Molecular pathogenesis of AML: translating insights to the clinic

Specific combinations of mutations, including FLT3 and IDH1/IDH2/TET2, frequently co-occur in acute myeloid leukemia (AML) and are associated with poor prognosis. These mutation combinations can be modeled in mice to provide a more genetically accurate model of AML. Within these models, stem cells may be different depending on how experiments are conducted and based on context. No one mutation can turn on a gene; rather the perfect storm of the right genes in the right cell is necessary to produce AML. Furthermore, this understanding is therapeutically relevant. Rapid and accurate targeted DNA sequencing will identify mutations of prognostic and therapeutic significance and will guide treatment choices in the future.