{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T14:24:24Z","timestamp":1766067864827,"version":"build-2065373602"},"reference-count":119,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,11,10]],"date-time":"2023-11-10T00:00:00Z","timestamp":1699574400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Romanian Academy of Scientists (Academia Oamenilor de Stiinta din Romania) 2023\u20132024","award":["15\/11 April 2023","PN-III-P4-ID-PCE-1957 PCE185\/2021","771\/3\/11 January 2023"],"award-info":[{"award-number":["15\/11 April 2023","PN-III-P4-ID-PCE-1957 PCE185\/2021","771\/3\/11 January 2023"]}]},{"name":"European Economic Space between Romania and Iceland 2021\u20132023","award":["15\/11 April 2023","PN-III-P4-ID-PCE-1957 PCE185\/2021","771\/3\/11 January 2023"],"award-info":[{"award-number":["15\/11 April 2023","PN-III-P4-ID-PCE-1957 PCE185\/2021","771\/3\/11 January 2023"]}]},{"name":"Romanian National Ministry of Research, Innovation, and Digitalization","award":["15\/11 April 2023","PN-III-P4-ID-PCE-1957 PCE185\/2021","771\/3\/11 January 2023"],"award-info":[{"award-number":["15\/11 April 2023","PN-III-P4-ID-PCE-1957 PCE185\/2021","771\/3\/11 January 2023"]}]},{"name":"PCD","award":["15\/11 April 2023","PN-III-P4-ID-PCE-1957 PCE185\/2021","771\/3\/11 January 2023"],"award-info":[{"award-number":["15\/11 April 2023","PN-III-P4-ID-PCE-1957 PCE185\/2021","771\/3\/11 January 2023"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/cimb45110563","type":"journal-article","created":{"date-parts":[[2023,11,13]],"date-time":"2023-11-13T08:44:27Z","timestamp":1699865067000},"page":"8974-8988","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The Role of Epigenetic Modifier Mutations in Peripheral T-Cell Lymphomas"],"prefix":"10.3390","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9397-0791","authenticated-orcid":false,"given":"Adrian-Bogdan","family":"Tigu","sequence":"first","affiliation":[{"name":"Medfuture Research Center for Advanced Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania"},{"name":"Academy of Romanian Scientists, Ilfov 3, 050044 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6475-9866","authenticated-orcid":false,"given":"Anamaria","family":"Bancos","sequence":"additional","affiliation":[{"name":"Medfuture Research Center for Advanced Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania"},{"name":"Department of Hematology, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"47","DOI":"10.3322\/caac.21589","article-title":"The rapidly changing landscape in mature T-cell lymphoma (MTCL) biology and management","volume":"70","author":"Marchi","year":"2020","journal-title":"CA Cancer J. 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