Abstract
The first-line drug Imatinib (IM) has achieved a curative effect in most chronic myeloid leukemia (CML) patients, but drug resistance remains a problem. More alternative therapeutic strategies need to explore. In recent years, targeting dysregulated DNA repair mechanisms provided promising options for cancer treatment. Here, we discovered the versatile Mediator of DNA Damage Checkpoint 1 (MDC1) interacted with γ-H2AX and 53BP1 in the early stage of the DNA damage response of cells. MDC1 overexpressed in CML cell lines and patients' bone marrow mononuclear cells. By knocking down MDC1, non-homologous end-joining pathways were mainly inhibited, leading to an intense accumulation of unrepaired intracellular DNA damage and an apparent cell apoptosis promotion. Notably, targeting MDC1 further enhanced drug sensitivity in IM-resistant CML cells. Our work revealed that MDC1 is a prospective target for CML treatment through regulating DNA damage repair mechanism, and also an alternative option for IM resistance dilemma. This study extends the understanding of regulating dysfunctional DNA repair mechanisms for cancer treatment.