Current advances in the role of classical non-homologous end joining in hematologic malignancies

Abstract

Background: Double-strand breaks (DSBs) are universally acknowledged as the most detrimental type of DNA damage, and their effective repair primarily depends on the non-homologous end joining (NHEJ) pathway. Such DSBs, which require NHEJ for resolution, can arise from intrinsic and extrinsic DNA-damaging factors or emerge naturally during essential biological processes like V(D)J recombination and antibody class switch recombination.

Main Body: Failure to properly repair DSBs may lead to genomic instability, disruption of cellular functions, and immunodeficiency, thereby promoting the development of hematologic malignancies. Conversely, overexpression of NHEJ-related genes can enhance resistance to DNA-damaging therapies in these cancers. Analyzing mutations in key classical NHEJ (cNHEJ) components and understanding their mechanisms could provide valuable biomarkers for predicting therapeutic outcomes and guiding treatment decisions. Consequently, defects in cNHEJ may offer insights into the development of novel drugs targeting DNA repair pathways.

Conclusion: We focus on genetic changes and alterations in gene regulation, while also providing an overview of cNHEJ.

Keywords

DNA damage repair / hematologic malignancies / leukaemia / lymphoma / myeloma / non-homologous end joining

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2025 The Author(s). Clinical and Translational Discovery published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.