Expression and pro-survival function of phospholipase Cγ2 in diffuse large B-cell lymphoma

• Published in: Leukemia & lymphoma 2015-04, Vol.56 (4), p.1088-1095
• Main Authors: Huynh, Minh Q., Goßmann, Jennifer, Gattenlöehner, Stefan, Klapper, Wolfram, Wacker, Hans-Heinrich, Ramaswamy, Annette, Bittner, Alwina, Kaiser, Ulrich, Neubauer, Andreas
• Format: Article
• Language: English
• Subjects: Apoptosis - drug effects; Apoptosis - genetics; B cell receptor; Blotting, Western; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Proliferation - genetics; Cell Survival - drug effects; Cell Survival - genetics; DLBCL; Estrenes - pharmacology; Flow Cytometry; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Lymphoma, Large B-Cell, Diffuse - enzymology; Lymphoma, Large B-Cell, Diffuse - genetics; Lymphoma, Large B-Cell, Diffuse - pathology; overall survival; Phosphodiesterase Inhibitors - pharmacology; Phospholipase C gamma - antagonists & inhibitors; Phospholipase C gamma - genetics; Phospholipase C gamma - metabolism; PKCβ; PLCγ2; Pyrrolidinones - pharmacology; Reverse Transcriptase Polymerase Chain Reaction; RNA Interference; signaling pathway; Survival Analysis; Time Factors
• ISSN: 1042-8194; 1029-2403
• DOI: 10.3109/10428194.2014.941832

Abstract Diffuse large B-cell lymphoma (DLBCL) can be cured in about 60% of cases with immuno-chemotherapy. However, a large subset of patients with DLBCL do not go into remission, or relapse after first-line therapy. Further therapy options are therefore needed. Phospholipase Cγ2 (PLCγ2) is one of the key regulators of the B cell receptor signaling pathway, which targets several pro-proliferative factors, such as nuclear factor κB (NFκB), Ras and Akt. Using immunohistochemistry, we found that PLCγ2 was strongly expressed in 63% of cases of DLBCL. The PLC inhibitor U73122 had an inhibitory effect on cell proliferation and induced apoptosis and G0/G1 cell cycle arrest. Co-treatment with enzastaurin or the Src inhibitor pp2 together with U73122 had an additive effect on cell proliferation compared to U73122 alone. Unexpectedly, strong PLCγ2 expression was associated with better overall survival. In conclusion, PLCγ2 is strongly expressed in a significant number of DLBCLs and has prognostic implications. Inhibition of PLCγ2 could be a new target for lymphoma treatment.