Department of Medicine V, Hematology, Oncology and Rheumatology, University Hospital Heidelberg, Heidelberg, Germany.
University of Heidelberg Medical Faculty, Heidelberg, Germany.
Int J Cancer. 2024 Jan 15;154(2):197-209. doi: 10.1002/ijc.34684. Epub 2023 Aug 11.
The expansion of acute myeloid leukemia (AML) blasts not only suppresses normal hematopoiesis, but also alters the microenvironment. The interplay of different components of the bone marrow gives rise to altered metabolic states and activates signaling pathways which lead to resistance and impede effective therapy. Therefore, the underlying processes and mechanisms represent attractive therapeutic leverage points for overcoming therapy resistance in AML. Here, we briefly discuss resistance mechanisms based on cell interactions and secreted soluble factors in the hematopoietic niche and provide an overview of niche-related therapeutic targets currently undergoing preclinical and clinical investigation which may help improve the outcome in AML therapy.
急性髓系白血病 (AML) blasts 的扩增不仅抑制了正常造血,还改变了微环境。骨髓中不同成分的相互作用导致代谢状态的改变,并激活信号通路,导致耐药性并阻碍有效治疗。因此,这些潜在的过程和机制为克服 AML 中的治疗耐药性提供了有吸引力的治疗杠杆点。在这里,我们简要讨论了基于造血龛中细胞相互作用和分泌的可溶性因子的耐药机制,并概述了目前正在进行临床前和临床研究的与龛相关的治疗靶点,这些靶点可能有助于改善 AML 治疗的结果。