title: Molecular pathogenesis of AML: translating insights to the clinic.
abstract: 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.
authors.affiliation: Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. Electronic address: leviner@mskcc.org.
authors.forename: Ross L
authors.initials: RL
authors.lastname: Levine
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D004268:DNA-Binding Proteins / Q000235:genetics*; D049308:Dioxygenases; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D051379:Mice; D009154:Mutation; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D018570:Risk Assessment; D017422:Sequence Analysis, DNA; D016019:Survival Analysis; D057170:Translational Research, Biomedical; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; C538784:IDH2 protein, human; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human; D049308:Dioxygenases; C541081:TET2 protein, human; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3
keywords: AML; DNA sequencing; FLT3; TET2; acute myeloid leukemia; murine models