Children's Blood and Cancer Centre, KK Women's and Children's Hospital, Singapore 229899, Singapore.
Duke-NUS Medical School, Singapore 169857, Singapore.
Int J Mol Sci. 2024 Sep 7;25(17):9704. doi: 10.3390/ijms25179704.
Acute leukemia is a group of aggressive hematological malignancies, with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) being the most common types. The biology of acute leukemia involves complex genetic and epigenetic alterations that lead to uncontrolled cell proliferation and resistance to apoptosis. Mitochondrial dysfunction is a feature of acute leukemia that results in altered energy production, unregulated cell death pathways, and increased cancer cell survival. Apoptosis, particularly via the mitochondrial pathway, is crucial for cellular homeostasis and cancer prevention. In acute leukemia, disruption of apoptosis is pivotal in disease development and progression, with elevated levels of anti-apoptotic proteins conferring a survival advantage to leukemia cells and promoting resistance to conventional therapies. Targeting mitochondrial apoptosis using BH3 mimetics and anti-apoptotic protein inhibitors is a viable therapeutic strategy. Alterations in the mitochondrial membrane potential, metabolism, and dynamics also contribute to the pathogenesis of acute leukemia. Continued research is vital for developing novel therapies and enhancing survival outcomes in patients with acute leukemia while minimizing the long-term adverse effects of treatment. In this narrative review, we provide a birds-eye view of the available scientific literature on the importance of mitochondria in acute leukemia, and discuss the role of BH3 mimetics in targeting the mitochondrial internal apoptotic machinery.
急性白血病是一组侵袭性血液系统恶性肿瘤,其中急性淋巴细胞白血病(ALL)和急性髓系白血病(AML)最为常见。急性白血病的生物学涉及复杂的遗传和表观遗传改变,导致不受控制的细胞增殖和对细胞凋亡的抵抗。线粒体功能障碍是急性白血病的一个特征,导致能量产生改变、不受调节的细胞死亡途径和增加的癌细胞存活。细胞凋亡,特别是通过线粒体途径,对于细胞稳态和癌症预防至关重要。在急性白血病中,细胞凋亡的破坏在疾病的发展和进展中起着关键作用,抗细胞凋亡蛋白水平升高赋予白血病细胞生存优势,并促进对常规治疗的抵抗。使用 BH3 模拟物和抗凋亡蛋白抑制剂靶向线粒体凋亡是一种可行的治疗策略。线粒体膜电位、代谢和动力学的改变也导致急性白血病的发病机制。继续研究对于开发新的治疗方法和提高急性白血病患者的生存结果至关重要,同时最大限度地减少治疗的长期不良反应。在这篇叙述性综述中,我们提供了有关线粒体在急性白血病中的重要性的现有科学文献的概述,并讨论了 BH3 模拟物在靶向线粒体内部凋亡机制中的作用。