Multilineage dysplasia has no impact on biologic, clinicopathologic, and prognostic features of AML with mutated nucleophosmin (NPM1).

TY - JOUR

T1 - Multilineage dysplasia has no impact on biologic, clinicopathologic, and prognostic features of AML with mutated nucleophosmin (NPM1).

AU - Falini, Brunangelo

AU - Macijewski, Katja

AU - Weiss, Tamara

AU - Bacher, Ulrike

AU - Schnittger, Susanne

AU - Kern, Wolfgang

AU - Kohlmann, Alexander

AU - Klein, Hans-Ulrich

AU - Vignetti, Marco

AU - Piciocchi, Alfonso

AU - Fazi, Paola

AU - Martelli, Maria Paola

AU - Vitale, Antonella

AU - Pileri, Stefano

AU - Miesner, Miriam

AU - Santucci, Antonella

AU - Haferlach, Claudia

AU - Mandelli, Franco

AU - Haferlach, Torsten

PY - 2010

Y1 - 2010

N2 - 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.

AB - 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.

M3 - SCORING: Zeitschriftenaufsatz

VL - 115

SP - 3776

EP - 3786

JO - BLOOD

JF - BLOOD

SN - 0006-4971

IS - 18

M1 - 18

ER -