CD30 protects EBV‐positive diffuse large B‐cell lymphoma cells against mitochondrial dysfunction through increasing BNIP3 expression

Introduction: EBV-positive diffuse large B-cell lymphoma (EBV+DLBCL) predicts poor prognosis. Studies have found that CD30 expression was more frequent in EBV+DLBCL patients compared to EBV-negative (EBV-) DLBCL and high associated with survivals EBV+DLBCL. All these facts suggested a synergistic effect between EBV infection. Methods: FARAGE GM12878 are type II III latency EBV-infected B cell lines while RAJI DAUDI I. SUDHL-2, U2932 RIVA lines. CRISPR/Cas9 editing employed engineer the loss-of-function models of genes involved this study. Results: A total 451 were included results showed had worse PFS (P = 0.007) OS when co-expressed EBER (Figure 1A). Immunoblot analysis higher than I 1B). Relevant experiments indicated tumor cells demonstrated rapid proliferation less susceptible apoptosis 1C 1D) CD30-KO mice significantly smaller size wild (WT) 1E). LMP1 overexpression resulted 1F). To elucidate how regulated CD30, we increased p-Btk p-p65 1G). detected decrease treated ibrutinib (a BTK inhibitor) also abolished LMP1-induced p-IκBα 1H). We performed gene following KO depression inhibited BNIP3 1I). group lower those control 1J). IHC staining revealed significant 1K). by system led fall MMP 1L). Moreover, accumulation damaged mitochondria observed CD30-deficient TEM 1M). Above silencing mitochondrial damage inhibition activity. As identified as target for investigated Collectively, our validated an important role promoting 1N 1O). Keywords: Aggressive non-Hodgkin lymphoma, Molecular Targeted Therapies, Tumor Biology Heterogeneity No conflicts interests pertinent abstract.