Multilineage dysplasia has no impact on biologic, clinicopathologic, and prognostic features ofAMLwith mutated nucleophosmin (NPM1)

Brunangelo Falini, Katja Macijewski, Tamara Weiss, Ulrike Bacher, Susanne Schnittger, Wolfgang Kern, Alexander Kohlmann, Hans Ulrich Klein, Marco Vignetti, Alfonso Piciocchi, Paola Fazi, Maria Paola Martelli, Antonella Vitale, Stefano Pileri, Miriam Miesner, Antonella Santucci, Claudia Haferlach, Franco Mandelli, Torsten Haferlach

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)3776-3786
Number of pages11
Issue number18
Publication statusPublished - May 6 2010

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology


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