Chai Jiani, Choudhuri Jui, Gong Jerald Z, Wang Yanhua, Tian Xuejun
Montefiore Medical Center, Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10467, USA.
Department of Pathology and Genomic Medicine, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA.
Cancers (Basel). 2024 Feb 2;16(3):646. doi: 10.3390/cancers16030646.
EZH2, a subunit of the polycomb repressive complex 2 (PRC2), is an important methyltransferase that catalyzes the trimethylation of histone H3 at lysine 27 (H3K27me3). EZH2 is overexpressed in various malignancies. Here, we investigated EZH2 expression and potential signaling molecules that correlate with EZH2 expression in ATLL and other T-cell neoplasms. Immunohistochemical staining (IHC) was performed for EZH2, pERK, MYC, and pSTAT3 on 43 ATLL cases and 104 cases of other T-cell neoplasms. Further IHC studies were conducted for Ki-67, SUZ12, and H3K27me3 on ATLL cases. All ATLL cases showed EZH2 overexpression. In other T-cell neoplasms, a high prevalence of EZH2 overexpression was identified (86%), except for T-PLL (33%). In ATLL, EZH2 overexpression correlated with pERK co-expression (86%), while only a small subset of cases showed MYC (7%) or pSTAT3 (14%) co-expression. In the other T-cell neoplasms, there was a variable, but higher, co-expression of EZH2 with pERK, MYC, and pSTAT3. In ATLL, enhanced EZH2 expression correlated with higher Ki-67 staining, SUZ12 (another PRC2 subunit), and H3K27me3 co-expression. In conclusion, EZH2 is overexpressed in ATLL and is associated with pERK expression. It correlates with an increased proliferation index, indicating an aggressive clinical course. EZH2 also correlates with SUZ12 and H3K27me3 co-expression, suggesting its PRC2-dependent catalytic activity through trimethylation. Additionally, EZH2 is overexpressed in most T-cell neoplasms, suggesting that EZH2 could function as an oncogenic protein in T-cell tumorigenesis. EZH2 and pERK could serve as potential therapeutic targets for treating aggressive ATLL. EZH2 could also be targeted in other T-cell neoplasms.
EZH2是多梳抑制复合物2（PRC2）的一个亚基，是一种重要的甲基转移酶，可催化组蛋白H3赖氨酸27位点的三甲基化（H3K27me3）。EZH2在多种恶性肿瘤中过表达。在此，我们研究了EZH2在成人T细胞白血病淋巴瘤（ATLL）和其他T细胞肿瘤中的表达情况以及与EZH2表达相关的潜在信号分子。对43例ATLL病例和104例其他T细胞肿瘤病例进行了EZH2、磷酸化细胞外信号调节激酶（pERK）、MYC和磷酸化信号转导和转录激活因子3（pSTAT3）的免疫组织化学染色（IHC）。对ATLL病例进一步进行了Ki-67、SUZ12和H3K27me3的IHC研究。所有ATLL病例均显示EZH2过表达。在其他T细胞肿瘤中，除T细胞幼淋巴细胞白血病（T-PLL，33%）外，EZH2过表达的发生率较高（86%）。在ATLL中，EZH2过表达与pERK共表达相关（86%），而只有一小部分病例显示MYC（7%）或pSTAT3（14%）共表达。在其他T细胞肿瘤中，EZH2与pERK、MYC和pSTAT3存在不同但更高的共表达。在ATLL中，EZH2表达增强与更高的Ki-67染色、SUZ12（PRC2的另一个亚基）和H3K27me3共表达相关。总之，EZH2在ATLL中过表达并与pERK表达相关。它与增殖指数增加相关，表明临床病程侵袭性强。EZH2还与SUZ12和H3K27me3共表达相关，提示其通过三甲基化发挥PRC2依赖性催化活性。此外，EZH2在大多数T细胞肿瘤中过表达，表明EZH2可能在T细胞肿瘤发生中作为致癌蛋白发挥作用。EZH2和pERK可作为治疗侵袭性ATLL的潜在治疗靶点。EZH2也可在其他T细胞肿瘤中作为靶点。
