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

@article{citeulike:2781997, abstract = {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. 10.1158/0008-5472.CAN-04-2675}, author = {Terme, Magali and Borg, Christophe and Guilhot, Francois and Masurier, Carole and Flament, Caroline and Wagner, Erwin F. and Caillat-Zucman, Sophie and Bernheim, Alain and Turhan, Ali G. and Caignard, Anne and Zitvogel, Laurence }, citeulike-article-id = {2781997}, doi = {10.1158/0008-5472.CAN-04-2675}, journal = {Cancer Res}, keywords = {ra, rae-1}, month = {July}, number = {14}, pages = {6409--6417}, posted-at = {2008-05-10 00:33:49}, priority = {2}, title = {BCR/ABL Promotes Dendritic Cell-Mediated Natural Killer Cell Activation}, url = {http://dx.doi.org/10.1158/0008-5472.CAN-04-2675}, volume = {65}, year = {2005} }

TY - JOUR ID - citeulike:2781997 TI - BCR/ABL Promotes Dendritic Cell-Mediated Natural Killer Cell Activation JF - Cancer Res VL - 65 IS - 14 SP - 6409 EP - 6417 N2 - 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. 10.1158/0008-5472.CAN-04-2675 KW - ra KW - rae-1 AU - Terme, Magali AU - Borg, Christophe AU - Guilhot, Francois AU - Masurier, Carole AU - Flament, Caroline AU - Wagner, Erwin AU - Caillat-Zucman, Sophie AU - Bernheim, Alain AU - Turhan, Ali AU - Caignard, Anne AU - Zitvogel, Laurence PY - 2005/07/15/ UR - http://dx.doi.org/10.1158/0008-5472.CAN-04-2675 ER -