Multiple myeloma : illegitimate switch recombinations and their relation to chromosomal translocations
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چکیده
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constant,10 a response we have also observed in patients with CTCL treated at Rotherham Photopheresis unit (P.T., unpublished data, December 2001).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
منابع مشابه
Multiple myeloma: illegitimate switch recombinations and their relation to chromosomal translocations.
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Illegitimate switch recombinations are present in approximately half of primary myeloma tumors, but do not relate to known prognostic indicators or survival.
The myeloma plasma cell is a postgerminal center, isotype-switched B cell. Chromosomal translocations into immunoglobulin heavy chain (IgH) switch regions, recombination sites in isotype switching, were initially demonstrated in myeloma cell lines but only a limited number of primary tumors. Molecular cytogenetics have since been applied to a series of primary tumors, in which IgH translocation...
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Although most multiple myeloma (MM) cases are characterized by the detection of a monoclonal immunoglobulin in the serum, about 15% of the patients present only immunoglobulin light chains, detected either in the urine or serum or both. These patients are designated as having light-chain (LC) MM. Using fiber-fluorescent in situ hybridization, and in contrast to patients and myeloma cell lines s...
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To elucidate the mechanisms underlying chromosomal translocations in diffuse large B cell lymphoma (DLBCL), we investigated the nature and extent of immunoglobulin class switch recombination (CSR) in these tumors. We used Southern blotting to detect legitimate and illegitimate CSR events in tumor samples of the activated B cell-like (ABC), germinal center B cell-like (GCB), and primary mediasti...
متن کاملHigh incidence of translocations t(11;14)(q13;q32) and t(4;14)(p16;q32) in patients with plasma cell malignancies.
Abnormalities involving the 14q32 region are recurrent chromosomal changes in plasma cell malignancies. Recent preliminary molecular analyses found IGH rearrangements in almost 100% of human myeloma cell lines and in 75% of patients. However, no systematic study analyzing the nature of the partner chromosomal regions have been reported thus far. To define the exact incidence of illegitimate IGH...
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