| In 2001, The Joshua Kahan Fund committed to funding a multi-year research project through The Children's Hospital of Philadelphia. Leading the "Joshua Project" is Carolyn A. Felix, M.D.
The "Joshua Project" will focus on what happens when genes become incorrectly joined together. Because these genes would not normally be linked to one another, it causes the genes to produce a certain protein that in turn causes leukemia. The objective of this work is to identify why these abnormal proteins form and to use this information to develop strategies for new therapies and diagnosis. This project has tremendous potential and will bring scientists and physicians closer to understanding what actually happens to cause leukemia in children and how to better treat youngsters who are stricken with this dreadful disease. "Joshua Project" Summary
Submitted by Carolyn A. Felix, M.D. - August, 2001
The leukemia cells in the majority of infants with leukemia contain an abnormality called a chromosomal translocation. A translocation occurs when two different chromosomes in the cell break and become joined to each other. This causes genes on two different chromosomes to become joined and, in some cases, to produce an abnormal protein. In leukemia in infants a gene on chromosome 11 called the MLL gene breaks and fuses with one of many different genes from various different chromosomes. We discovered a family of genes called SEPTINS with multiple family members that can be joined to MLL in the MLL translocations. The purpose of this work is to understand whether two MLL-Septin fusion proteins resulting from these translocations cause leukemia in the mouse and to determine how long it takes for leukemia to develop. A period of many months to onset of leukemia might suggest that additional abnormalities in addition to translocation are needed for leukemia to occur. Leukemia in infants with MLL translocations are associated with a poor outcome and are difficult to treat. It is essential to characterize the molecular abnormalities leading to leukemia to arrive at better treatments; the mouse model provides the means to study the molecular abnormalities associated with the development of leukemia before leukemia occur, which otherwise is not possible. |
