Cancer Immunotherapy

Acute myeloid leukemia (AML) is an aggressive blood cancer caused by overgrowth of immature blood cells in the bone marrow (BM). In 2020, around twenty thousand people will be diagnosed with AML in the US and the vast majority will die within a year of diagnosis. Approximately 25% of all AML patients harbor a mutation called isocitrate dehydrogenase (IDH). This gives AML cells the abnormal ability to produce an oncometabolite called, R-2-hydroxyglutarate (R-2-HG), blocking maturations of the cancer cells.

Using IDH mutant AML as an example to explore immune dysregulation in myeloid malignancies, we aim to: 1) characterize how the different subtypes of immune cells are quantitative and qualitatively affected at various stages of myeloid malignancy development; 2) determine if IDH mutant AML blasts (cancer cells) develop because of their ability to ‘immune escape’ via expression of immune checkpoints under the influence of the oncometabolite, R-2-HG; 3) explore how various cellular component of the BM microenvironment contributes to malignant hematopoiesis in general.