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Doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) has been regarded as the standard treatment regimen for classical Hodgkin lymphoma. In recent years, ABVD-like regimens, which emerged due to shortages and the lung toxicity of bleomycin or the emergence of immune checkpoint inhibitors and antibody-drug conjugates, may be favorable, but have not yet been tested.We compared the outcomes of ABVD with ABVD-like regimens, which include bleomycin was completely or partially omitted; meanwhile, etoposide or PD-1 inhibitors were added.5-Year progression-free survival (PFS) was higher for ABVD than ABVD-like regimens in young patients (82.1% vs. 67.0%, p = 0.029), patients with serum beta-2 microglobulin (β2-MG) ≥ 1.85 mg/L (75.8% vs. 57.6%, p = 0.046), and advanced-stage patients with IPS score 4-7(63.1%, 18.3%, p = 0.038). For elderly (60.5% vs.76.1%, p = 0.089), patients with β2-MG 1.85 mg/L (83.1% vs 76.1%, p = 0.282), and advanced-stage patients with IPS score 0-3(84.6% vs. 81.3%, p = 0.476), 5-year PFS for ABVD did not differ from ABVD-like regimens. Elderly patients treated with bleomycin-free regimens showed a better survival trend compared with ABVD (99.3% vs. 61.3%, p = 0.270).ABVD is superior to ABVD-like regimens in achieving PFS in young patients or patients with poor prognosis including high IPS score and β2-MG level. ABVD-like regimens are as effective as ABVD in elderly or low-risk patients including low IPS score and β2-MG level; elderly patients treated with bleomycin-free regimens exhibit a better survival trend compared with ABVD.

Background Natural killer/T cell lymphoma (NKTCL) is a distinct subtype of Non-Hodgkin's lymphoma with highly aggressive clinical behavior. We aim to investigate the function of Latent transforming growth factor β binding protein 1 (LTBP1) and transforming growth factor beta1 (TGF-β1) and complex molecular pathogenesis of this disease. Methods NKTCL patients and reactive lymph nodes patients were recruited in this study. The expression of LTBP1 and TGF-β1 was examined using qRT-PCR, Western blot, IHC and ELISA analyses in biopsied tissues and serum from participants and NKTCL cell lines. Cell proliferation was determined using CFSE. Cell cycle and apoptosis were evaluated using flow cytometric analyses. The expression of Ki-67, CDK4 and cyclinD1 proteins was measured using Western blot analyses. The roles of LTBP-1/TGF-β1 in EMT program were determined by measuring E-cadherin, N-cadherin and Vimentin using Western blot analyses. The effects of LTBP-1 and TGF-β1 on tumor progression in vivo were determined by animal experiments. Results LTBP-1 and TGF-β1 levels were elevated in NKTCL tissues and serum. The expression of LTBP-1 was positively correlated with the expression of TGF-β1 in NKTCL tissues. LTBP-1 was overexpressed in NKTCL cells. Knockdown of LTBP-1 suppressed cell proliferation and cell cycle progression, induced cell apoptosis, and suppressed EMT program in NKTCL cells. These effects of LTBP-1 knockdown were attenuated after TGF-β1 stimulation. Knockdown of LTBP-1 inhibited NKTCL tumor weight and volume in vivo. Also, stimulation of TGF-β1 attenuated the suppressive effects on tumor growth from sh-LTBP-1. Silencing of LTBP-1 lowered cellular TGF-β1, phosphorylated-Smad2, phosphorlyatd-Smad3, and phosphorylated-p38 and the suppressive effects were reversed after stimulation of TGF-β1. Conclusion Our findings suggested that inhibition of LTBP-1/TGF-β1 suppressed the malignant phenotypes of NKTCL cells and tumor growth via inactivating the canonical TGF-β/Smad signaling and p38MAPK signaling.

Background: Epigenetic regulation plays vital roles in the oncogenesis and treatment of diffuse large B-cell lymphoma (DLBCL). The H3K9me3-specific histone methyltransferase SUV39H1 is an epigenetic gene that promotes the progression of a variety of malignancies. However, the roles of SUV39H1 in DLBCL remain unclear.Methods: Initially, the Oncomine, Cancer Cell Line Encyclopedia (CCLE), UALCAN and Gene Expression Profiling Interactive Analysis (GEPIA) databases were searched to explore the expression of SUV39H1 in DLBCL. The clinical parameters and pathological sections of 61 successive patients, including 47 cases of DLBCL and 14 cases of reactive lymphoid hyperplasia, were collected from January 2019 to November 2020. Immunohistochemistry was conducted to verify the results of the database search. Finally, relevant parameters and pathological results were combined to analyze the expression of SUV39H1.Results: We found that the expression of SUV39H1 in DLBCL tissues was higher than that in normal and other cancer tissues (PP=0.037), suggesting that patients with high SUV39H1 expression are less likely to develop tumors over 7.5 cm in size. Regarding survival, the group with high SUV39H1 expression had a lower survival rate than the group with low SUV39H1 expression in terms of 10-year disease-free survival (DFS) according to the database analyses (P=0.035). However, SUV39H1 was revealed as an independent predictor of overall survival (OS) and progression-free survival (PFS) in patients from both databases and our hospital (P>0.05).Conclusion: SUV39H1 expression is higher in DLBCL tissues than in normal and other cancer tissues, indicating that DLBCL patients may not develop bulky tumors over follow-up and suggesting that SUV39H1 might serve not only as a predictive factor in the clinic but also as a target for the epigenetic therapy of DLBCL.

Glycoprotein non-metastatic melanoma protein B (GPNMB) has been confirmed to be related to the pathogenesis of tumors. However, the potential impact of GPNMB on the progression of diffuse large B-cell lymphoma (DLBCL) is unclear. In this study, the expression levels of GPNMB and Yes-associated protein (YAP) were analyzed using qRT-PCT and Western blot assay. Cell counting kit-8, EdU, and flow cytometry assays were used to detect the proliferation and apoptosis of DLBCL cells. A nude mice xenograft model was established for in vivo research. Results showed that GPNMB and YAP1 were upregulated in DLBCL cell lines. Knockdown of GPNMB inhibited cell proliferation and promoted apoptosis in DLBCL cells. Additionally, the expression levels of YAP1 and the downstream effector of Hippo pathway (c-myc) were markedly decreased when GPNMB was knocked down. Moreover, knockdown of GPNMB inhibited the nuclear translocation of β-catenin protein, which could be abolished by YAP1 overexpression. Simultaneously, the anti-proliferative and pro-apoptotic effects of GPNMB knockdown could be reversed by YAP1 overexpression or LiCl (the activator of Wnt/β-catenin pathway). Furthermore, the mice xenograft model confirmed that inhibition of GPNMB restrained the tumorigenesis of DLBCL in vivo. In conclusion, GPNMB could partly activate the Wnt/β-catenin signaling pathway by targeting YAP1, so as to participate in tumorigenesis of DLBCL.