Researchers at Weill Cornell Medical College have made a discovery that offers patients hope for new treatments for an aggressive and common lymphoma. The powerful master regulatory transcription factor called Bcl6 is key to the survival of a majority of aggressive lymphomas, which arise from the B-cells of the immune system. The protein has long been considered too complex to target with a drug since it is also crucial to the healthy functioning of many immune cells in the body, not just B cells gone bad. But now, as reported in the journal Nature Immunology, researchers at Weill Cornell Medical College may have shown that it is possible to shut down Bcl6 in the cancer, known as diffuse large B-cell lymphoma (DLBCL), while not affecting its vital function in T cells and macrophages that are needed to support a healthy immune system.
“Scientists have been searching for the right answer to treat this difficult lymphoma, which, after initial treatment, can be at high risk of relapse and resistant to current therapies,” says lead investigator Ari Melnick, MD. “Believing that Bcl6 could not be targeted, some researchers have been testing alternative therapeutic approaches. This study strongly supports the notion of using Bcl6-targeting drugs.”
“When cells lose control of Bcl6, lymphomas develop in the immune system,” Melnick adds. Lymphomas are 'addicted' to Bcl6, and therefore Bcl6 inhibitors powerfully and quickly destroy lymphoma cells.”
Melnick says the discovery that a master regulatory transcription factor can be targeted offers implications beyond treating DLBCL. Recent studies by him and others have revealed that Bcl6 plays a key role in the most aggressive forms of acute leukemia, as well as certain solid tumors. Read the study abstract.