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Blood, 1 April 2005, Vol. 105, No. 7, pp. 2916-2923. Prepublished online as a Blood First Edition Paper on December 2, 2004; DOI 10.1182/blood-2004-07-2716. This Article Full Text (PDF) All Versions of this Article: 2004-07-2716v1 105/7/2916    most recent 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 Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Muris, J. J Articles by Oudejans, J. J Search for Related Content PubMed PubMed Citation Articles by Muris, J. J Articles by Oudejans, J. J Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 16, 2004 Accepted November 26, 2004 Immuno-histochemical profiling of caspase signaling pathways predicts clinical response to chemotherapy in primary nodal diffuse large B-cell lymphomas Jettie J Muris, Saskia A Cillessen, Wim Vos, Inge S van Houdt, J A Kummer, J van Krieken, N M Jiwa, Patty M Jansen, Hanneke C Kluin-Nelemans, Gert J Ossenkoppele, Chad Gundy, Chris J Meijer, and Joost J Oudejans* Department of Pathology, VU Medical Center, Amsterdam, The Netherlands Department of Clinical Pathology, Utrecht Medical Center, Utrecht, The Netherlands Department of Clinical Pathology, Radboud University Medical Center, Nijmegen, The Netherlands Department of Clinical Pathology, Medical Center Alkmaar, Alkmaar, The Netherlands Department of Clinical Pathology, LUMC, Amsterdam, The Netherlands Department of Hematology, University Hospital Groningen, Groningen, The Netherlands Department of Haematology, VU Medical Center, Amsterdam, The Netherlands Department of Clinical Epidemiology and Biostatistics, VU Medical Center, Amsterdam, The Netherlands * Corresponding author; email: jj.oudejans{at}vumc.nl. We investigated whether inhibition of caspase 8 and/or 9 apoptosis signaling pathways predicts clinical outcome in biopsy specimens of primary nodal diffuse large B-cell lymphomas (DLBCL). Expression levels of c-Flip and numbers of active caspase 3 positive lymphoma cells were used to determine the status of the caspase 8 mediated pathway. Expression levels of Bcl-2 and XIAP were used to determine the status of the caspase 9 mediated pathway. Expression of c-FLIP, XIAP and Bcl-2 and caspase 3 activity all provided prognostic information. According to these immuno-histochemical parameters, inhibition of either or both caspase signaling pathways was detected in all cases. Three groups were identified: one with a caspase 8 inhibition profile, one with a caspase 8 and 9 inhibition profile and one with a caspase 9 inhibition profile. A caspase 9 inhibition profile was strongly associated with poor response to chemotherapy and a usually fatal outcome, whereas a caspase 8 inhibition profile was associated with excellent clinical outcome. Thus, our data strongly suggest that inhibition of the caspase 9 and not the caspase 8 mediated pathway is a major cause for therapy resistance in patients with nodal DLBCL. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. A. G. M. Cillessen, J. C. Reed, K. Welsh, C. Pinilla, R. Houghten, E. Hooijberg, J. Deurhof, K. C. M. Castricum, P. Kortman, C. J. Hess, et al. Small-molecule XIAP antagonist restores caspase-9 mediated apoptosis in XIAP-positive diffuse large B-cell lymphoma cells Blood, January 1, 2008; 111(1): 369 - 375. [Abstract] [Full Text] [PDF] S. A.G.M. Cillessen, C. J. Hess, E. Hooijberg, K. C.M. Castricum, P. Kortman, F. Denkers, W. Vos, M. A. van de Wiel, G. J. Schuurhuis, G. J. Ossenkoppele, et al. Inhibition of the Intrinsic Apoptosis Pathway Downstream of Caspase-9 Activation Causes Chemotherapy Resistance in Diffuse Large B-Cell Lymphoma Clin. Cancer Res., December 1, 2007; 13(23): 7012 - 7021. [Abstract] [Full Text] [PDF] J. C van Galen, J. J F Muris, J. J Oudejans, W. Vos, C. P E Giroth, G. J Ossenkoppele, A. P Otte, F. M Raaphorst, and C. J L M Meijer Expression of the polycomb-group gene BMI1 is related to an unfavourable prognosis in primary nodal DLBCL J. Clin. Pathol., February 1, 2007; 60(2): 167 - 172. [Abstract] [Full Text] [PDF] A. S.K. de Hooge, D. Berghuis, S. J. Santos, E. Mooiman, S. Romeo, J. A. Kummer, R. M. Egeler, M. J.D. van Tol, C. J.M. Melief, P. C.W. Hogendoorn, et al. Expression of Cellular FLICE Inhibitory Protein, Caspase-8, and Protease Inhibitor-9 in Ewing Sarcoma and Implications for Susceptibility to Cytotoxic Pathways Clin. Cancer Res., January 1, 2007; 13(1): 206 - 214. [Abstract] [Full Text] [PDF] S. Uddin, A. R. Hussain, A. K. Siraj, P. S. Manogaran, N. A. Al-Jomah, A. Moorji, V. Atizado, F. Al-Dayel, A. Belgaumi, H. El-Solh, et al. Role of phosphatidylinositol 3'-kinase/AKT pathway in diffuse large B-cell lymphoma survival Blood, December 15, 2006; 108(13): 4178 - 4186. [Abstract] [Full Text] [PDF] I. S. Lossos and D. Morgensztern Prognostic Biomarkers in Diffuse Large B-Cell Lymphoma J. Clin. Oncol., February 20, 2006; 24(6): 995 - 1007. [Abstract] [Full Text] [PDF] N. Casares, M. O. Pequignot, A. Tesniere, F. Ghiringhelli, S. Roux, N. Chaput, E. Schmitt, A. Hamai, S. Hervas-Stubbs, M. Obeid, et al. Caspase-dependent immunogenicity of doxorubicin-induced tumor cell death J. Exp. Med., December 19, 2005; 202(12): 1691 - 1701. [Abstract] [Full Text] [PDF]

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