Читать книгу The Peripheral T-Cell Lymphomas - Группа авторов - Страница 54

Methylation pathway genes (TET2, DNMT3, and IDH2) are altered in ATLL, albeit to a far less extent than in AITL. Polycomb‐dependent repression is enhanced in ATLL by trimethylation of histone lysine 27 and affects half the genes in ATLL. EZH2 and other components of the PRC2 complex are upregulated in ATLL. This biology suggests that EZH2 inhibitors may have a potential role in this particular subtype. While to date this experience is limited, pharmacologic inhibition of EZH2 results in apoptosis of ATLL cells. The genes that are commonly affected include several tumor‐suppressor genes like BCL2L11 (BIM), and CDKN1A and CD7. KDM6B, a gene that encodes a lysine‐specific demethylase that specifically demethylates di‐ or tri‐methylated lysine 27 of histone H3 is considered a repressive histone mark controlling chromatin condensation. The gene is downregulated in ATLL, thus locking in the effects initiated by Tax even when Tax expression is lost during disease progression [75].