Abstract
Acute myeloid leukemia carrying cytoplasmic mutated nucleophosmin (NPMc(+) AML) and blastic plasmacytoid dendritic cell neoplasm have been included as new entities in the 4(th) edition (2008) WHO classification of myeloid neoplasms. These conditions may show clinical and pathological overlapping features (leukemic and skin involvement, and expression of macrophage markers). In this study, we provide evidence that aberrant cytoplasmic dislocation of nucleophosmin - the immunohistochemical surrogate for NPM1 mutations - allows the two entities to be genetically separated. In fact, nucleophosmin is consistently cytoplasmic in NPMc(+) AML (because of the presence of NPM1 mutations), whilst it is nucleus-restricted (predictive of a germline NPM1 gene) in blastic plasmacytoid dendritic cell neoplasm. Our results clearly point cytoplasmic nucleophosmin (a full predictor of NPM1 mutations) as a new marker for distinguishing NPMc(+) AML and blastic plasmacytoid dendritic cell neoplasm, further clarify the cell of origin of NPMc(+) AML, and justify the inclusion of these pathological conditions as separate entities in the new WHO classification.
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