Related Experiment Video
Updated: Sep 18, 2025
Development of an Insert Co-culture System of Two Cellular Types in the Absence of Cell-Cell Contact
Published on: July 17, 2016
Macrophages promote aberrant DNA repair in multiple myeloma via the CXCL5/8-CXCR2 axis
Mengmeng Dong1, Donghua He2, Jinna Zhang1
1Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, No.79 Qingchun Rd, Hangzhou! Zhejiang, 310003, China; Institute of Translational Medicine, Zhejiang University School of Medicine and Zhejiang University Cancer Center, Hangzhou, Zhejiang 310029.
Abstract:
Multiple myeloma (MM) is closely associated with abnormal DNA repair and genome instability. The bone marrow microenvironment, particularly myeloma-associated macrophages (MΦ), is critical to the progression of MM. However, there is limited understanding on the role of MΦ in DNA repair in MM. Here, we found that MΦ regulated DNA repair in MM cells by the CXCL5/8-CXCR2 axis. By promoting non-homologous end joining rather than homology-directed repair, MΦ increased the probability of chromosomal translocations in MM cells. Furthermore, clinical data confirmed that MΦ are closely associated to the increased genetic variations of MM patients' primary cells. The study elucidates a mechanism by which MΦ regulate DNA repair in MM in the microenvironment and provides a potentially new target to counter MM progression.
Insights
Myeloma associated macrophages (MΦs) promote DNA repair in multiple myeloma (MM) cells, increasing chromosomal translocations. Targeting the CXCL5/8-CXCR2 axis offers a new strategy against MM progression.
Area of Science:
- Oncology
- Immunology
- Genetics
Background:
- Multiple myeloma (MM) exhibits abnormal DNA repair and genome instability.
- Myeloma associated macrophages (MΦs) in the bone marrow microenvironment are crucial for MM progression.
- The specific role of MΦs in MM DNA repair remains poorly understood.
Purpose of the Study:
- To investigate the mechanism by which MΦs influence DNA repair in multiple myeloma cells.
- To identify the molecular pathways involved in MΦ-mediated DNA repair regulation in MM.
- To explore MΦs as a potential therapeutic target for MM.
Main Methods:
- Analysis of the CXCL5/8-CXCR2 signaling axis in MM cells and MΦs.
- Assessment of DNA repair pathway preference (non-homologous end joining vs. homology-directed repair) in MM cells co-cultured with MΦs.
- Evaluation of chromosomal translocations in MM cells.
- Correlation of MΦ presence with genetic variations in primary MM patient cells.
Main Results:
- MΦs regulate DNA repair in MM cells via the CXCL5/8-CXCR2 axis.
- MΦs promote non-homologous end joining over homology-directed repair in MM cells.
- This shift in DNA repair increases the likelihood of chromosomal translocations in MM cells.
- Clinical data show a correlation between MΦs and increased genetic variations in MM patients.
Conclusions:
- MΦs play a significant role in regulating DNA repair and genomic instability in the MM microenvironment.
- The CXCL5/8-CXCR2 axis is a key mediator of MΦ-driven DNA repair in MM.
- Targeting MΦs or this axis presents a novel therapeutic strategy for multiple myeloma.
Related Concept Videos
02:23Abnormal Proliferation
01:38Nucleotide Excision Repair
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
01:15Differentiation of Common Myeloid Progenitor Cells
01:20Mismatch Repair
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...