Inhibition of caspase 9 and not caspase 8 mediated apoptosis may determine clinical response to chemotherapy in primary nodal diffuse large B-cell lymphomas.
Clinical response to chemotherapy in patients with diffuse large B-cell lymphomas is poorly predictable. We demonstrated that an expression profile consistent with inhibition of the stress-induced, caspase 9 mediated apoptosis pathway predicts poor clinical response to chemotherapy, whereas an expression profile consistent with inhibition of only the death-receptor induced, caspase 8 mediated pathway was associated with an excellent response to chemotherapy and favorable outcome. Furthermore, functional analysis of apoptosis sensitivity showed that lymphomas with a caspase 9 inhibition profile were indeed relatively resistant to Etoposide induced apoptosis. Determining the functional status of both apoptosis signaling pathways may accurately identify patients at high risk for fatal outcome and may have implications for alternative therapies triggering the death receptor mediated apoptosis pathway.
Oudejans
Joost J
JJ
Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands. jj.Oudejans@vumc.nl
Muris
Jettie J F
JJ
Meijer
Chris J L M
CJ
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D053181:Caspase 8; D053453:Caspase 9; D061945:Caspase Inhibitors; D019008:Drug Resistance, Neoplasm; D004791:Enzyme Inhibitors; D005047:Etoposide / Q000494:pharmacology; D006801:Humans; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000473:pathology; D008954:Models, Biological; D012306:Risk; D015398:Signal Transduction; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D005047:Etoposide; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053181:Caspase 8; D053453:Caspase 9