Multiple myeloma : illegitimate switch recombinations and their relation to chromosomal translocations

thelial system. The different environmental conditions, required by both treatment regimens to activate p53 and CD95, may indicate that lymphocyte apoptosis induced by these mechanisms involves a different phase. With regard to UVA-induced apoptosis, these 2 phases have previously been termed immediateand delayed-type apoptosis.8 The beneficial, clinical effects of ECP are thought not only to be due to the apoptosis induced in treated lymphocytes. ECP is believed also to induce a “vaccination-type” immunomodulatory response, whereby nontreated, but clonal T cells are also removed.9 In patients with cutaneous T-cell lymphoma (CTCL), ECP reduces the number of malignant CD41 T cells in “responders” while CD81 levels remain constant,10 a response we have also observed in patients with CTCL treated at Rotherham Photopheresis unit (P.T., unpublished data, December 2001). But in vivo chemotherapy causes a pan–T-cell depletion and lymphopenia.1 This difference may provide further evidence that the ECP effect is not purely linked to the induction of T-cell apoptosis. Monocytes do not become apoptotic following ECP.7 Conversely, ECP-treated monocytes demonstrate increased secretion of TNFa,11 enhanced ability to phagocytose apoptotic T cells,7 and unlike with other UV therapies, retain the adhesion markers required for the presentation of processed antigens to T cells (J.B., P.T., manuscript submitted, November 2001). The similar mechanisms, but differing outcomes, of the apoptosis induced by in vivo chemotherapy and ECP may help reinforce the importance of the monocytes in this immunomodulatory response. Further research may center on the manipulation of these antigen-presenting cells as a useful tool in the treatment of other clonal conditions. John Bladon and Peter Taylor