The Role of Somatic Mutations in Acute Myeloid Leukemia Pathogenesis

Acute myeloid leukemia (AML) is characterized by attenuation of lineage differentiation trajectories that results in impaired hematopoiesis and enhanced self-renewal. To date, sequencing studies have provided a rich landscape of information on the somatic mutations that contribute to AML pathogenesis. These studies show that most AML genomes harbor relatively fewer mutations, which are acquired in a stepwise manner. Our understanding of the genetic basis of leukemogenesis informs a broader understanding of what initiates and maintains the AML clone and informs the development of prognostic models and mechanism-based therapeutic strategies. Here, we explore the current knowledge of genetic and epigenetic aberrations in AML pathogenesis and how recent studies are expanding our knowledge of leukemogenesis and using this to accelerate therapeutic development for AML patients.