Predicting how people with CLL will respond to new BCR inhibitors

Lead researcher - Dr Francesco Forconi, University of Southampton
The influence of altered genetics on B-cell receptor levels and function in CLL
Amount awarded: £194,420
Award start date: 01 Jan 2015
Award duration: 3 years

The BCR is the molecule that defines any B-cell. Its variable characteristics determine survival in CLL patients. However there are genetic alterations that also change survival in CLL patients. We were among the first to define the prognostic significance of either BCR or new genetic alterations in CLL. However we do not know how genetic alterations and BCR activity link together. Understanding how genetic alterations affect BCR activity is extremely important now, because there are novel drugs inhibiting the function of BCR (‘BCR-inhibitors’) that are very successful, but they are effective if the BCR is active. We now wish to understand how defined genetic alterations change activity of the BCR. We will address this question in 3 ways: 1) investigating the correlations between genetic alterations and sIgM expression/function in a very large number of patients, including a small group treated with the new BCR-inhibitors; 2) studying how the most recurrently altered gene (NOTCH1) affects BCR activity 3) looking for alterations of all the known genes that can alter BCR activity. The results may have rapid benefit to CLL patients and lead to the identification of novel genetic markers associated with BCR activity and possibly response to the new BCR-inhibitors.