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

Abstract

Multiple myeloma (MM) is closely associated with abnormal DNA repair and genome instability. The bone marrow microenvironment, particularly myeloma associated macrophages (MΦs) is critical to the progression of MM. However, there is limited understanding on the role of MΦs in DNA repair in MM. Here, we found that MΦs regulated DNA repair in MM cells by the CXCL5/8-CXCR2 axis. By promoting non-homologous end joining rather than homology-directed repair, MΦs increased the probability of chromosomal translocations in MM cells. Furthermore, clinical data confirmed that MΦs are closely associated to the increased genetic variations of MM patients' primary cells. The study elucidates a mechanism by which MΦs regulates DNA repair in MM in the microenvironment and provides a potentially new target to counter MM progression.