title: Role of genotype-based approach in the clinical management of adult acute myeloid leukemia with normal cytogenetics.
abstract: Acute myeloid leukemia (AML) is the most common form of acute leukemia affecting adults. Although it is a complex disease driven by numerous genetic and epigenetic abnormalities, nearly 50% of patients exhibit a normal karyotype (CN-AML) with an intermediate cytogenetic risk. However, a widespread genomic analysis has recently shown the recurrence of genomic aberrations in this category (mutations of FLT3, CEBPA, NPM1, RUNX1, TET2, IDH1/2, DNMT3A, ASXL1, MLL and WT1) thus revealing its marked genomic heterogeneity. In this perspective, a global gene expression analysis of AML patients provides an independent prognostic marker to categorize each patient into clinic-pathologic subgroups based on its molecular genetic defects. Consistently such classification, taking into account the uniqueness of each AML patient, furnishes an individualized treatment approach leading a step closer to personalized medicine. Overall the genome-wide analysis of AML patients, by providing novel insights into biology of this tumor, furnishes accurate prognostic markers as well as useful tools for selecting the most appropriate treatment option. Moreover it provides novel therapeutic targets useful to enhance efficacy of the current anti-AML therapeutics. Here we describe the prognostic relevance of such new genetic data and discuss how this approach can be used to improve survival and treatment of AML patients.
authors.affiliation: Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; Department of Hematology and Oncology, I.R.C.C.S. A.O.U. San Martino-IST, Genoa, Italy. Electronic address: antonia_cagnetta@dfci.harvard.edu.
authors.forename: Antonia
authors.initials: A
authors.lastname: Cagnetta
authors.affiliation: Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
authors.forename: Sophia
authors.initials: S
authors.lastname: Adamia
authors.affiliation: Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
authors.forename: Chirag
authors.initials: C
authors.lastname: Acharya
authors.affiliation: Department of Hematology and Oncology, I.R.C.C.S. A.O.U. San Martino-IST, Genoa, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Patrone
authors.affiliation: Department of Hematology and Oncology, I.R.C.C.S. A.O.U. San Martino-IST, Genoa, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Miglino
authors.affiliation: Department of Hematology and Oncology, I.R.C.C.S. A.O.U. San Martino-IST, Genoa, Italy.
authors.forename: Alessio
authors.initials: A
authors.lastname: Nencioni
authors.affiliation: Department of Hematology and Oncology, I.R.C.C.S. A.O.U. San Martino-IST, Genoa, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Gobbi
authors.affiliation: Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; Department of Hematology and Oncology, I.R.C.C.S. A.O.U. San Martino-IST, Genoa, Italy. Electronic address: michele_cea@dfci.harvard.edu.
authors.forename: Michele
authors.initials: M
authors.lastname: Cea
mesh_terms: D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics; D000090205:DNA Methyltransferase 3A; D004268:DNA-Binding Proteins / Q000235:genetics; D049308:Dioxygenases; D005838:Genotype; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000401:mortality / Q000628:therapy*; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D000090243:Nucleophosmin; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics; D025721:WT1 Proteins / Q000235:genetics; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; C515848:CEBPA protein, human; D004268:DNA-Binding Proteins; C000717967:DNMT3A protein, human; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D025721:WT1 Proteins; C583751:WT1 protein, human; D000090243:Nucleophosmin; D049308:Dioxygenases; C541081:TET2 protein, human; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3
keywords: AML; Genomic heterogeneity; Minimal residual disease; Mutations; Prognosis