Euchromatic histone-lysine N-methyltransferase 1 (EHMT1) and EHMT2 are upregulated in various human cancers, and their deregulation is associated with tumor development and progression. In this paper, we investigated the expression level of EHMT1/EHMT2 in acute lymphoblastic leukemia (ALL) and whether the modulation of these enzymes could have any cellular or molecular impact on ALL cells. For this, we used UNC0646 as a priming strategy to target EHMT1/EHMT2 and investigated its effect on proliferation and cell viability of Jurkat cells by MTT assay. Then, considering the IC50 and IC75, cellular death was determined by Annexin V/PI staining using flow cytometry. Finally, we investigated by RT-PCR the molecular bases that could be involved in the observed effects. Interestingly, accessing the International Microarray Innovations in Leukemia (MILE) study group, we detected that both EHMT1 and EHMT2 are overexpressed in ALL. More important, we determined that inhibition of EHMT1/EHMT2 significantly decreased Jurkat cell viability in a dose-dependent manner. Accordingly, we observed that inhibition of EHMT1/EHMT2 promoted Jurkat cell death, which was accompanied by increased expression of P53, TP73, BAX, and MDM4. These results clearly indicate that inhibition of EHMT1/EHMT2 induces pro-apoptotic gene expression in ALL and promotes cell death. More importantly, the modulation of these histone methyltransferases may be a promising epigenetic target for ALL treatment.

常染色质组蛋白-赖氨酸N-甲基转移酶 1 (EHMT1) 和 EHMT2 在各种人类癌症中上调，它们的失调与肿瘤的发展和进展有关。在本文中，我们研究了EHMT1/EHMT2的表达水平在急性淋巴细胞白血病 (ALL) 中以及这些酶的调节是否会对 ALL 细胞产生任何细胞或分子影响。为此，我们使用 UNC0646 作为靶向 EHMT1/EHMT2 的启动策略，并通过 MTT 测定研究其对 Jurkat 细胞增殖和细胞活力的影响。然后，考虑 IC50 和 IC75，使用流式细胞术通过膜联蛋白 V/PI 染色确定细胞死亡。最后，我们通过 RT-PCR 研究了可能参与观察到的效果的分子基础。有趣的是，通过访问国际白血病微阵列创新 (MILE) 研究组，我们发现 EHMT1 和 EHMT2 在 ALL 中都过表达。更重要的是，我们确定抑制 EHMT1/EHMT2 以剂量依赖性方式显着降低 Jurkat 细胞活力。因此，我们观察到 EHMT1/EHMT2 的抑制促进了 Jurkat 细胞死亡，伴随着 P53、TP73、BAX 和 MDM4 的表达增加。这些结果清楚地表明，抑制 EHMT1/EHMT2 会诱导 ALL 中的促凋亡基因表达并促进细胞死亡。更重要的是，这些组蛋白甲基转移酶的调节可能是 ALL 治疗的一个有希望的表观遗传靶点。