Promoter Hypermethylation in MLL-Rearranged Leukemias: Biology and Therapeutic Targeting
Several common childhood leukemias are now considered curable. However, there are features of leukemia cells which continue to make them difficult to treat. One such feature is having an alteration in a gene called MLL. It is not yet fully understood why MLL alterations cause leukemia. In addition, current therapies do not seem as effective against leukemia with MLL alterations as it is in those without. We hope to better understand MLL in a way that will bring about new therapies for the disease. Our own body can destroy cancer cells with the help of tumor suppressor genes. Early studies suggest that several of these tumor suppressor genes are 'turned off' in leukemia with MLL alterations. Drugs, that are well tolerated in people, are already available which may be able to turn these genes 'back on.' We propose to study a large number of leukemia samples from infants, children and adults with MLL mutations using laboratory techniques which can identify which genes might be 'turned off.' Additionally, we hope to study drugs which can reverse that process to see if they can be added to current therapies with the goal of improving the outcome of patients with MLL altered leukemias.
