Targeting N-cadherin (CDH2) and the malignant bone marrow microenvironment in acute leukaemia

• Published in: Expert reviews in molecular medicine Vol. 25; p. e16
• Main Authors: Parker, Jessica, Hockney, Sean, Blaschuk, Orest W, Pal, Deepali
• Format: Journal Article
• Language: English
• Published: England 03-05-2023
• Subjects: Antigens, CD - metabolism; Antigens, CD - therapeutic use; Bone Marrow - metabolism; Bone Marrow - pathology; Cadherins - genetics; Cadherins - metabolism; Cadherins - therapeutic use; Cell Adhesion; Child; Humans; Leukemia, Myeloid, Acute - drug therapy; Leukemia, Myeloid, Acute - therapy; Neoplasm Recurrence, Local - metabolism; Neoplasm Recurrence, Local - pathology; Tumor Microenvironment; leukaemia; cancer microenvironment; CDH2; Anti-cancer drugs; treatment resistance
• ISSN: 1462-3994
• 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.