Since HMGA2 has been known to promote RB cell proliferation and participate in the regulation of DNA damage response in cancer cells [21, 23, 24, 28], our findings altogether suggest that DOT1L inhibition has a dual role in chemosensitization of RB cells by directly impairing the early DNA damage response mediated by DOT1L itself upon genotoxic insults, and also by downregulating the expression of HMGA2 as a rather late effect of DOT1L inhibition. The gene discussed is HMGA2; the disease is cancer.