PML and myeloid sarcoma: Risk factors in patients with multiple sclerosis (MS) are seropositivity for JC virus, prior treatment with immunosuppressants, and duration of natalizumab treatment, with the highest incidence occurring after 24 monthly doses.1 However, patients with MS with no natalizumab treatment and patients with other disorders with similar histories of immunosuppression and JV virus seropositivity have much lower PML risks, suggesting something specific to natalizumab effects on downstream pathways that results in JC viral activation and PML.