Primary central nervous system lymphomas (PCNSLs) are angiocentric neoplasia which present dense monoclonal lymphocyte proliferation, and occur in brain parenchyma in 90% of the cases. Activated B-cell like Diffuse Large B-cell Lymphoma (ABC-DLBCL) subtype represents more than 90% of PCNSLs and is the most aggressive subtype with a cure rate of only 40%. One of the characteristics of ABC-DLBCL subtype is neuroinflammation through the activation of NF-kappaB pathway. c-Myc alterations and protein expression have been shown in aggressive DLBCL. c-Myc is considered as a key prognostic and predictive biomarker for survival in DLBCL, its expression is associated with worst survival rates. Although mRNA of c-Myc is increased by low levels gains of c-Myc, several studies have shown that c-Myc protein expression is overexpressed without c-Myc abnormalities. These high levels of c-Myc protein in DLBCL without genetic abnormalities suggest that c-Myc protein expression may be also increased by other mechanisms or signaling pathways which regulate its expression. In PCNSLs, the canonical WNT/beta- catenin pathway is upregulated while PPAR gamma is downregulated. The opposite interplay between WNT/beta-catenin pathway and PPAR gamma is reviewed here. Activation of WNT/beta-catenin pathway leads to the transcription of genes involved in cell proliferation, mitochondrial metabolism, protein synthesis, and tumor growth, such as c-Myc. PPAR gamma agonists induce the inhibition of several signaling pathways such as NF-kappaB, STAT, PI3K/Akt and WNT/beta-catenin pathway. Activation of PPAR gamma agonists may have a major negative key role in the regulation of PCNSLs progression.

中文翻译：

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原发性中枢神经系统淋巴瘤中典型 WNT/β-连环蛋白通路与 PPAR γ 之间相反相互作用的假设。

原发性中枢神经系统淋巴瘤（PCNSLs）是血管中心性肿瘤，表现为密集的单克隆淋巴细胞增殖，90% 的病例发生在脑实质。活化的 B 细胞样弥漫性大 B 细胞淋巴瘤 (ABC-DLBCL) 亚型占 PCNSL 的 90% 以上，是最具侵袭性的亚型，治愈率仅为 40%。ABC-DLBCL 亚型的特征之一是通过激活 NF-kappaB 通路的神经炎症。c-Myc 改变和蛋白质表达已在侵袭性 DLBCL 中显示。c-Myc 被认为是 DLBCL 存活的关键预后和预测生物标志物，其表达与最差的存活率相关。虽然 c-Myc 的 mRNA 会因 c-Myc 的低水平增益而增加，几项研究表明，c-Myc 蛋白表达过度表达而没有 c-Myc 异常。没有遗传异常的DLBCL中这些高水平的c-Myc蛋白表明c-Myc蛋白的表达也可能通过调节其表达的其他机制或信号通路增加。在 PCNSLs 中，经典的 WNT/β-连环蛋白途径被上调，而 PPAR γ 被下调。WNT/β-连环蛋白通路和 PPAR γ 之间相反的相互作用在这里进行了综述。WNT/β-连环蛋白通路的激活导致参与细胞增殖、线粒体代谢、蛋白质合成和肿瘤生长的基因转录，例如 c-Myc。PPAR γ 激动剂可诱导多种信号通路的抑制，例如 NF-kappaB、STAT、PI3K/Akt 和 WNT/β-连环蛋白通路。