title: Clinical characterization of acute myeloid leukemia with myelodysplasia-related changes as defined by the 2008 WHO classification system.
abstract: Although some studies have validated the 2001 World Health Organization (WHO) classification of acute myeloid leukemia (AML), including the importance of multilineage dysplasia, others have suggested that multilineage dysplasia correlates with unfavorable cytogenetics but has no independent impact on prognosis. In 2008, the revised WHO classification has expanded this category into "AML with myelodysplasia-related changes" (AML-MRC). We evaluated the clinical, pathologic, cytogenetic, and molecular features of 100 AML patients using the 2008 WHO criteria. Patients underwent genetic screening for NPM1, FLT3-ITD, FLT3-D835, and CEBPA mutations. Compared with patients with AML, not otherwise specified, patients with AML-MRC were significantly older (P= .014), presented with a lower hemoglobin (P= .044), more frequently expressed CD14 (P= .048), and exhibited a decreased frequency of CEBPA mutations (P= .001). Multivariate analysis indicated that patients with AML-MRC had a significantly worse overall survival, progression-free survival, and complete response compared with AML-not otherwise specified (all P< .001). These data support the clinical, morphologic, and cytogenetic criteria for this 2008 WHO AML category.
authors.affiliation: Department of Pathology, Center for Clinical Investigation, Stanford University Medical Center, CA 94305, USA. okw@stanford.edu
authors.forename: Olga K
authors.initials: OK
authors.lastname: Weinberg
authors.forename: Mahesh
authors.initials: M
authors.lastname: Seetharam
authors.forename: Li
authors.initials: L
authors.lastname: Ren
authors.forename: Katie
authors.initials: K
authors.lastname: Seo
authors.forename: Lisa
authors.initials: L
authors.lastname: Ma
authors.forename: Jason D
authors.initials: JD
authors.lastname: Merker
authors.forename: Jason
authors.initials: J
authors.lastname: Gotlib
authors.forename: James L
authors.initials: JL
authors.lastname: Zehnder
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Arber
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics; D020732:Cytogenetic Analysis; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000145:classification* / Q000175:diagnosis / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000145:classification* / Q000175:diagnosis / Q000235:genetics / Q000401:mortality; D009687:Nuclear Proteins / Q000235:genetics; D000090243:Nucleophosmin; D012189:Retrospective Studies; D016019:Survival Analysis; D014944:World Health Organization; D055815:Young Adult; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; C515848:CEBPA protein, human; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3