Sir Mortimer B. Davis-Jewish General Hospital
STAT6 mutations in relapsed/refractory diffuse large B cell lymphoma
Lymphoma is a cancer of the lymphocytes that can be treated with chemotherapy, but is often fatal once resistance develops. We profiled mutations in one type of relapsed lymphoma, diffuse large B cell lymphoma (DLBCL). Here we found that the protein STAT6 is more frequently mutated in relapsed samples than those taken when the disease is first diagnosed. STAT6 is a protein that binds DNA and controls genes important in lymphocyte survival. In our preliminary experiments, we found that cells with these mutations grow faster. This has led us to try to understand how mutated STAT6 leads to increased cancer cell growth. We will then test whether cells with the mutant STAT6 protein relapse more quickly following treatment with chemotherapy. Furthermore, we think that these tumors may respond to a new class of drugs targeting this pathway alone or in combination with chemotherapy. We believe that this mutant STAT6 protein is a marker for tumors who will not response well to chemotherapy, but also a marker for those tumors that might respond to these STAT6-targeted therapies.