A novel compound for treatment of T cell leukemia
"Without ALSF's support we would not even be close to this discovery. Now because of your funds we are publishing the findings in Blood. The technician I was able to hire is absolutely fabulous and continues to make very nice progress on target identification." - Nikolaus Trede, MD/PhD, Huntsman Cancer Institute
Initial Project Goal:
Acute lymphocytic leukemia (ALL) is the most common cancer of childhood. This disease is caused by uncontrolled growth of immature white blood cells, called lymphocytes. One particular subtype of ALL is caused by immature T lymphocytes (T-ALL). While leukemia of childhood has become more treatable, two principal problems remain: 1) T-ALL is still difficult to treat, requiring higher doses of chemotherapy, and fewer T-ALL patients remain disease-free. 2) Chemotherapy drugs used against leukemia also affect all other body cells. These unwanted side effects include short stature, infertility, learning deficits, heart disease, and secondary cancers. Hence, discovering new treatments that target T lymphocytes efficiently without causing side effects is crucial. These new treatments need first be identified and tried in animal models before they can be used in humans.
Zebrafish are small vertebrates that have been used successfully as animal models for human diseases. We have previously generated a special line of zebrafish, where all T lymphocytes are green fluorescent allowing us to detect differences in T lymphocyte numbers under the microscope. Thus we can directly monitor the effect of a large number of new drugs on T cell survival. After screening 39,200 chemical molecules we identified Compound 3 with particularly promising characteristics. C3 specifically kills all human T-ALL cells tested and is not toxic to mice. We now propose to carry out experiments to develop C3 into a new, targeted treatment for T-ALL that will benefit children and adults afflicted with this dangerous disease without incurring debilitating side effects.