title: Multilineage dysplasia as assessed by immunophenotype has no impact on clinical-biological features and outcome of NPM1-mutated acute myeloid leukemia.
abstract: The presence of multilineage dysplasia (MLD) by morphology at diagnosis in acute myeloid leukemia (AML) defines a separate subset in the World Health Organization classification with still-debated prognostic value. A major controversy concerns MLD's role in NPM1-mutated (NPM1⁺) AML, which correlates with good prognosis. We used flow cytometry (FC), an emerging technique for assessing dysplasia, to investigate MLD in NPM1⁺ AML by an immunophenotypic score (IPS), a technique previously adopted in myelodysplastic syndrome. Eighty-five intensively treated NPM1⁺ AML cases were studied. Patients were grouped according to the combination of data in maturing cell compartments. FC-assessed dysplasia showed a significant correlation with morphology-assessed dysplasia, showing the efficacy of this method in highlighting dysplasia in AML. Except for MLD, IPS did not influence any patient- or disease-related characteristics at diagnosis. Furthermore, IPS did not influence complete remission rate, disease-free survival, or overall survival. By investigating NPM1 status on separated cell compartments, we established a correlation between FC-assessed MLD and belonging to AML clone. This study shows that dysplasia evaluated by immunophenotype has no impact on clinical-biological characteristics or on outcome of NPM1⁺ AML. Dysplasia is part of the spectrum of NPM1⁺ AML, and the prognostic stratification of this category of patients should not be based upon it.
authors.affiliation: Unità Funzionale di Ematologia, Università degli Studi, AOU Careggi, Florence, Italy; Istituto Toscano Tumori, Florence, Italy. Electronic address: francesco.mannelli@unifi.it.
authors.forename: Francesco
authors.initials: F
authors.lastname: Mannelli
authors.affiliation: Unità Funzionale di Ematologia, Università degli Studi, AOU Careggi, Florence, Italy; Istituto Toscano Tumori, Florence, Italy.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Ponziani
authors.affiliation: Unità Funzionale di Ematologia, Università degli Studi, AOU Careggi, Florence, Italy; Istituto Toscano Tumori, Florence, Italy.
authors.forename: Maria Ida
authors.initials: MI
authors.lastname: Bonetti
authors.affiliation: Unità Funzionale di Ematologia, Università degli Studi, AOU Careggi, Florence, Italy; Istituto Toscano Tumori, Florence, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Bencini
authors.affiliation: Unità Funzionale di Ematologia, Università degli Studi, AOU Careggi, Florence, Italy; Istituto Toscano Tumori, Florence, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Cutini
authors.affiliation: Unità Funzionale di Ematologia, Università degli Studi, AOU Careggi, Florence, Italy; Istituto Toscano Tumori, Florence, Italy.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Gianfaldoni
authors.affiliation: Unità Funzionale di Ematologia, Università degli Studi, AOU Careggi, Florence, Italy; Istituto Toscano Tumori, Florence, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Scappini
authors.affiliation: Unità Funzionale di Ematologia, Università degli Studi, AOU Careggi, Florence, Italy; Istituto Toscano Tumori, Florence, Italy.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Pancani
authors.affiliation: SOD Laboratorio Centrale, Settore Citometria Clinica, AOU Careggi, Florence, Italy.
authors.forename: Tommaso
authors.initials: T
authors.lastname: Rondelli
authors.affiliation: SOD Diagnostica Genetica, AOU Careggi, Florence, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Benelli
authors.affiliation: SOD Laboratorio Centrale, Settore Citometria Clinica, AOU Careggi, Florence, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Caporale
authors.affiliation: SOD Laboratorio Centrale, Settore Citometria Clinica, AOU Careggi, Florence, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Grazia Gelli
authors.affiliation: SOD Laboratorio Centrale, Settore Citometria Clinica, AOU Careggi, Florence, Italy.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Peruzzi
authors.affiliation: Unità Funzionale di Ematologia, Università degli Studi, AOU Careggi, Florence, Italy; Istituto Toscano Tumori, Florence, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Longo
authors.affiliation: Unità Funzionale di Ematologia, Università degli Studi, AOU Careggi, Florence, Italy; Istituto Toscano Tumori, Florence, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Bosi
mesh_terms: D000328:Adult; D000368:Aged; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000235:genetics / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D000090243:Nucleophosmin; D015996:Survival Rate
chemical_list: C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin