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...

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Main Authors: Pengcheng Liu, Zizhen Xu
Format: Article
Language:English
Published: Wiley 2025-06-01
Series:Clinical and Translational Discovery
Subjects:
Online Access:https://doi.org/10.1002/ctd2.70053
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author Pengcheng Liu
Zizhen Xu
author_facet Pengcheng Liu
Zizhen Xu
author_sort Pengcheng Liu
collection DOAJ
description 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.
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spelling doaj-art-42970b3866f946df845aecfd5bc539052025-08-20T02:20:52ZengWileyClinical and Translational Discovery2768-06222025-06-0153n/an/a10.1002/ctd2.70053Current advances in the role of classical non‐homologous end joining in hematologic malignanciesPengcheng Liu0Zizhen Xu1Department of Laboratory Medicine College of Health Science and Technology Ruijin Hospital, Shanghai Jiao Tong University School of Medicine Shanghai ChinaDepartment of Laboratory Medicine College of Health Science and Technology Ruijin Hospital, Shanghai Jiao Tong University School of Medicine Shanghai ChinaAbstract 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.https://doi.org/10.1002/ctd2.70053DNA damage repairhematologic malignanciesleukaemialymphomamyelomanon‐homologous end joining
spellingShingle Pengcheng Liu
Zizhen Xu
Current advances in the role of classical non‐homologous end joining in hematologic malignancies
Clinical and Translational Discovery
DNA damage repair
hematologic malignancies
leukaemia
lymphoma
myeloma
non‐homologous end joining
title Current advances in the role of classical non‐homologous end joining in hematologic malignancies
title_full Current advances in the role of classical non‐homologous end joining in hematologic malignancies
title_fullStr Current advances in the role of classical non‐homologous end joining in hematologic malignancies
title_full_unstemmed Current advances in the role of classical non‐homologous end joining in hematologic malignancies
title_short Current advances in the role of classical non‐homologous end joining in hematologic malignancies
title_sort current advances in the role of classical non homologous end joining in hematologic malignancies
topic DNA damage repair
hematologic malignancies
leukaemia
lymphoma
myeloma
non‐homologous end joining
url https://doi.org/10.1002/ctd2.70053
work_keys_str_mv AT pengchengliu currentadvancesintheroleofclassicalnonhomologousendjoininginhematologicmalignancies
AT zizhenxu currentadvancesintheroleofclassicalnonhomologousendjoininginhematologicmalignancies