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- Title
Human soluble TRAIL/Apo2L induces apoptosis in a subpopulation of chemotherapy refractory nodal diffuse large B-cell lymphomas, determined by a highly sensitive in vitro apoptosis assay.
- Authors
Cillessen, Saskia A. G. M.; Meijer, Chris J. L. M.; Ossenkoppele, Gert J.; Castricum, Kitty C. M.; Westra, August H.; Niesten, Petra; Muris, Jettie J. F.; Nijdam, Hoite F.; van der Hem, Klaas G.; Flens, Marcel; Hooijberg, Erik; Oudejans, Joost J.
- Abstract
Resistance to chemotherapy in therapy-refractory diffuse large B-cell lymphomas (DLBCL) is related to inhibition of the intrinsic apoptosis pathway. Human soluble tumour necrosis factor (TNF)-related apoptosis-inducing ligand (hsTRAIL/Apo2L) induces apoptosis via the alternative, death-receptor mediated apoptosis pathway and might be an effective alternative form of therapy for these lymphomas. This study investigated whether hsTRAIL/Apo2L could actually induce apoptosis in isolated lymphoma cells of DLBCL biopsies of patients with chemotherapy-refractory DLBCL. Twelve out of a total of 22 DLBCL samples were sensitive to hsTRAIL/Apo2L. These sensitive lymphomas included seven clinically chemotherapy-refractory lymphomas. Furthermore, hsTRAIL/Apo2L induced apoptosis in DLBCL cells and in B-cell lines that showed high expression levels of inhibitors of the intrinsic apoptosis pathway: Bcl-2 and/or X-linked inhibitor of apoptosis (XIAP). hsTRAIL/Apo2L-sensitive lymphoma cells showed expression of the TRAIL receptors R1 and/or R2 and absence of R3 and R4. We conclude that hsTRAIL/Apo2L induced apoptosis in a subpopulation of chemotherapy-refractory nodal DLBCL and that disruption of the intrinsic apoptosis-mediated pathway and expression of Bcl-2 and XIAP did not confer resistance to hsTRAIL/Apo2L-induced apoptosis in DLBCL. Thus, based on our results, further exploration of hsTRAIL/Apo2L as an alternative treatment for patients with chemotherapy-refractory DLBCL should be considered.
- Subjects
DRUG therapy; B cells; LYMPHOMAS; APOPTOSIS; TUMOR necrosis factors; CLINICAL pathology; ALTERNATIVE medicine
- Publication
British Journal of Haematology, 2006, Vol 134, Issue 3, p283
- ISSN
0007-1048
- Publication type
Article
- DOI
10.1111/j.1365-2141.2006.06186.x