Abstract 1827: Using Drosophila to study the role of metabolic enzyme mutations in glioblastoma and leukemia

Metabolic reprogramming is a common hallmark shared by nearly all proliferating cancer cells, and thus has emerged as an exciting new direction in cancer research. Many signaling pathways have been implicated in mechanisms leading to the shift of metabolic programs in tumors, but more recently a small number of metabolic enzymes have also been identified in this process. Genes encoding the metabolic enzymes Isocitrate dehydrogenase 1 (IDH1) and 2 (IDH2) were found to be mutated in up to 70% of low-grade and medium grade gliomas, and in 15-20% of adult acute leukemia samples. These findings were the first to link the IDH gene to tumorigenesis. IDH1 and IDH2 function to irreversibly catalyze the oxidative decarboxylation of isocitrate to α-ketoglutarate (α-KG). We are studying how mutations in IDH affect the metabolism and cellular processes of the cell. To this end, we have expressed IDH-R132H in Drosophila glial cells and hemoctyes to learn more about the impact of neomorphic activity of IDH in gliobastoma and chronic myeloid leukemia. We have verified that these cells now produce 2-HG, as is known in human tumors harboring IDH mutations. We have observed different cellular responses to IDH mutations in glia versus hemoctyes and have begun to investigate why this may be. Ultimately, the goal of our research is to elucidate the mechanism(s) that cause IDH to contribute to oncogenic activity in specific tissues, and use this knowledge to design tailored therapeutics. Citation Format: Julia Fabiano, Gabriela Chiaramida, Mira Magner, Meghan O'Connor, Joseph Stallone, Nicholas DiDuca, Kathryn Neville, Richard Tartarini, Marla Tipping. Using Drosophila to study the role of metabolic enzyme mutations in glioblastoma and leukemia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1827. doi:10.1158/1538-7445.AM2017-1827