Project 466861

My proposed research involves looking at the interleukin-23/interleukin-23 receptor (IL-23/IL-23R) pathway in the context of acute myeloid leukemia (AML). Preliminary data for this project indicates a dependency on IL-23R by various AML cell lines. By genetically modifying these cell lines and making them incapable of producing IL-23R, we see a reduction in AML cell growth and viability. Additionally, when looking at the expression of IL-23R in primary AML patient samples, we see an increased expression of IL-23R compared to normal peripheral blood stem cells. Exploring this pathway further may prove beneficial in discovering a novel therapeutic target for the treatment of AML. Specifically, I plan to get a better understanding of IL-23 and IL-23R expression in primary AML and normal hematopoietic cells. Preliminary data shows that there appears to be a unique expression and localization pattern in our AML cell lines compared to what has been previously described in the literature for other diseases. Expanding our analysis on primary AML samples can benefit our understanding of this pathway and find potential correlations between expression and known molecular subtypes of AML.Secondly, due to the reductions in cell growth and viability of our AML cell lines when genetically modifying IL-23R, I plan to look at potential methods of pharmacological inhibition against this pathway as it may prove beneficial in discovering a novel therapy for AML. Lastly, it was seen in our data that AML cell lines and patient samples had a unique expression and localization of IL-23R. This has not been previously described in current literature. I plan on studying this signalling pathway within AML by studying the cytokine and by looking for AML IL-23R binding partners.