A novel MEF2C mutation in lymphoid neoplasm diffuse large B-cell lymphoma promotes tumorigenesis by increasing c-JUN expression.

Diffuse large B-cell lymphoma (DLBCL) is the most aggressive non-Hodgkin lymphoma (NHL), accounting for about 31% of the newly diagnosed NHL worldwide. Although approximately 60% of patients who initially received a standard R-CHOP treatment likely have a 3-year event-free survival, many patients become refractory or relapsed due to the genetic heterogeneity of this malignancy. Hence, new treatment strategies are urgently needed. MEF2C, a member of the MEF2 transcription factor family gene, plays great important roles involved in the development of various tissues and the pathogenesis of lymphoma. However, the exact functions and molecular mechanisms of MEF2C in DLBCL are not fully investigated. By Sanger sequencing, we identified a novel point mutation of MEF2C at the p.N389 site in DLBCL patient, which was further validated by several DLBCL cell lines. Intriguingly, we found that the p.N389S mutation did not influence MEF2C expression, protein stability, and subcellular distribution, but enhanced its transcriptional activity. Furthermore, we demonstrated that MEF2C p.N389S mutation promotes DLBCL cell proliferation, cellular adhesion, and tumor formation in nude mice. On mechanism, our data revealed that MEF2C p.N389S mutation increases c-JUN expression, and c-JUN regulation mediated the oncogenic function of MEF2C p.N389S mutation on DLBCL cells. Our finding may provide a significant insight into the DLBCL and a compelling therapy target for this disease treatment.

Clinical research on expression levels of T lymphocytes and NK cells in patients with esophageal cancer treated with radiotherapy / 肿瘤研究与临床

Objective To study the relationship between the change of T lymphocyte subsets and NK cells in esophageal cancer patients and radiotherapy effect.Methods The levels of T lymphocyte subsets and NK cells were detected by flow cytometry in 56 cases with histologically confirmed esophageal cancer treated with radiotherapy and contrasted to the healthy people.Results In patients with esophageal cancer,peripheral blood T cells,Th cells,Th / Ts were decreased significantly compared with the control group [(58.3±5.2) ％ vs (65.8±7.2) ％,(28.7±5.0) ％ vs (38.1±7.7) ％,(1.0±0.3) vs (1.6+2.7),all P ＜ 0.05],while the Ts cells were significantly increased [(28.8±5.3) ％ vs (25.4±5.7) ％,P ＜ 0.05].There was no significant difference between peripheral blood T lymphocyte subsets,Th/Ts ratio change and patient age,sex,tumor staging,histological differentiation and pathological lesions.After radiotherapy,the levels of peripheral blood T cells,Th cells,Th/Ts cell ratio and NK cells in esophageal cancer patients were increased [(66.9±4.5) ％ vs (59.4±4.9) ％,(40.6±5.6) ％ vs (29.1±4.2) ％,(1.6+0.5) ％ vs (1.0±0.4) ％,(16.2±3.9) ％ vs (14.6±3.2) ％,all P ＜ 0.05],while the Ts cells decreased [ (25.4±3.6) ％ vs (28.4±5.7) ％,P ＜ 0.05].The increasing degree of peripheral blood T cells,Th cells were closely related to the lesion progress,the difference was significant (both P ＜ 0.05).Conclusion Cellular immune function in patients with esophageal cancer is low.Detection of T lymphocyte subsets,NK cells can be used for immune monitoring of patients with esophageal cancer.