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

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 C gamma 2 (PLC gamma 2) is one of the key regulators of the B cell receptor signaling pathway, which targets several proproliferative factors, such as nuclear factor kappa B (NF kappa B), Ras and Akt. Using immunohistochemistry, we found that PLC gamma 2 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 PLC gamma 2 expression was associated with better overall survival. In conclusion, PLC gamma 2 is strongly expressed in a significant number of DLBCLs and has prognostic implications. Inhibition of PLC gamma 2 could be a new target for lymphoma treatment.