Figure 2.

Mechanisms of leukemogenesis in FLT3-ITD/TKD-mutated acute myeloid leukemia. Constitutive activation of the FLT3 receptor results in downstream signaling pathway activation promoting cell proliferation and survival. Resistance to FLT3 inhibitor therapy can occur via both primary and secondary resistance mechanisms (A). Mechanisms of leukemogenesis in IDH-mutated acute myeloid leukemia. Production of the oncometabolite 2-hydroxyglutarate results in epigenetic reprogramming and altered cellular metabolism. As with resistance to FLT3 inhibitors, both primary and secondary resistance mechanisms have been described to IDH inhibitors (B).