Istituto Superiore di Sanità, National Center for Drug Research and Evaluation, 00161 Rome, Italy.
Cells. 2023 Jun 5;12(11):1553. doi: 10.3390/cells12111553.
Autophagy is a highly conserved cellular degradation process that regulates cellular metabolism and homeostasis under normal and pathophysiological conditions. Autophagy and metabolism are linked in the hematopoietic system, playing a fundamental role in the self-renewal, survival, and differentiation of hematopoietic stem and progenitor cells, and in cell death, particularly affecting the cellular fate of the hematopoietic stem cell pool. In leukemia, autophagy sustains leukemic cell growth, contributes to survival of leukemic stem cells and chemotherapy resistance. The high frequency of disease relapse caused by relapse-initiating leukemic cells resistant to therapy occurs in acute myeloid leukemia (AML), and depends on the AML subtypes and treatments used. Targeting autophagy may represent a promising strategy to overcome therapeutic resistance in AML, for which prognosis remains poor. In this review, we illustrate the role of autophagy and the impact of its deregulation on the metabolism of normal and leukemic hematopoietic cells. We report updates on the contribution of autophagy to AML development and relapse, and the latest evidence indicating autophagy-related genes as potential prognostic predictors and drivers of AML. We review the recent advances in autophagy manipulation, combined with various anti-leukemia therapies, for an effective autophagy-targeted therapy for AML.
自噬是一种高度保守的细胞降解过程，可在正常和病理生理条件下调节细胞代谢和内稳态。自噬和代谢在造血系统中相互关联，在造血干细胞和祖细胞的自我更新、存活和分化以及细胞死亡中发挥着基本作用，特别是影响造血干细胞池的细胞命运。在白血病中，自噬维持白血病细胞的生长，有助于白血病干细胞的存活和化疗耐药性。急性髓系白血病（AML）中复发起始的对治疗有耐药性的白血病细胞导致疾病复发的频率很高，这取决于 AML 亚型和所使用的治疗方法。靶向自噬可能是克服 AML 治疗耐药性的一种有前途的策略，因为 AML 的预后仍然很差。在这篇综述中，我们说明了自噬的作用以及其失调对正常和白血病造血细胞代谢的影响。我们报告了自噬对 AML 发展和复发的贡献的最新进展，并提供了最新证据表明自噬相关基因是 AML 的潜在预后预测因子和驱动因素。我们综述了自噬操纵的最新进展，结合各种抗白血病疗法，为 AML 的有效自噬靶向治疗提供了依据。
