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Altered natural killer cell differentiation in CD34+ progenitors from Chronic Myeloid Leukemia patients

Oncogene volume 19, pages 2758–2766 (2000)Cite this article

Abstract

IL-15 and SCF fail to induce NK differentiation and proliferation of CD34+ hematopoietic progenitors from chronic myeloid leukemia patients in contrast to normal stem cells although, both normal and leukemic CD34+ cells display comparable expression of c-kit or IL-15 receptor subunits. Interestingly, confocal microscopy analysis revealed that leukemic and most normal CD34+ cells produce and secrete IL-15, as shown by its trafficking through the Golgi apparatus and early endosomes. However, only leukemic progenitors express the membrane bound IL-15. Colocalization and internalization of IL-15Rβ/γc and IL-15Rα/γc complexes indicated that IL-15 was specifically uptaken by leukemic progenitors. We also demonstrated that in both normal and leukemic progenitors, the signaling kinase Jak3 is constitutively pre-associated with the γc chain. Anti-IL-15 neutralizing mAb treatment resulted in down-regulation of γc chain and disruption of γc/Jak3 interaction in normal but had no effect in leukemic progenitors. Our results suggest the existence in both normal and leukemic CD34+ cells of a constitutive production of a bioactive IL-15 that does not lead to NK differentiation and further indicate that membrane bound IL-15 and constitutive activation of γc are hallmarks of leukemic progenitors.

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Acknowledgements

We would like to thank Yann Lécluse for immunofluorescence analyses and Maryvonne Guillard for excellent technical assistance. This work was supported by INSERM, IFR 54 Institute Gustave Roussy, ARC 3055 (Villejuif, France) and LNCC (comité Val de Marne, France).

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Author notes

  1. Géraldine Carayol and Julien Giron-Michel: These authors contributed equally to this work

Authors and Affiliations

  1. INSERM U487, Institut Gustave Roussy, 39, rue Camille Desmoulins, Villejuif, 94805, France

    Géraldine Carayol, Luca Castagna, Jean-Henri Bourhis, Salem Chouaib & Anne Caignard

  2. Service d'Hématologie, Institut Gustave Roussy, 39, rue Camille Desmoulins, Villejuif, 94805, France

    Jean-Henri Bourhis

  3. INSERM 506, Hôpital Paul Brousse, Villejuif, 94807, France

    Julien Giron-Michel & Bruno Azzarone

  4. Service d'Hématologie, CHU de Lille, France

    Nathalie Cambier

  5. CNRS UPS 47 laboratoire de cytomètrie, Villejuif, 94807, France

    Zohar Mishal

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  1. Géraldine Carayol
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Carayol, G., Giron-Michel, J., Azzarone, B. et al. Altered natural killer cell differentiation in CD34+ progenitors from Chronic Myeloid Leukemia patients. Oncogene 19, 2758–2766 (2000). https://doi.org/10.1038/sj.onc.1203584

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