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Aberrant cytoplasmic expression of C-terminal-truncated NPM leukaemic mutant is dictated by tryptophans loss and a new NES motif

Leukemia volume 21, pages 2052–2054 (2007)Cite this article

In acute myeloid leukaemia (AML), NPM1 gene mutations occur almost exclusively at exon 12.1 Therefore, we read with great interest the recent letter by Pitiot et al.2 on a novel type of mutation occurring at exon 11 of the NPM1 gene, which generates a 274-amino-acid NPM leukaemic mutant truncated at its C-terminal end. This mutation is very similar to the one we previously described.3 Specifically, we first identified a truncated form of NPM protein generated by a mutation at NPM1 exon 11, which localizes aberrantly in the cytoplasm of leukaemic cells due to the concerted action of two abnormalities: loss of tryptophan residues 288 and 290 (which impairs the mutated NPM protein capability to bind nucleoli) and the new Rev-type NES motif (VFLI) at the mutant C terminus.3 We concluded that a common molecular theme4 underlies the exaggerated nuclear export and cytoplasmic accumulation of NPM mutants in NPMc+ AML carrying mutations either at exon 12 or 11.

In their paper, Pitiot et al.2 claim that, despite the bulk of the mutated NPM protein is aberrantly localized in the cytoplasm, some of it is localized in the nucleoli. On the basis of this finding, they speculated that ‘in this case the wild-type protein would not be sequestered in the cytoplasm when forming heterodimers with the mutant protein, as has been suggested to occur with the described exon 12-NPM1 mutants’.2

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References

  1. Falini B, Mecucci C, Tiacci E, Alcalay M, Rosati R, Pasqualucci L et al. Cytoplasmic nucleophosmin in acute myelogenous leukemia with a normal karyotype. N Engl J Med 2005; 352: 254–266.

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Authors and Affiliations

  1. Institute of Haematology, University of Perugia, Perugia, Italy

    B Falini, N Bolli, M F De Marco & M Martelli

  2. Department of Cell Therapy and Haematology, San Bortolo Hospital, Vicenza, Italy

    E Albiero, D Madeo & F Rodeghiero

  3. Institute of Internal Medicine, University of Perugia, Perugia, Italy

    I Nicoletti

Authors
  1. B Falini
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  2. E Albiero
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  3. N Bolli
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  4. M F De Marco
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  5. D Madeo
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  6. M Martelli
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  7. I Nicoletti
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  8. F Rodeghiero
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Correspondence to B Falini.

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Falini, B., Albiero, E., Bolli, N. et al. Aberrant cytoplasmic expression of C-terminal-truncated NPM leukaemic mutant is dictated by tryptophans loss and a new NES motif. Leukemia 21, 2052–2054 (2007). https://doi.org/10.1038/sj.leu.2404839

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