Figure 3.

Mechanisms of leukemogenesis in AML with mutated NPM1 gene. NPM1 mutations alone are not sufficient for causing leukemia. They arise from common progenitor cells (CMP) that have expanded following clonal hematopoiesis. This figure shows the most common combination of mutations, but other mutations causing clonal hematopoiesis could provide a similar background. NPM1 mutations are leukemia-initiating. They disrupt multiple mechanisms with a specific dependence on HOX genes and their DNA-binding cofactor MIES1.