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

Géraldine Carayol, Julien Giron-Michel, Bruno Azzarone, Luca Castagna, Nathalie Cambier, Zohar Mishal, Jean Henri Bourhis, Salem Chouaib, Anne Caignard

Research output: Contribution to journalArticle

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 downregulation 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.

Original languageEnglish
Pages (from-to)2758-2766
Number of pages9
JournalOncogene
Volume19
Issue number23
Publication statusPublished - May 25 2000

Keywords

  • Chronic myeloid leukemia
  • IL-15
  • IL-15R
  • NK cell differentiation

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

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    Carayol, G., Giron-Michel, J., Azzarone, B., Castagna, L., Cambier, N., Mishal, Z., Bourhis, J. H., Chouaib, S., & Caignard, A. (2000). Altered natural killer cell differentiation in CD34+ progenitors from Chronic Myeloid Leukemia patients. Oncogene, 19(23), 2758-2766.