Researchers Find Genetic Target for Deadly Lymphoma Subtype

Wilmot Director Part of Study that Opens New Doors for Therapy

Richard I. Fisher, M.D.

Richard I. Fisher, M.D.

Richard I. Fisher, M.D., director of the James P. Wilmot Cancer Center at the University of Rochester Medical Center, has co-authored a study in which scientists have discovered a new gene mutation that drives activated B cell lymphoma. The study, published in the journal Nature, says that the discovery could provide a new route to attempt to stop the dangerous genetic activity.

“This opens the door for targeted therapy that may not cause the type of general toxicity we usually see with chemotherapy,” said Fisher, who is also deputy group chair of the Southwest Oncology Group (SWOG), a group of the top cancer researchers in the United States which has a special interest and expertise in lymphoma.

A consortium of scientists from around the world, including SWOG, and led by a laboratory from the Metabolism Branch of the National Cancer Institute in Bethesda, Md., used advanced gene sequencing techniques to uncover the MYD88 mutations in the least curable form of lymphoma, known as ABC subtype (activated B cell). Remarkably, MYD88 mutations were observed in 29 percent of biopsy samples involved in the study, while the mutation was rare or absent in other subtypes of lymphoma. This established MYD88 as among the most frequently altered genes in this malignancy. 

ABC lymphoma is a common type of diffuse large B cell lymphoma. The ability of ABC malignant cells to survive, despite treatment with chemotherapy and a newer drug, Rituximab, results in less than a 40 percent cure rate for this particular subtype.  Scientists identified the MYD88 signaling pathways integral to the development of ABC lymphoma, and learned that MYD88 coordinates a signaling “tower” consisting of various members of other important families of genes.

The study demonstrated what is required at the cellular level to maintain the viability of ABC cancer cells. Conversely, by identifying the location of the mutation that is apparently unique to ABC, researchers believe they also located an enticing target for treatment, and perhaps a better way to genetically identify which patients might respond to a different combination of therapies.

Corresponding author is Louis M.  Staudt, M.D., Ph.D., at the Metabolism Branch, Center for Cancer Research, National Cancer Institute.

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