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

Autor: Kitty C. M. Castricum, Joost J. Oudejans, Gert J. Ossenkoppele, Hoite F. Nijdam, Klaas G. Van Der Hem, Petra Niesten, Chris J.L.M. Meijer, Erik Hooijberg, A.H. Westra, Jettie J.F. Muris, Saskia A. G. M. Cillessen, Marcel J. Flens
Rok vydání: 2006
Předmět:
medicine.medical_treatment
Blotting
Western
CASP8 and FADD-Like Apoptosis Regulating Protein
Apoptosis
X-Linked Inhibitor of Apoptosis Protein
Inhibitor of apoptosis
Receptors
Tumor Necrosis Factor
TNF-Related Apoptosis-Inducing Ligand
immune system diseases
hemic and lymphatic diseases
Cell Line
Tumor
medicine
Humans
Fluorometry
B cell
Chemotherapy
Membrane Glycoproteins
Chemistry
Caspase 3
Tumor Necrosis Factor-alpha
Intrinsic apoptosis
Intracellular Signaling Peptides and Proteins
Hematology
medicine.disease
Immunohistochemistry
XIAP
Lymphoma
Receptors
TNF-Related Apoptosis-Inducing Ligand
medicine.anatomical_structure
Proto-Oncogene Proteins c-bcl-2
Drug Resistance
Neoplasm
Caspases
Lymphatic Metastasis
Cancer research
Tumor necrosis factor alpha
Lymphoma
Large B-Cell
Diffuse
Apoptosis Regulatory Proteins
Zdroj: British journal of haematology. 134(3)
ISSN: 0007-1048
Popis: Summary 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.
Databáze: OpenAIRE
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