Dr. Bergsagel. "With this model we can identify those mutations more quickly, and better understand what's happening with the patient."

The successful development of the mouse model is the end result of six years of research for Dr. Bergsagel, a pioneer of myeloma genetics and an internationally recognized authority on the genetic roots of the disease. Also participating in the project were Marta Chesi, Ph.D., of Mayo Clinic Cancer Center, and 12 others.