Department of Applied Sciences, Northumbria University, Newcastle upon Tyne NE1 8ST, UK.
Zonula Incorporated, Kirkland, QC H9J 2X2, Canada.
Expert Rev Mol Med. 2023 May 3;25:e16. doi: 10.1017/erm.2023.13.
This review discusses current research on acute paediatric leukaemia, the leukaemic bone marrow (BM) microenvironment and recently discovered therapeutic opportunities to target leukaemia-niche interactions. The tumour microenvironment plays an integral role in conferring treatment resistance to leukaemia cells, this poses as a key clinical challenge that hinders management of this disease. Here we focus on the role of the cell adhesion molecule N-cadherin (CDH2) within the malignant BM microenvironment and associated signalling pathways that may bear promise as therapeutic targets. Additionally, we discuss microenvironment-driven treatment resistance and relapse, and elaborate the role of CDH2-mediated cancer cell protection from chemotherapy. Finally, we review emerging therapeutic approaches that directly target CDH2-mediated adhesive interactions between the BM cells and leukaemia cells.
本文综述了急性儿科白血病、白血病骨髓（BM）微环境以及最近发现的靶向白血病-龛位相互作用的治疗机会的研究进展。肿瘤微环境在赋予白血病细胞治疗抵抗方面起着重要作用，这是一个关键的临床挑战，阻碍了这种疾病的治疗。在这里，我们重点关注细胞黏附分子 N-钙黏蛋白（CDH2）在恶性 BM 微环境中的作用以及相关信号通路，这些通路可能是有希望的治疗靶点。此外，我们还讨论了微环境驱动的治疗抵抗和复发，并阐述了 CDH2 介导的癌细胞对化疗的保护作用。最后，我们综述了直接靶向 BM 细胞与白血病细胞之间 CDH2 介导的黏附相互作用的新兴治疗方法。
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