title: Expression and pro-survival function of phospholipase Cγ2 in diffuse large B-cell lymphoma.
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.
authors.affiliation: Department of Hematology, Oncology and Immunology, University Hospital , Marburg , Germany.
authors.forename: Minh Q
authors.initials: MQ
authors.lastname: Huynh
authors.forename: Jennifer
authors.initials: J
authors.lastname: Goßmann
authors.forename: Stefan
authors.initials: S
authors.lastname: Gattenlöehner
authors.forename: Wolfram
authors.initials: W
authors.lastname: Klapper
authors.forename: Hans-Heinrich
authors.initials: HH
authors.lastname: Wacker
authors.forename: Annette
authors.initials: A
authors.lastname: Ramaswamy
authors.forename: Alwina
authors.initials: A
authors.lastname: Bittner
authors.forename: Ulrich
authors.initials: U
authors.lastname: Kaiser
authors.forename: Andreas
authors.initials: A
authors.lastname: Neubauer
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D004963:Estrenes / Q000494:pharmacology; D005434:Flow Cytometry; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D016403:Lymphoma, Large B-Cell, Diffuse / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D051966:Phospholipase C gamma / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D011760:Pyrrolidinones / Q000494:pharmacology; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D013997:Time Factors
chemical_list: D004963:Estrenes; D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D051966:Phospholipase C gamma
keywords: B cell receptor; DLBCL; PKCβ; PLCγ2; overall survival; signaling pathway