Flt3-ITD-induced remodelling of non-leukaemic myeloid cells and its role in leukaemic immune escape

In P05 we will investigate how the oncogenic Flt3-ITD mutation reshapes the phenotype and function of the non-malignant myeloid compartment within the bone marrow (BM) niche to drive immune evasion in acute myeloid leukemia (AML) (Aim 1). Next, we will define the molecular mechanisms by which Flt3-ITD-driven changes in three candidate metabolites (N-acetylaspartate, lactic acid, and serine), affect resident BM macrophages (Aim 2). Furthermore, we will validate the findings from Aim 1 and 2 in AML samples from patients and novel human 3D bone marrow niche models (Aim 3).