Pathogenesis of PML is uncertain, probably related to reactivation of the virus in a setting of altered immune surveillance: while brentuximab causes CD30+ activated T-cells depletion, rituximab does not result in T-lymphocyte depletion and PML may result from expansion of pre-B-lymphocytes harboring latent JC virus after rituximab mediated B-lymphocyte depletion (50, 51). The gene discussed is TNFRSF8; the disease is progressive multifocal leukoencephalopathy.