Mitosis is the process whereby an eukaryotic cell divides into two identical copies. Different multiprotein complexes are involved in the fine regulation of cell division, including the mitotic promoting factor and the anaphase promoting complex. Prolonged mitosis can result in cellular division, cell death, or mitotic slippage, the latter leading to a new interphase without cellular division. Mitotic slippage is one of the causes of genomic instability and has an important therapeutic and clinical impact. It has been widely studied in solid tumors but not in hematological malignancies, in particular, in acute leukemia. We review the literature data available on mitotic regulation, alterations in mitotic proteins occurring in acute leukemia, induction of prolonged mitosis and its consequences, focusing in particular on the balance between cell death and mitotic slippage and on its therapeutic potentials. We also present the most recent preclinical and clinical data on the efficacy of second-generation mitotic drugs (CDK1-Cyclin B1, APC/CCDC20, PLK, Aurora kinase inhibitors). Despite the poor clinical activity showed by these drugs as single agents, they offer a potential therapeutic window for synthetic lethal combinations aimed to selectively target leukemic cells at the right time, thus decreasing the risk of mitotic slippage events.

中文翻译：

---

急性白血病中有丝分裂死亡与有丝分裂滑移之间的平衡：新的治疗窗口？

有丝分裂是真核细胞分裂成两个相同拷贝的过程。不同的多蛋白复合物参与细胞分裂的精细调节，包括有丝分裂促进因子和后期促进复合物。长时间的有丝分裂会导致细胞分裂，细胞死亡或有丝分裂滑移，后者导致新的无细胞分裂的间期。有丝分裂滑移是基因组不稳定的原因之一，并具有重要的治疗和临床影响。它已在实体瘤中进行了广泛研究，但在血液系统恶性肿瘤中却没有进行过研究，特别是在急性白血病中。我们回顾了有关有丝分裂调节，急性白血病中发生的有丝分裂蛋白变化，诱导有丝分裂时间延长及其后果的文献资料，特别着重于细胞死亡与有丝分裂滑移之间的平衡及其治疗潜力。我们还提供了有关第二代有丝分裂药物（CDK1-Cyclin B1，APC / CCDC20，PLK，Aurora激酶抑制剂）功效的最新临床前和临床数据。尽管这些药物作为单一药物显示出不良的临床活性，但它们为合成致死性组合提供了潜在的治疗窗口，旨在在适当的时间选择性靶向白血病细胞，从而降低了有丝分裂滑脱事件的风险。