Читать книгу The Peripheral T-Cell Lymphomas - Группа авторов - Страница 64

Protein arginine methyltransferases inhibitors (PRMTs) catalyze the monomethylation or dimethylation of arginine residues on histone and non‐histone proteins. A total of nine human PRMTs are known to exist, although PRMT5 seems to be the most relevant to oncogenesis. PRMT5 is a type II PRMT that specifically catalyzes the symmetrical dimethylation of arginine residues located on the H3 or H4 proteins, resulting in gene silencing [118]. PRMT5 might also have a role in the development of TCLs. Similar to EBV‐transformed lymphoma, PRMT5 expression is upregulated in human T‐cell lymphotropic virus type 1 (HTLV)‐transformed ATLL, and PRMT5 inhibition was shown to have selective cytotoxic effects on HTLV+ lymphoma cells [130]. Overexpression of PRMT5 in ATLL seems to interact with oncogenic CCND1, MYC, and NOTCH1 in driving lymphomagenesis and might also directly silence p53 [131]. No PRMT inhibitors have thus far received FDA approval, and the first clinical trial designed to investigate a PRMT5 inhibitor (GSK3326595) commenced in 2016 for patients with solid tumors or non‐Hodgkin lymphoma (NCT02783300). Despite this lack of clinical evidence, a growing body of data from preclinical studies has demonstrated a potentially important role of this class of drug, specifically for the treatment of lymphoid malignancies. Activating mutations in PRMT5 have not been reported in patients with lymphoma, although PRMT5 is overexpressed in different subtypes and might potentially serve as a biomarker.