Nucleophosmin in Acute Myelogenous Leukemia

Abstract

Falini et al. (Jan. 20 issue)¹ report an abnormal cytoplasmic localization of nucleophosmin (NPM) in 35 percent of specimens from patients with acute myelogenous leukemia. In these patients the NPM gene was mutated, which resulted in a frame shift. The authors state that tryptophan residues at positions 288 and 290 of NPM played a role in the cytoplasmic translocation of NPM. However, these residues are responsible only for nucleolar localization of NPM, not for cytoplasmic localization.² We found a motif containing leucine-valine residues, known as the nuclear-export-signal (NES) motif, in the C-terminal of mutated NPMs A to F in Figure 4B of the article ( Figure 1 ). The typical nuclear-export signal consists of a short stretch of hydrophobic amino acids (predominantly leucines) and fits the consensus sequence Lx(1-3)Lx(2-3)LxL (with x indicating any residues).³ NES-containing molecules are recognized by nuclear export receptor CRM1 and are then exported to cytoplasm.⁴ We believe that the NES generated by the mutation of the NPM gene is important for cytoplasmic localization of NPM and tumorigenesis in acute myelogenous leukemia.