Department of Clinical Laboratory Medicine, Saga-Ken Medical Centre Koseikan, Saga 840-8571, Japan.
Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga 849-8501, Japan.
Int J Mol Sci. 2024 Nov 14;25(22):12219. doi: 10.3390/ijms252212219.
The most important issues in acute myeloid leukemia are preventing relapse and treating relapse. Although the remission rate has improved to approximately 80%, the 5-year survival rate is only around 30%. The main reasons for this are the high relapse rate and the limited treatment options. In chronic myeloid leukemia patients, when a deep molecular response is achieved for a certain period of time through tyrosine kinase inhibitor treatment, about half of them will reach treatment-free remission, but relapse is still a problem. Therefore, potential therapeutic targets for myeloid leukemias are eagerly awaited. Autophagy suppresses the development of cancer by maintaining cellular homeostasis; however, it also promotes cancer progression by helping cancer cells survive under various metabolic stresses. In addition, autophagy is promoted or suppressed in cancer cells by various genetic mutations. Therefore, the development of therapies that target autophagy is also being actively researched in the field of leukemia. In this review, studies of the role of autophagy in hematopoiesis, leukemogenesis, and myeloid leukemias are presented, and the impact of autophagy regulation on leukemia treatment and the clinical trials of autophagy-related drugs to date is discussed.
急性髓系白血病最重要的问题是预防复发和治疗复发。尽管缓解率提高到了大约 80%,但 5 年生存率仍只有 30%左右。造成这种情况的主要原因是复发率高,以及治疗选择有限。在慢性髓系白血病患者中,通过酪氨酸激酶抑制剂治疗达到一定时间的深度分子反应后,大约一半患者会达到无治疗缓解,但复发仍是一个问题。因此,髓系白血病的潜在治疗靶点备受期待。自噬通过维持细胞内稳态来抑制癌症的发展;然而,它也通过帮助癌细胞在各种代谢应激下存活来促进癌症的进展。此外,各种遗传突变促进或抑制癌细胞中的自噬。因此,靶向自噬的治疗方法的开发也在白血病领域得到了积极研究。本文综述了自噬在造血、白血病发生和髓系白血病中的作用,并讨论了自噬调控对白血病治疗的影响,以及迄今为止与自噬相关药物的临床试验。