Effects of menin inhibitors and Isocitrate dehydrogenase (IDH) inhibitors on dendritic cells (DCs)
The project of Tizian Kaiser investigates the effect of menin inhibitors (revumenib, bleximenib) and IDH inhibitors (ivosidenib, olutasidenib, enasidenib) on dendritic cells (DCs). Menin inhibitors are currently investigated in clinical trials for acute myeloid leukemia (AML) patients with KMT2A rearrangements or NPM1 mutations. IDH inhibitors are approved for patients with relapse or refractory IDH-mutated AML. AML is a disease of the hematopoietic system caused by genetic alterations leading to cytopenia, immunosuppression with an increased incidence of infections and impaired blood coagulation. Without treatment, AML is lethal. DCs coordinate and induce antigen specific adaptive immunity. The first aim of the project is to dissect the impact of menin and IDH inhibitors on DC viability, differentiation and activation. The second aim is to decipher the impact of these inhibitors on critical functions of DCs such as antigen uptake, cytokine production, migration and T cell induction. The third aim is to elaborate their modes of action to alter DC differentiation/activation and their critical functions with western blot or RNA sequencing.