This week I can describe our current research focused on lymphoid cancer in British Columbia.

Building on the insight we had gained in the 1980s and 1990s into why lymphoid cancers develop and how they respond to treatment, we turned our attention to the basic molecular biology of these diseases. Lymphoid cancers are unique among human cancers in several aspects. In lymphoid cancer the cells which turn malignant are lymphocytes, the white blood cells of which our immune system is composed. Our immune system lymphocytes face a unique challenge compared to most cells in our body. They must proliferate (give rise to new lymphocytes) enormously in response to invading germs and they must be capable of recognizing these germs with extreme accuracy.

To meet these challenges, first, lymphocytes must have a “hair trigger” to begin multiplying by the billions in just a matter of hours. Second, lymphocytes must tinker with and redesign their own genetic code so that they can make highly specific antibodies (immunoglobulins) that recognize specific germs, for example, influenza, and targeted killer cells that can identify other cells in the body that have been invaded by germs, for example, tuberculosis. No other cells in the body are permitted to proliferate so enormously or allowed to redesign their own basic cellular structure. When these unique processes go wrong, the defective lymphocytes give rise to lymphoid cancers, lymphoma, myeloma and lymphocytic leukemia.

My research group concentrates on understanding the underlying genetic instructions that cause lymphoid cancers. We have described previously unknown errors in the genetic code of lymphocytes that transform normal lymphocytes into malignant ones. Sometimes these changes are mutations in a specific gene.

For example, we were able to demonstrate that mutations in a gene called EZH2 are present in more than 80 per cent of lymphomas derived from antibody-making lymphocytes. In other experiments, we have shown that cytogenetic re-arrangements (breakage and movement of pieces of chromosomes from their normal location to abnormal locations on other chromosomes) can move the master regulator of cell proliferation, the MYC gene, to a new chromosomal location where it is turned on all the time rather than on and off when needed. It can also move the controller of programmed cell death, the BCL2 gene, which the immune system uses to produce the precisely targeted immune response we need to fight individual infections. Re-arrangements of MYC and BCL2 cause particularly aggressive types of lymphoma.

How are we able to make these exciting discoveries in lymphoid cancer? By combining the support we receive from granting agencies such as the Terry Fox Foundation and Genome BC with the funding donated by individual donors through the BC Cancer Foundation. Those funds from the Foundation are particularly important because they allow our research team to choose promising approaches on short notice nimbly taking advantage of new, sometimes previously undiscovered, opportunities. We could not have accomplished the research that has kept us among the elite lymphoid cancer researcher groups around the world without that support.

Thanks for reading,

Dr. Connors 

Medical oncologist and Clinical Director, Centre for Lymphoid Cancers, BC Cancer