Diffuse Large B Cell Lymphoma (OMIM 109565)
Chemotherapy can cure fewer than half of patients with diffuse large B cell lymphoma (DLBCL), also known as non-Hodgkin’s lymphoma. Physicians determine dosages based on a standard profile that considers age, cancer stage, number of affected sites in the body, and other factors. Using this method of classifying patients results in very high dosing for many patients whose cancers do not respond.
Under a microscope, all DLBCL cells look alike, but their gene expression patterns differ. Researchers are using this information to subtype the cancer, so that treatments can become more personalized. Specifically, they are screening for variants of 13 genes that affect B cells—such as genes that encode signaling molecules, cellular adhesion molecules, cell cycle proteins such as kinases and cyclins, oncogenes, tumor suppressors, and genes that control apoptosis (programmed cell death) and angiogenesis (ability to build a blood supply). In addition, the researchers are using DNA microarrays to track expression of 6,817 genes. If a gene is greatly over- or underexpressed in a cancerous B cell compared to a healthy B cell, then it can be used to refine diagnosis of this type of cancer.
By conducting these genetic tests on 77 people diagnosed with DLBCL by standard criteria, researchers grouped them into two broad categories. In one group, the cancerous B cells had gene expression profiles that were very similar to those of normal B cells found in lymphoid organs. These people had a 70% 5-year survival rate, and tended to respond well to standard chemotherapy. The other group had a 12% 5-year survival rate, and did not do well on chemotherapy.