Tackling drug resistance in CLL

Lead researcher - Dr Andrew Steele, The University of Southampton
B cell receptor signalling is modified by IL-4 in chronic lymphocytic leukaemia (CLL)
Amount awarded: £182,378
Award start date: 01 Jan 2015
Award duration: 3 years

Chronic lymphocytic leukaemia (CLL) arises from B-cells, a type of blood cell. We believe CLL is driven via the B cell receptor (BCR) which is a protein on the surface of B cells which detects foreign proteins from bacteria or viruses. These proteins are called antigens. Once the BCR is bound to antigen it becomes activated and produces signals which leads to the survival and replication of the CLL cell.  However in some cases the BCR recognises proteins from our own bodies instead which are called autoantigens and which act like antigens. CLL is believed to be driven by these autoantigens. Chemotherapeutic agents which target this pathway are working extremely well for patients with CLL, however not all cells are killed by these drugs and therefore it is important to understand why this happens. Our preliminary data indicate that signals produced by T cells, another type of blood cell, are able to enhance the BCR signal following antigen activation in the laboratory and can overcome chemical inhibition of this pathway. This project aims to better understand how BCR signalling is regulated by these microenvironmental signals so that we can develop novel therapeutic strategies to treat this currently incurable disease.