title: Mutational landscape of AML with normal cytogenetics: biological and clinical implications.
abstract: Acute myeloid leukemia (AML) is a molecularly heterogeneous disease. Based on cytogenetics and FISH, AML patients are stratified into three major risk categories: favourable, intermediate and unfavourable. However, prognostic stratification and treatment decision for the intermediate risk category, that mostly comprises AML patients with normal cytogenetics (CN-AML), has been difficult due to the clinical heterogeneity and scarce knowledge of the molecular alterations underlying this large AML subgroup. During the past decade, the identification of several mutations associated with CN-AML has resulted into important advances in the AML field. In this review, we address the biological features of the main mutations associated with CN-AML and the impact of next generation sequencing studies in expanding our knowledge of the molecular landscape of CN-AML. In addition, we outline the prognostic value of mutations for risk stratification of CN-AML patients and discuss the potential of mutations discovery process for developing new molecular targeted therapies.
authors.affiliation: Institute of Hematology, University of Perugia, Perugia, Italy. mpmartelli@libero.it
authors.forename: Maria Paola
authors.initials: MP
authors.lastname: Martelli
authors.forename: Paolo
authors.initials: P
authors.lastname: Sportoletti
authors.forename: Enrico
authors.initials: E
authors.lastname: Tiacci
authors.forename: Massimo F
authors.initials: MF
authors.lastname: Martelli
authors.forename: Brunangelo
authors.initials: B
authors.lastname: Falini
mesh_terms: D014408:Biomarkers, Tumor; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics*; D020732:Cytogenetic Analysis; D015973:Gene Expression Regulation, Leukemic; D018740:Genetic Heterogeneity; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D007527:Isoenzymes / Q000235:genetics; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D000090243:Nucleophosmin; D011379:Prognosis; D018570:Risk Assessment; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D022762:CCAAT-Enhancer-Binding Proteins; C515848:CEBPA protein, human; D007527:Isoenzymes; D009687:Nuclear Proteins; D000090243:Nucleophosmin; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3