This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Terme, M. Articles by Zitvogel, L. Search for Related Content PubMed PubMed Citation Articles by Terme, M. Articles by Zitvogel, L.

BCR/ABL Promotes Dendritic Cell–Mediated Natural Killer Cell Activation

¹ ERM0208 Institut National de la Sante et de la Recherche Medicale, Department of Clinical Biology, Institut Gustave Roussy; ² Cytogenetic and Oncologic Genetic Laboratory, Institut Gustave Roussy; ³ Translational Research-Cell Therapy Laboratory and Institut National de la Sante et de la Recherche Medicale U362, Institut Gustave Roussy; ⁴ U487 Institut National de la Sante et de la Recherche Medicale, Villejuif, France; ⁵ Oncology Hematology and Cell Therapy, CHU La Milétrie, Poitiers, France; ⁶ Immunology Laboratory, Centre National de la Recherche Scientifique UMR8115, Genethon, Evry, France; ⁷ Institute of Molecular Pathology, Vienna, Austria; and ⁸ Laboratoire d'Immunologie Clinique, Hôpital Necker-Enfants malades, Paris, France

Requests for reprints: Laurence Zitvogel, Immunology Unit, ERM0208 Institut National de la Sante et de la Recherche Medicale, Department of Clinical Biology, Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif Cedex, France. Phone: 33-1-42-11-50-41; Fax: 33-1-42-11-60-94; E-mail: zitvogel{at}igr.fr.

BCR/ABL fusion gene, encoding a paradigmatic tyrosine kinase involved in chronic myelogenous leukemia (CML), can modulate the expression of genes involved in natural killer (NK) cell target recognition. Recent reports outline the role of allogeneic antileukemic NK effectors in the graft-versus-leukemia effect but the regulation of NK cell activation in the setting of graft-versus-leukemia effect remains unknown. Here we show that dendritic cells derived from monocytes of CML patients are selectively endowed with NK cell stimulatory capacity in vitro. We further show, using a gene transfer approach in mouse bone marrow progenitors, that ABL/ABL is necessary to promote dendritic cell–mediated NK cell activation. The dendritic cell/NK cell cross-talk in ABL/ABL-induced CML seems unique because JunB or IFN consensus sequence binding protein loss of functions, associated with other myeloproliferative disorders, do not promote dendritic cell–mediated NK cell activation. NK cell activation by leukemic dendritic cells involves NKG2D activating receptors and is blocked by imatinib mesylate. Indeed, ABL/ABL translocation enhances the expression levels of the NKG2D ligands on dendritic cells, which is counteracted by imatinib mesylate. Altogether, the clonal ABL/ABL dendritic cells display the unique and selective ability to activate NK cells and may participate in the NK cell control of CML. This study also highlights the deleterious role of imatinib mesylate at the dendritic cell level for NK cell activation.

This article has been cited by other articles:

				R. W. McGilvray, R. A. Eagle, N. F.S. Watson, A. Al-Attar, G. Ball, I. Jafferji, J. Trowsdale, and L. G. Durrant NKG2D Ligand Expression in Human Colorectal Cancer Reveals Associations with Prognosis and Evidence for Immunoediting Clin. Cancer Res., November 15, 2009; 15(22): 6993 - 7002. [Abstract] [Full Text] [PDF]

				R. Chakraverty and M. Sykes The role of antigen-presenting cells in triggering graft-versus-host disease and graft-versus-leukemia Blood, July 1, 2007; 110(1): 9 - 17. [Abstract] [Full Text] [PDF]

				N. Boissel, D. Rea, V. Tieng, N. Dulphy, M. Brun, J.-M. Cayuela, P. Rousselot, R. Tamouza, P. Le Bouteiller, F.-X. Mahon, et al. BCR/ABL oncogene directly controls MHC class I chain-related molecule A expression in chronic myelogenous leukemia. J. Immunol., April 15, 2006; 176(8): 5108 - 5116. [Abstract] [Full Text] [PDF]

				N. Boissel, P. Rousselot, E. Raffoux, J.-M. Cayuela, J. Soulier, N. Mooney, D. Charron, H. Dombret, A. Toubert, and D. Rea Imatinib mesylate minimally affects bcr-abl+ and normal monocyte-derived dendritic cells but strongly inhibits T cell expansion despite reciprocal dendritic cell-T cell activation J. Leukoc. Biol., April 1, 2006; 79(4): 747 - 756. [Abstract] [Full Text] [PDF]

				C. Cebo, S. Da Rocha, S. Wittnebel, A. G. Turhan, J. Abdelali, S. Caillat-Zucman, J. H. Bourhis, S. Chouaib, and A. Caignard The Decreased Susceptibility of Bcr/Abl Targets to NK Cell-Mediated Lysis in Response to Imatinib Mesylate Involves Modulation of NKG2D Ligands, GM1 Expression, and Synapse Formation J. Immunol., January 15, 2006; 176(2): 864 - 872. [Abstract] [Full Text] [PDF]