The Clinical Utility of Genetic Risk Scores in Chronic Lymphocytic Leukemia

Susan L. Slager, PhD, endowed professor of lymphoma research at Mayo Clinic, discusses the background of her research on inherited germline genetics for risk of chronic lymphocytic leukemia (CLL).

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0:09 | I am looking at the inherited germline genetics for risk of chronic lymphocytic leukemia. We and others have identified over 42 inherited variants that are associated with risk of getting CLL, and these inherited variants are distributed across the genome. They are not located in any particular region, but each of these inherited variants have a small effect on your risk of disease of getting CLL. We looked at combining these inherited variants into a score, a polygenic risk score, to see if that score is a better predictor of risk of getting chronic lymphocytic leukemia.

0:48 | What we found is that score is a robust predictor, and we have been able to validate it so that individuals who have a large number of inherited variants have a 3-and-a-half-fold increased risk of getting CLL, and if you have a family history of CLL or lymphoma in general, we are finding that this this score is increases your risk of about 7-and-a-half-fold for risk of getting CLL. If you are on a low end, so if you have a low inherited number of these variants, your score is protective for risk of getting CLL.

1:24 | We also screened individuals for monoclonal B-cell lymphocytosis, or which is the precursor to CLL. We wanted to see if this score would also help predict individuals with this precursor condition if they progress to having chronic lymphocytic leukemia. This precursor condition is very common in the population, especially over the age of 40, but not everybody progresses to CLL. So, can this genetic risk score predict who will progress to getting CLL? We are finding that there is evidence that the score also helps us identify which individuals will progress to CLL, but more research is needed.