Tigu Adrian-Bogdan, Bancos Anamaria
Medfuture Research Center for Advanced Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania.
Academy of Romanian Scientists, Ilfov 3, 050044 Bucharest, Romania.
Curr Issues Mol Biol. 2023 Nov 10;45(11):8974-8988. doi: 10.3390/cimb45110563.
Peripheral T-cell lymphomas (PTCLs) are a group of diseases with a low incidence, high degree of heterogeneity, and a dismal prognosis in most cases. Because of the low incidence of these diseases, there have been few therapeutic novelties developed over time. Nevertheless, this fact is changing presently as epigenetic modifiers have been shown to be recurrently mutated in some types of PTCLs, especially in the cases of PTCLs not otherwise specified (PTCL-NOS), T follicular helper (TFH), and angioimmunoblastic T-cell lymphoma (AITL). These have brought about more insight into PTCL biology, especially in the case of PTCLs arising from TFH lymphocytes. From a biological perspective, it has been observed that ten-eleven translocators (TET2) mutated T lymphocytes tend to polarize to TFH, while Tregs lose their inhibitory properties. IDH2 R172 was shown to have inhibitory effects on TET2, mimicking the effects of TET2 mutations, as well as having effects on histone methylation. DNA methyltransferase 3A (DNMT3A) loss-of-function, although it was shown to have opposite effects to TET2 from an inflammatory perspective, was also shown to increase the number of T lymphocyte progenitors. Aside from bringing about more knowledge of PTCL biology, these mutations were shown to increase the sensitivity of PTCLs to certain epigenetic therapies, like hypomethylating agents (HMAs) and histone deacetylase inhibitors (HDACis). Thus, to answer the question from the title of this review: We found the Achilles heel, but only for one of the Achilles.
外周T细胞淋巴瘤（PTCLs）是一组发病率低、异质性高且多数病例预后不佳的疾病。由于这些疾病发病率低，长期以来开发的治疗新方法很少。然而，目前这一情况正在改变，因为表观遗传修饰因子已被证明在某些类型的PTCLs中经常发生突变，特别是在未另行指定的PTCLs（PTCL-NOS）、T滤泡辅助细胞（TFH）和血管免疫母细胞性T细胞淋巴瘤（AITL）病例中。这些发现为PTCL生物学带来了更多见解，尤其是在源自TFH淋巴细胞的PTCLs方面。从生物学角度来看，已经观察到十 - 十一易位酶（TET2）突变的T淋巴细胞倾向于向TFH极化，而调节性T细胞（Tregs）则失去其抑制特性。IDH2 R172被证明对TET2有抑制作用，模拟TET2突变的效果，同时对组蛋白甲基化也有影响。DNA甲基转移酶3A（DNMT3A）功能丧失，尽管从炎症角度来看其作用与TET2相反，但也被证明会增加T淋巴细胞祖细胞的数量。除了带来更多关于PTCL生物学的知识外，这些突变还被证明会增加PTCLs对某些表观遗传疗法的敏感性，如低甲基化剂（HMAs）和组蛋白去乙酰化酶抑制剂（HDACis）。因此，为了回答本综述标题中的问题：我们找到了阿喀琉斯之踵，但只是其中一只的。
