Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and Fas apoptosis in Burkitt's lymphomas with loss of multiple pro-apoptotic proteins.
OBJECTIVE
Normal B-cells in the germinal center (GC) may be exposed to both tumor necrosis factor-related apoptosis inducing ligand (TRAIL) and Fas-L. Whether abrogation of TRAIL apoptosis is a feature in the genesis of B cell lymphomas of GC-phenotype is not known. We assessed the integrity of the TRAIL pathway in Fas-resistant and Fas-sensitive Burkitt s lymphomas (BLs).


METHODS
Expression of TRAIL receptors was determined by flow cytometry and Western blots. The extent of apoptosis following exposure to TRAIL was measured by annexin-V/propidium iodide dual staining. The integrity of the Fas and TRAIL apoptotic pathways was determined by Western blotting to assess cleavage of downstream caspases. Western blot analyses were used to determine the expression of pro- and anti-apoptotic proteins and the profile of expression was correlated with response to TRAIL and CH11.


RESULTS
Our results demonstrate that BL expresses both functional and decoy TRAIL receptors. BLs with a functional Fas pathway retained sensitivity to TRAIL: Frequent and compound loss of expression of pro-apoptotic proteins can be identified in BLs resistant to Fas. However, loss of Bax, Bak and Bcl-Xs did not compromise sensitivity to TRAIL:


CONCLUSIONS
Our results indicate that BLs frequently retain sensitivity to the TRAIL pathway. These results underscore the utility of TRAIL-based therapeutic strategies in the treatment of those B-cell lymphomas that may have compromised expression of several pro-apoptotic proteins.
Hussain
Azhar
A
KFNCCCR, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
Doucet
Jean-Pierre
JP
Gutiérrez
Marina
M
Ahmad
Manzoor
M
Al-Hussein
Khaled
K
Capello
Daniela
D
Gaidano
Gianluca
G
Bhatia
Kishor
K
D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D002051:Burkitt Lymphoma / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D020169:Caspases / Q000378:metabolism; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism* / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis; D053221:TNF-Related Apoptosis-Inducing Ligand; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism* / Q000502:physiology; D019014:fas Receptor / Q000378:metabolism* / Q000502:physiology
D051017:Apoptosis Regulatory Proteins; D008562:Membrane Glycoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; D018124:Receptors, Tumor Necrosis Factor; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D020169:Caspases