CLL: Identifying what causes therapy resistance What is this research looking at? Chronic lymphocytic leukaemia (CLL) is a common malignancy of B cells, the antibody-producing cells in the blood. Although therapies are available to treat this condition, none are curative, and many patients develop resistance and suffer relapse. Importantly, relapse is often accompanied by an increase in the aggressive behaviour of tumours. The mechanism through which CLL cells adapt to therapies is beginning to be understood. Genetic studies show this involves selection of particular malignant cell sub-types. However, why selected cells behave in a more aggressive way is unknown. We hypothesise that this behaviour is the result of changes in the way cells signal within themselves. We propose to identify proteins involved in generating and propagating these signals, known as kinases, and assemble them into networks to gain insight into how signalling changes during development of therapy resistance. What could this mean for people affected by leukaemia? This research has the potential to discover new mechanisms that could be used to design new therapies or modify existing ones to improve patient outcomes. Official project title: Kinomic reprogramming during clonal evolution and therapy resistance in chronic lymphocytic leukaemia.