Mesaros Oana, Onciul Madalina, Matei Emilia, Joldes Corina, Jimbu Laura, Neaga Alexandra, Serban Oana, Zdrenghea Mihnea, Nanut Ana Maria
Department of Hematology, Iuliu Hatieganu University of Medicine and Pharmacy, 8 Babes Str., 400012 Cluj-Napoca, Romania.
Department of Hematology, Ion Chiricuta Oncology Institute, 34-36 Republicii Str., 400015 Cluj-Napoca, Romania.
Biomedicines. 2024 Oct 11;12(10):2306. doi: 10.3390/biomedicines12102306.
Acute myeloid leukemia (AML) is a heterogenous malignant hemopathy, and although new drugs have emerged recently, current treatment options still show limited efficacy. Therapy resistance remains a major concern due to its contribution to treatment failure, disease relapse, and increased mortality among patients. The underlying mechanisms of resistance to therapy are not fully understood, and it is crucial to address this challenge to improve therapy. Macrophages are immune cells found within the bone marrow microenvironment (BMME), of critical importance for leukemia development and progression. One defining feature of macrophages is their plasticity, which allows them to adapt to the variations in the microenvironment. While this adaptability is advantageous during wound healing, it can also be exploited in cancer scenarios. Thus, clinical and preclinical investigations that target macrophages as a therapeutic strategy appear promising. Existing research indicates that targeting macrophages could enhance the effectiveness of current AML treatments. This review addresses the importance of macrophages as therapeutic targets including relevant drugs investigated in clinical trials such as pexidartinib, magrolimab or bexmarilimab, but also provides new insights into lesser-known therapies, like macrophage receptor with a collagenous structure (MACRO) inhibitors and Toll-like receptor (TLR) agonists.
急性髓系白血病（AML）是一种异质性恶性血液病，尽管近年来出现了新药，但目前的治疗方案疗效仍然有限。治疗耐药性仍是一个主要问题，因为它会导致治疗失败、疾病复发以及患者死亡率增加。治疗耐药的潜在机制尚未完全明确，应对这一挑战对于改善治疗至关重要。巨噬细胞是骨髓微环境（BMME）中的免疫细胞，对白血病的发生和发展至关重要。巨噬细胞的一个显著特征是其可塑性，这使其能够适应微环境的变化。虽然这种适应性在伤口愈合过程中是有利的，但在癌症情况下也可能被利用。因此，将巨噬细胞作为治疗策略的临床和临床前研究似乎很有前景。现有研究表明，靶向巨噬细胞可以提高当前AML治疗的有效性。本综述阐述了巨噬细胞作为治疗靶点的重要性，包括在临床试验中研究的相关药物，如培西达替尼、马罗利单抗或贝克斯马利单抗，同时也为鲜为人知的疗法提供了新见解，如具有胶原结构的巨噬细胞受体（MACRO）抑制剂和Toll样受体（TLR）激动剂。
