Department of Cardiology, The First College of Clinical Medical Science, China Three Gorges University and Yichang Central People's Hospital, Yichang, PR China.
Institute of Cardiovascular Diseases, China Three Gorges University, Yichang, PR China.
Histol Histopathol. 2024 Apr;39(4):425-435. doi: 10.14670/HH-18-658. Epub 2023 Aug 16.
Cell proliferation and differentiation are the basic physiological activities of cells. Mistakes in these processes may affect cell survival, or cause cell cycle dysregulation, such as tumorigenesis, birth defects and degenerative diseases. In recent years, it has been found that histone methyltransferase DOT1L is the only H3 lysine 79 methyltransferase, which plays an important role in the process of cell fate determination through monomethylation, dimethylation and trimethylation of H3K79. DOT1L has a pro-proliferative effect in leukemia cells; however, loss of heart-specific DOT1L leads to increased proliferation of cardiac tissue. Additionally, DOT1L has carcinogenic or tumor suppressive effects in different neoplasms. At present, some DOT1L inhibitors for the treatment of MLL-driven leukemia have achieved promising results in clinical trials, but completely blocking DOT1L will also bring some side effects. Thus, this uncertainty suggests that DOT1L has a unique function in cell physiology. In this review, we summarize the primary findings of DOT1L in regulating cell proliferation and differentiation. Correlations between DOT1L and cell fate specification might suggest DOT1L as a therapeutic target for diseases.
细胞增殖和分化是细胞的基本生理活动。这些过程中的错误可能会影响细胞存活，或导致细胞周期失调，如肿瘤发生、出生缺陷和退行性疾病。近年来，人们发现组蛋白甲基转移酶 DOT1L 是唯一的 H3 赖氨酸 79 甲基转移酶，它通过 H3K79 的单甲基化、二甲基化和三甲基化在细胞命运决定过程中发挥重要作用。DOT1L 在白血病细胞中有促增殖作用；然而，心脏特异性 DOT1L 的缺失会导致心脏组织的过度增殖。此外，DOT1L 在不同的肿瘤中具有致癌或抑癌作用。目前，一些用于治疗 MLL 驱动的白血病的 DOT1L 抑制剂在临床试验中取得了有希望的结果，但完全阻断 DOT1L 也会带来一些副作用。因此，这种不确定性表明 DOT1L 在细胞生理学中具有独特的功能。在这篇综述中，我们总结了 DOT1L 在调节细胞增殖和分化方面的主要发现。DOT1L 与细胞命运特化之间的相关性可能表明 DOT1L 是治疗疾病的一个有希望的靶点。
