TY - JOUR
T1 - Multilineage dysplasia has no impact on biologic, clinicopathologic, and prognostic features ofAMLwith 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 - 2010/5/6
Y1 - 2010/5/6
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.
UR - http://www.scopus.com/inward/record.url?scp=77952578145&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77952578145&partnerID=8YFLogxK
U2 - 10.1182/blood-2009-08-240457
DO - 10.1182/blood-2009-08-240457
M3 - Article
C2 - 20203266
AN - SCOPUS:77952578145
VL - 115
SP - 3776
EP - 3786
JO - Blood
JF - Blood
SN - 0006-4971
IS - 18
ER -