Macrophages promote aberrant DNA repair in multiple myeloma via the CXCL5/8-CXCR2 axis.

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.