Visualising molecular messengers in chronic lymphocytic leukaemia

There are around 440,000 new cases of leukaemia diagnosed worldwide each year and around a quarter of these are a type called chronic lymphocytic leukaemia (CLL). CLL is a cancer of a type of white blood called a B-lymphocyte. The surfaces of B-lymphocytes are coated with unique proteins called “B-cell receptors”, which act as messengers, carrying molecular information from the outside of the cell to the inside. Once inside, the molecular message instructs the cell what to do by activating or deactivating genes. In CLL, the B-cell receptors are overactive causing uncontrolled growth and division of the lymphocytes. 

Blocking the molecular signals transmitted into the cell from B-cell receptors is a promising therapeutic strategy for treating CLL patients, but the drugs that have designed to do this don’t work for every patient and can have unwanted side effects. Dr Massimo Degano, based at Fondazione Centro San Raffaele in Milan, is studying the varied molecular structures of B-cell receptors to understand why this is the case. 

Using sophisticated chemical techniques, the team will work out the 3-dimensional structure of the different types of B-cell receptor, before using this information to identify drugs that can interact with the B-cell receptor and stop it working in CLL.