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Sensitivity and Resistance to Therapy

Increase sensitivity to chemotherapeutical agents and cytoplasmatic interaction between NPM leukemic mutant and NF-κB in AML carrying NPM1 mutations

Leukemia volume 22, pages 1234–1240 (2008)Cite this article

A Retraction to this article was published on 08 April 2010

Abstract

Mutations in nucleophosmin (NPM) exon 12 and the resulting delocalization of NPM into the cytoplasm are the most specific and frequent cellular events in acute myeloid leukemia patients (AML) with normal karyotype. Cytoplasmatic NPM (NPMc+) is associated with responsiveness to chemotherapy and better prognosis. The activation of nuclear factor-κB (NF-κB) has been demonstrated to occur in a subset of AML patients and is thought to induce resistance to many chemotherapeutical agents. In this study, we demonstrate the increased in vitro sensitivity of NPMc+ cells to chemotherapeutical agents and their reduced NF-κB activity. Furthermore, we provide evidence of the interaction between NPMc+ and NF-κB in the cytoplasm, resulting in the sequestration and inactivation of NF-κB. The cytosolic localization and consequent inactivation of NF-κB justifies the reduced NF-κB DNA-binding activity observed in NPMc+ patients. These data, taken together, may provide a possible explanation for the increased rate of chemosensitivity observed among the NPMc+ patients.

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Acknowledgements

This work has been supported by grants from AIRC (Associazione Italiana per la Ricerca sul Cancro), MURST-COFIN, AIL (Associazione Italiana contro le Leucemie) and Regione Piemonte.

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Author notes

  1. D Cilloni and F Messa: These authors contributed equally to this work.

  2. E Messa: EM is a fellow of Gigi Ghirotti Foundation.

Authors and Affiliations

  1. Division of Hematology and Internal Medicine, Department of Clinical and Biological Sciences of the University of Turin, Turin, Italy

    D Cilloni, F Messa, V Rosso, F Arruga, I Defilippi, S Carturan, R Catalano, M Pautasso, C Panuzzo, P Nicoli, E Messa, A Morotti, E Bracco & G Saglio

  2. Department of Hematology and Oncological Sciences, Division of Hematology, Seragnoli Institute, University of Bologna, Bologna, Italy

    I Iacobucci & G Martinelli

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Correspondence to D Cilloni.

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Cilloni, D., Messa, F., Rosso, V. et al. Increase sensitivity to chemotherapeutical agents and cytoplasmatic interaction between NPM leukemic mutant and NF-κB in AML carrying NPM1 mutations. Leukemia 22, 1234–1240 (2008). https://doi.org/10.1038/leu.2008.68

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