title: Multilineage dysplasia has no impact on biologic, clinicopathologic, and prognostic features of AML with mutated nucleophosmin (NPM1).
abstract: NPM1-mutated acute myeloid leukemia (AML) is a provisional entity in the 2008 World Health Organization (WHO) classification of myeloid neoplasms. The significance of multilineage dysplasia (MLD) in NPM1-mutated AML is unclear. Thus, in the 2008 WHO classification, NPM1-mutated AML with MLD is classified as AML with myelodysplasia (MD)-related changes (MRCs). We evaluated morphologically 318 NPM1-mutated AML patients and found MLD in 23.3%. Except for a male predominance and a lower fms-related tyrosine kinase 3-internal tandem duplication (FLT3-ITD) incidence in the MLD(+) group, no differences were observed in age, sex, cytogenetics, and FLT3--tyrosine kinase domain between NPM1-mutated AML with and without MLD. NPM1-mutated AML with and without MLD showed overlapping immunophenotype (CD34 negativity) and gene expression profile (CD34 down-regulation, HOX genes up-regulation). Moreover, overall and event-free survival did not differ among NPM1-mutated AML patients independently of whether they were MLD(+) or MLD(-), the NPM1-mutated/FLT3-ITD negative genotype showing the better prognosis. Lack of MLD impact on survival was confirmed by multivariate analysis that highlighted FLT3-ITD as the only significant prognostic parameter in NPM1-mutated AML. Our findings indicate that NPM1 mutations rather than MLD dictate the distinctive features of NPM1-mutated AML. Thus, irrespective of MLD, NPM1-mutated AML represents one disease entity clearly distinct from AML with MRCs.
authors.affiliation: Institute of Hematology, University of Perugia, Perugia, Italy. faliniem@unipg.it
authors.forename: Brunangelo
authors.initials: B
authors.lastname: Falini
authors.forename: Katja
authors.initials: K
authors.lastname: Macijewski
authors.forename: Tamara
authors.initials: T
authors.lastname: Weiss
authors.forename: Ulrike
authors.initials: U
authors.lastname: Bacher
authors.forename: Susanne
authors.initials: S
authors.lastname: Schnittger
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kern
authors.forename: Alexander
authors.initials: A
authors.lastname: Kohlmann
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Klein
authors.forename: Marco
authors.initials: M
authors.lastname: Vignetti
authors.forename: Alfonso
authors.initials: A
authors.lastname: Piciocchi
authors.forename: Paola
authors.initials: P
authors.lastname: Fazi
authors.forename: Maria Paola
authors.initials: MP
authors.lastname: Martelli
authors.forename: Antonella
authors.initials: A
authors.lastname: Vitale
authors.forename: Stefano
authors.initials: S
authors.lastname: Pileri
authors.forename: Miriam
authors.initials: M
authors.lastname: Miesner
authors.forename: Antonella
authors.initials: A
authors.lastname: Santucci
authors.forename: Claudia
authors.initials: C
authors.lastname: Haferlach
authors.forename: Franco
authors.initials: F
authors.lastname: Mandelli
authors.forename: Torsten
authors.initials: T
authors.lastname: Haferlach
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D019070:Cell Lineage; D005260:Female; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000473:pathology; D008297:Male; D009154:Mutation / Q000235:genetics*; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics*; D000090243:Nucleophosmin; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D015996:Survival Rate; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin; D051941:fms-Like Tyrosine Kinase 3