Light-chain only multiple myeloma is due to the absence of functional (productive) rearrangement of the IgH gene at the DNA level

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. Us...

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Bibliographic Details
Published in:Blood 2004-05, Vol.103 (10), p.3869-3875
Main Authors: Magrangeas, Florence, Cormier, Marie-Laure, Descamps, Géraldine, Gouy, Nadège, Lodé, Laurence, Mellerin, Marie-Paule, Harousseau, Jean-Luc, Bataille, Régis, Minvielle, Stéphane, Avet-Loiseau, Hervé
Format: Article
Language:English
Subjects:
Alleles
Biological and medical sciences
Chromosomes, Human, Pair 14
Gene Rearrangement
Hematologic and hematopoietic diseases
Humans
Immunodeficiencies. Immunoglobulinopathies
Immunoglobulin Heavy Chains - genetics
Immunoglobulin Light Chains
Immunoglobulin Switch Region - genetics
Immunoglobulinopathies
Immunopathology
In Situ Hybridization, Fluorescence
Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis
Medical sciences
Multiple Myeloma - etiology
Multiple Myeloma - genetics
Multiple Myeloma - immunology
Recombination, Genetic
Translocation, Genetic
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Summary: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 secreting heavy chains (who presented a legitimate functional IgH rearrangement in every case), LC MM never displayed a functional IgH recombination. Interestingly, most LC MM cases presented one IgH allele with a germline configuration (including the DJ region), the second allele being usually involved in an illegitimate recombination. Of note, most of these translocations occurred close to (or at) switch regions, even though in some cases, breakpoints involving nonswitch regions were observed. Thus, this study clearly showed that LC MM is due to the absence of legitimate IgH rearrangement at the DNA level, reflecting possible abnormalities in the IgH gene recombinations during B-cell maturation. Furthermore, it showed that this defect did not prevent the activation of the switch process because most of 14q32 translocations observed in LC MM occurred at switch regions.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2003-07-2501