Huynh Minh Q, Goßmann Jennifer, Gattenlöehner Stefan, Klapper Wolfram, Wacker Hans-Heinrich, Ramaswamy Annette, Bittner Alwina, Kaiser Ulrich, Neubauer Andreas
Department of Hematology, Oncology and Immunology, University Hospital , Marburg , Germany.
Leuk Lymphoma. 2015 Apr;56(4):1088-95. doi: 10.3109/10428194.2014.941832. Epub 2014 Sep 8.
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.
弥漫性大B细胞淋巴瘤（DLBCL）采用免疫化疗大约可治愈60%的病例。然而，很大一部分DLBCL患者一线治疗后未缓解或复发。因此需要更多的治疗选择。磷脂酶Cγ2（PLCγ2）是B细胞受体信号通路的关键调节因子之一，该通路靶向多种促增殖因子，如核因子κB（NFκB）、Ras和Akt。通过免疫组化，我们发现63%的DLBCL病例中PLCγ2呈强表达。PLC抑制剂U73122对细胞增殖有抑制作用，并诱导细胞凋亡和G0/G1期细胞周期阻滞。与单独使用U73122相比，恩杂他滨或Src抑制剂pp2与U73122联合治疗对细胞增殖具有相加作用。出乎意料的是，PLCγ2强表达与更好的总生存期相关。总之，PLCγ2在大量DLBCL中呈强表达并具有预后意义。抑制PLCγ2可能成为淋巴瘤治疗的新靶点。
