These data suggest that MYC and BCL-2 may modulate the sensitivity to CHK1 inhibition in opposite ways: in fact, while high MYC expression could be associated with increased DDR activation and enhanced susceptibility to DDRi-induced DNA damage, overexpression of BCL-2 may significantly decrease the therapeutic activity of DDR inhibitors, providing mechanistic rationale of dual blockade of DDR and BCL-2 in DE and DH lymphomas. The gene discussed is CHEK1; the disease is lymphoma.