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  • Letter to the Editor
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Reply to ‘Aberrant cytoplasmic expression of C-terminal truncated NPM leukaemic mutant is dictated by tryptophans loss and a new NES motif’ by Falini et al.

Leukemia volume 21, page 2054 (2007)Cite this article

We were surprised to see some of Falini's comments and disagreements on our letter,1 as we actually think that our results and interpretations are quite in accordance with their proposed hypothesis. As it is clearly stated in our report,2 we have never claimed that ‘despite of the bulk mutated NPM1 protein is aberrantly localized in the cytoplasm, some of it is localized in the nucleoli’; as we have analysed a sample from a heterozygous patient for the NPM1 mutation, we interpreted that the observed nucleolar staining pattern in the sample could be owing to the presence of the wild-type protein. If the wild-type protein can be sequestered or not in the cytoplasm by the newly described mutant is something that needs further investigation.

Regarding our immunofluorescence results with a commercially available antibody against NPM1 with samples heterozygous for the already described type-A mutation, we agree that some differences may exist with other studies. We have re-assayed additional samples containing type-A mutations in heterozygosis, and found nucleolar and cytoplasmic reactivity (Supplementary Figure 1). Again, when compared with the new insertional mutation described in our letter, cytoplasmic reactivity is clearly stronger in type-A mutants than in the C-terminal truncated NPM1 mutation. These results reinforce our idea that in some cases, depending on the type of antibody used, and even depending on the processing of samples, this truncating mutation might not be properly detected. Thus we would recommend, for clinical routine analysis, searching for NPM1 mutations by molecular biology methods from DNA/RNA obtained from patient samples.

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References

  1. Falini B, Albiero E, Bolli N, Madeo D, Martelli M, Nicoletti I et al. Aberrant cytoplasmic expression of C-terminal truncated NPM leukaemic mutant is dictated by tryptophan loss and a new NES motif. Leukemia 2007.

  2. Pitiot AS, Santamaria I, Garcia-Suarez O, Centeno I, Astudillo A, Rayón C et al. A new type of NPM1 gene mutation in AML leading to a C-terminal truncated protein. Leukemia 2007; e-pub ahead of print; 5 April.

  3. Albiero E, Madeo D, Bolli N, Giaretta I, Bona ED, Martelli MF et al. Identification and functional characterization of a cytoplasmic nucleophosmin leukaemic mutant generated by a novel exon-11 NPM1 mutation. Leukemia 2007; 21: 1099–1103.

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Authors and Affiliations

  1. Laboratorio de Oncología Molecular, Hospital Universitario Central de Asturias & Instituto Universitario de Oncología del Principado de Asturias, Oviedo, Spain

    A S Pitiot, I Santamaría, I Centeno & M Balbín

  2. Laboratorio de Apoyo a la Investigación del Banco de Tumores, Instituto Universitario de Oncología del Principado de Asturias, Oviedo, Spain

    O García-Suárez & A Astudillo

  3. Servicio de Anatomía Patológica, Hospital Universitario Central de Asturias, Oviedo, Spain

    A Astudillo

  4. Servicio de Hematología, Hospital Universitario Central de Asturias, Oviedo, Spain

    C Rayón

Authors
  1. A S Pitiot
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  2. I Santamaría
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  3. O García-Suárez
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  4. I Centeno
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  5. A Astudillo
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  6. C Rayón
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  7. M Balbín
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Corresponding author

Correspondence to M Balbín.

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Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu)

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Pitiot, A., Santamaría, I., García-Suárez, O. et al. Reply to ‘Aberrant cytoplasmic expression of C-terminal truncated NPM leukaemic mutant is dictated by tryptophans loss and a new NES motif’ by Falini et al.. Leukemia 21, 2054 (2007). https://doi.org/10.1038/sj.leu.2404840

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