Scientists report that they have determined which lymphomas are controlled by the BCL6 gene. A team of researchers from Albert Einstein College of Medicine and Dana-Farber Cancer Institute in Boston hope they will be able use this information to select patients who will be most responsive to a novel targeted treatment called BPI. In lab tests, this therapy showed to inhibit BCL6 and kill lymphoma cells.
The researchers will report the results of their research, funded by The Leukemia & Lymphoma Society, in the February 20 online issue of the journal Proceedings of the National Academy of Sciences.
Since not all forms of lymphoma are associated with BCL6, the researchers, led by Ari Melnick, M.D., of Albert Einstein, and Margaret Shipp, M.D., of Dana-Farber, identified which lymphomas have the BCL6-controlled gene signature. They found a set of 485 BCL6-controlled genes. The team then confirmed that all lymphomas with BCL6 signatures are killed by BPI while lymphomas without the signature are resistant. This success in the laboratory will allow the selection of the lymphoma patients most likely to respond to this treatment for clinical trials of BPI-BCL6 targeted therapy.
Also funded by The Leukemia & Lymphoma Society, researchers at H. Lee Moffitt Comprehensive Cancer Center in Tampa, led by William Kerr, Ph.D., have discovered that the SHIP gene plays a critical role in graft vs. host disease (GvHD), in which a donor's immune cells (the graft) attack a stem cell transplant patient's healthy tissue (the host) besides just the cancer cells.
By using genetically engineered mice, the researchers have shown that inactivating the SHIP gene for just one week protects transplant recipients from acute GvHD. This protection is seen even when the graft contains extra immune cells to help the graft take or when the graft cells are completely mismatched to the recipient.
The findings will be published in the March 1st issue of the Journal of Immunology.
Since the SHIP gene is also present in humans, Dr. Kerr says the team's findings are important for cancer patients. "If we can identify approaches to inhibit SHIP in patients, then we could potentially reduce the risk of GvHD in matched transplants that are currently used to treat blood cancer patients, perform allogeneic transplants even when a matched donor cannot be found, and increase the number of donor immune cells that can be given to patients post-transplant to combat cancer relapse.”