Mixed Lineage Leukaemia (MLL) is a very aggressive blood cancer and commonly diagnosed in children. Typically, MLL involves changes in DNA and represents an aggressive and drug-resistant form of leukaemia. How MLL leukaemic stem cells (LSC) develop resistance to therapy is unknown, although common mechanisms implicated are the manipulation of DNA damage and the ability to evade the cell’s normal growth controls.
Dr Esposito will study a protein called PP2A, an important mediator of response to DNA damage and cell growth control, found to be inactivated in MLL. PP2A activity can be restored by a number of drugs already available for clinical use. The overall objective of this study is to understand the role of PP2A on mechanisms of drug resistance of MLL and to design novel targeted treatment approaches.