Richard S. Houlston, M.D., Ph.D. Institute of Cancer Research (United Kindom)

THERAPY/ PROGNOSTIC

Identification of Germline Variants Influencing the Clinical Expression of Chronic Lymphocytic Leukemia

Update:

We are conducting a genome-wide scan of single nucleotide polymorphisms (SNPs) to identify variants influencing the clinical behaviour of CLL. To generate unbiased findings, we are evaluating the genetic makeup of 10,000 SNPs DNAs from patients entered into a large phase three trial, CLL4. CLL4 is the most comprehensive trial thus far conducted in the UK and incorporates several important elements in addition to establishing the possible benefits of the purine analogue flurdarabine used alone or in combination with cyclophosphamide as a first-line treatment for patients. In addition to examining the relationship between genotype and overall survival the analysis will allow us to examine the relationship between genotype and progression free survival, time to progression, and toxicity.

Progress has been in line with that anticipated. To date we have completed all genotyping and are engaged in relevant statistical analyses. Any associates between genotype and clinical outcome will be validated through collaborations with other researchers engaged in similar work. To this end we have already established collaborations with two research groups who have access to large datasets. Ultimately, it will be highly desirable to establish the biological basis of any significant associations.