Jain Vaibhav, Bose Swaroop, Arya Awadhesh K, Arif Tasleem
Abramson Cancer Center, Department of Medicine, 421 Curie Blvd., Philadelphia, PA 19104, USA.
Department of Dermatology, Mount Sinai Icahn School of Medicine, New York, NY 10029, USA.
Cancers (Basel). 2022 Mar 23;14(7):1618. doi: 10.3390/cancers14071618.
Lysosomes are cellular organelles that regulate essential biological processes such as cellular homeostasis, development, and aging. They are primarily connected to the degradation/recycling of cellular macromolecules and participate in cellular trafficking, nutritional signaling, energy metabolism, and immune regulation. Therefore, lysosomes connect cellular metabolism and signaling pathways. Lysosome's involvement in the critical biological processes has rekindled clinical interest towards this organelle for treating various diseases, including cancer. Recent research advancements have demonstrated that lysosomes also regulate the maintenance and hemostasis of hematopoietic stem cells (HSCs), which play a critical role in the progression of acute myeloid leukemia (AML) and other types of cancer. Lysosomes regulate both HSCs' metabolic networks and identity transition. AML is a lethal type of blood cancer with a poor prognosis that is particularly associated with aging. Although the genetic landscape of AML has been extensively described, only a few targeted therapies have been produced, warranting the need for further research. This review summarizes the functions and importance of targeting lysosomes in AML, while highlighting the significance of lysosomes in HSCs maintenance.
溶酶体是调节细胞内稳态、发育和衰老等重要生物学过程的细胞器。它们主要与细胞大分子的降解/再循环相关，并参与细胞运输、营养信号传导、能量代谢和免疫调节。因此，溶酶体连接着细胞代谢和信号通路。溶酶体参与关键生物学过程，这重新点燃了临床上对该细胞器治疗包括癌症在内的各种疾病的兴趣。最近的研究进展表明，溶酶体还调节造血干细胞（HSC）的维持和止血，而造血干细胞在急性髓系白血病（AML）和其他类型癌症的进展中起着关键作用。溶酶体调节造血干细胞的代谢网络和身份转变。AML是一种预后不良的致命性血癌，尤其与衰老相关。尽管AML的基因图谱已被广泛描述，但仅产生了少数靶向治疗方法，因此有必要进行进一步研究。本综述总结了在AML中靶向溶酶体的功能和重要性，同时强调了溶酶体在造血干细胞维持中的重要性。
