TY - JOUR AU - Daisuke Sasaki, AU - Yoshitaka Imaizumi, AU - Hiroo Hasegawa, AU - Akemi Osaka, AU - Kunihiro Tsukasaki, AU - Young Lim Choi, AU - Hiroyuki Mano, AU - Victor E. Marquez, AU - Tomayoshi Hayashi, AU - Katsunori Yanagihara, AU - Yuji Moriwaki, AU - Yasushi Miyazaki, AU - Shimeru Kamihira, AU - Yasuaki Yamada, PY - 2011/04/29 Y2 - 2024/03/29 TI - Overexpression of enhancer of zeste homolog 2 with trimethylation of lysine 27 on histone H3 in adult T-cell leukemia/lymphoma as a target for epigenetic therapy JF - Haematologica JA - haematol VL - 96 IS - 5 SE - Articles DO - 10.3324/haematol.2010.028605 UR - https://haematologica.org/article/view/5967 SP - 712-719 AB - Background Enhancer of zeste homolog 2 is a component of the Polycomb repressive complex 2 that mediates chromatin-based gene silencing through trimethylation of lysine 27 on histone H3. This complex plays vital roles in the regulation of development-specific gene expression.Design and Methods In this study, a comparative microarray analysis of gene expression in primary adult T-cell leukemia/lymphoma samples was performed, and the results were evaluated for their oncogenic and clinical significance.Results Significantly higher levels of Enhancr of zeste homolog 2 and RING1 and YY1 binding protein transcripts with enhanced levels of trimethylation of lysine 27 on histone H3 were found in adult T-cell leukemia/lymphoma cells compared with those in normal CD4+ T cells. Furthermore, there was an inverse correlation between the expression level of Enhancer of zeste homolog 2 and that of miR-101 or miR-128a, suggesting that the altered expression of the latter miRNAs accounts for the overexpression of the former. Patients with high Enhancer of zeste homolog 2 or RING1 and YY1 binding protein transcripts had a significantly worse prognosis than those without it, indicating a possible role of these genes in the oncogenesis and progression of this disease. Indeed, adult T-cell leukemia/lymphoma cells were sensitive to a histone methylation inhibitor, 3-deazaneplanocin A. Furthermore, 3-deazaneplanocin A and histone deacetylase inhibitor panobinostat showed a synergistic effect in killing the cellsConclusions These findings reveal that adult T-cell leukemia/lymphoma cells have deregulated Polycomb repressive complex 2 with over-expressed Enhancer of zeste homolog 2, and that there is the possibility of a new therapeutic strategy targeting histone methylation in this disease. ER -