Imatinib Sensitizes T-cell Lymphocytes From Chronic Myeloid Leukemia Patients to FasL-induced Cell Death: A Brief Communication

被引:6
作者
Legros, Laurence [1 ,2 ]
Ebran, Nathalie [2 ]
Stebe, Emmanuelle [2 ]
Rousselot, Philippe [3 ]
Rea, Delphine [4 ,5 ]
Cassuto, Jill Patrice
Mahon, Francois-Xavier [6 ]
Hueber, Anne-Odile [2 ]
机构
[1] Archet 1 Hosp, Dept Hematol, Serv Hematol Clin, F-06202 Nice 3, France
[2] Univ Nice, CNRS, Inst Dev Biol & Canc Res, F-06034 Nice, France
[3] Ctr Hosp Versailles, Versailles, France
[4] Hop St Louis, AP HP, Serv Malad Sang, Paris, France
[5] Hop St Louis, AP HP, Unite Therapie Cellulaire, Paris, France
[6] CHU Bordeaux, Hematol Lab, Bordeaux, France
关键词
chronic myeloid leukemia; imatinib; Fas/CD95; cell death; lymphocyte; RECEPTOR; ACTIVATION; KIT; PROLIFERATION; MICE;
D O I
10.1097/CJI.0b013e318243f238
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
There is now substantial evidence that imatinib may affect immune responses, especially those mediated by T lymphocytes. Fas (CD95/Apo-1), a cell death receptor, is a key regulator of the immune system. We have explored the consequences of treatment on the Fas system in chronic myeloid leukemia patients treated with imatinib. In comparison with healthy controls, we found not only a mild blood lymphopenia but also impairment of phytohemagglutinin activation in CD4(+)Fas(+) and CD8(+)Fas(+) lymphocytes of imatinib-treated patients. Moreover, these lymphocyte populations were more sensitive to FasL-induced cell death in relation to an increase in Fas expression at the cell surface. Taken together, these results reveal the role of Fas receptor in the lymphopenia observed in patients treated with imatinib, with potential deleterious consequences on antileukemic responses against this immunogenic hematological malignancy.
引用
收藏
页码:154 / 158
页数:5
相关论文
共 13 条
[1]   Critical role for Kit-mediated Src kinase but not PI 3-kinase signaling in pro T and pro B cell development [J].
Agosti, V ;
Corbacioglu, S ;
Ehlers, I ;
Waskow, C ;
Sommer, G ;
Berrozpe, G ;
Kissel, H ;
Tucker, CM ;
Manova, K ;
Moore, MAS ;
Rodewald, HR ;
Besmer, P .
JOURNAL OF EXPERIMENTAL MEDICINE, 2004, 199 (06) :867-878
[2]   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].
Boissel, Nicolas ;
Rousselot, Philippe ;
Raffoux, Emmanuel ;
Cayuela, Jean-Michel ;
Soulier, Jean ;
Mooney, Nuala ;
Charron, Dominique ;
Dombret, Herve ;
Toubert, Antoine ;
Rea, Delphine .
JOURNAL OF LEUKOCYTE BIOLOGY, 2006, 79 (04) :747-756
[3]   Imatinib inhibits the activation and proliferation of normal T lymphocytes in vitro [J].
Cwynarski, K ;
Laylor, R ;
Macchiarulo, E ;
Goldman, J ;
Lombardi, G ;
Melo, JV ;
Dazzi, F .
LEUKEMIA, 2004, 18 (08) :1332-1339
[4]   Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia [J].
Druker, Brian J. ;
Guilhot, Francois ;
O'Brien, Stephen G. ;
Gathmann, Insa ;
Kantarjian, Hagop ;
Gattermann, Norbert ;
Deininger, Michael W. N. ;
Silver, Richard T. ;
Goldman, John M. ;
Stone, Richard M. ;
Cervantes, Francisco ;
Hochhaus, Andreas ;
Powell, Bayard L. ;
Gabrilove, Janice L. ;
Rousselot, Philippe ;
Reiffers, Josy ;
Cornelissen, Jan J. ;
Hughes, Timothy ;
Agis, Hermine ;
Fischer, Thomas ;
Verhoef, Gregor ;
Shepherd, John ;
Saglio, Giuseppe ;
Gratwohl, Alois ;
Nielsen, Johan L. ;
Radich, Jerald P. ;
Simonsson, Bengt ;
Taylor, Kerry ;
Baccarani, Michele ;
So, Charlene ;
Letvak, Laurie ;
Larson, Richard A. .
NEW ENGLAND JOURNAL OF MEDICINE, 2006, 355 (23) :2408-2417
[5]   Imatinib mesylate suppresses cytokine synthesis by activated CD4 T cells of patients with chronic myelogenous leukemia [J].
Gao, H ;
Lee, BN ;
Talpaz, M ;
Donato, NJ ;
Cortes, JE ;
Kantarjian, HM ;
Reuben, JM .
LEUKEMIA, 2005, 19 (11) :1905-1911
[6]   Discontinuation of imatinib in patients with chronic myeloid leukaemia who have maintained complete molecular remission for at least 2 years: the prospective, multicentre Stop Imatinib (STIM) trial [J].
Mahon, Francois-Xavier ;
Rea, Delphine ;
Guilhot, Joelle ;
Guilhot, Francois ;
Huguet, Francoise ;
Nicolini, Franck ;
Legros, Laurence ;
Charbonnier, Aude ;
Guerci, Agnes ;
Varet, Bruno ;
Etienne, Gabriel ;
Reiffers, Josy ;
Rousselot, Philippe .
LANCET ONCOLOGY, 2010, 11 (11) :1029-1035
[7]   The CD95 receptor: Apoptosis revisited [J].
Peter, Marcus E. ;
Budd, Ralph C. ;
Desbarats, Julie ;
Hedrick, Stephen M. ;
Hueber, Anne-Odile ;
Newell, M. Karen ;
Owen, Laurie B. ;
Tschopp, Juerg ;
Wajant, Harald ;
Wallach, David ;
Wiltrout, Robert H. ;
Zornig, Martin ;
Lynch, David H. .
CELL, 2007, 129 (03) :447-450
[8]   Involvement of death receptor Fas in germ cell degeneration in gonads of Kit-deficient Wv/Wv mutant mice [J].
Sakata, S ;
Sakamaki, S ;
Watanabe, K ;
Nakamura, N ;
Toyokuni, S ;
Nishimune, Y ;
Mori, C ;
Yonehara, S .
CELL DEATH AND DIFFERENTIATION, 2003, 10 (06) :676-686
[9]   Imatinib inhibits T-cell receptor-mediated T-cell proliferation and activation in a dose-dependent manner [J].
Seggewiss, R ;
Loré, K ;
Greiner, E ;
Magnusson, MK ;
Price, DA ;
Douek, DC ;
Dunbar, CE ;
Wiestner, A .
BLOOD, 2005, 105 (06) :2473-2479
[10]  
Steegmann JL, 2003, HAEMATOLOGICA, V88, P762