Given that JMJD1B deficiency increases sensitivity to PARP1 inhibition, our results suggest a potential new mechanism by which synthetic lethality is induced for cancer treatment by coupling JMJD1B gene deficiency (e.g., 5q syndrome) or LIG1 deficiency with PARP inhibitors. Here, KDM3B is linked to myelodysplastic syndrome associated with isolated del(5q).