Dissecting the role and mechanism of MLLT10 fusion proteins to treat pediatric leukemia
Children with certain types of leukemia have a specific genetic mutation where a gene called MLLT10 gets scrambled and fused with other genes. This mix-up disrupts how genes are normally turned on and off, causing abnormal cell growth and leukemia. These leukemias are difficult to treat. Many research teams are studying how this MLLT10 fusion works to cause leukemia. Two key features of the scrambled genes have been discovered: 1) a part of the fusion gene that sticks to important machinery for gene control, and 2) a flexible, floppy region that might be helping to build abnormal structures inside cells. These abnormal structures might further mess up gene control. We want to understand this process better and use this knowledge to develop new treatments for aggressive childhood leukemia. Their plan has two parts: 1) figure out how to break apart these scrambled genes and restore normal gene function, and 2) develop drugs targeting the cancer cells with this MLLT10 fusion like a sniper taking out only the cancer cells.
Project Goal
We aim to understand how a specific genetic defect (MLLT10 fusion) causes a tough type of childhood leukemia. Specifically, we aim to figure out how the faulty gene works. We will look at how it affects the methylation of histones, which can turn genes on or off. We will also see how the faulty gene affects the creation of proteins from instructions in genes. Finally, we will test a harmless version of the faulty gene to see if it still causes leukemia, helping them understand which part (histone methylation or protein creation) is more important. Part 2: Developing new treatments. We will study the flexible part of the faulty gene to see if it helps build abnormal structures. If so, they'll try to develop ways to disrupt these structures, potentially stopping the faulty gene from causing leukemia. They're also looking at unique features of the faulty gene to design medications that target only cancer cells with this defect, leaving healthy cells unharmed. By understanding how the faulty gene works and developing ways to target it, we hope to create new treatments for this aggressive childhood leukemia.
