STAT3 Signaling Profiles Predict Response to Chemotherapy in Pediatric AML
Children with acute myeloid leukemia (AML) suffer through very difficult chemotherapy treatment, and still about 40% will have their disease come back. Once this happens, chemotherapy usually does not work. The biggest obstacle to improving the outlook for these patients, therefore, is our limited understanding of chemotherapy resistance.
The ultimate goal of the Redell lab is to identify the mechanisms by which AML cells withstand chemotherapy, and by disabling those mechanisms, to achieve a meaningful advance in AML treatment. We have found that some cases of AML respond to survival signals from their environment normally, but most do not. Children whose leukemia cells do not respond normally have a lower chance of survival. Therefore, we are interested in understanding why most cases do not show normal responses to environmental stimuli. We also want to understand what other processes those leukemia cells use to promote their survival, even in the face of strong chemotherapy. In this grant application, we describe experiments that will define the relationship between the way a leukemia cell responds to environmental stimuli and the way it responds to chemotherapy. We describe other experiments that will investigate differences between leukemia cells that respond to those stimuli normally and those that do not, in terms of how certain proteins are organized and which genes are expressed. Once we understand how chemotherapy resistance happens, we will be in a better position to stop it.
"I am so grateful for this Springboard award. It will provide the critical funding that my lab needs to generate new preliminary data to support an even more competitive R01 application." ~ Michele Redell, M.D./Ph.D.
Update 2014: Dr. Redell has since won a competetive NIH R01 grant to continue this work!