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. 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.
Magrangeas
Florence
F
Laboratory of Hematology, Clinical Hematology Department, University Hospital, Nantes, France.
Cormier
Marie-Laure
ML
Descamps
Géraldine
G
Gouy
Nadège
N
Lodé
Laurence
L
Mellerin
Marie-Paule
MP
Harousseau
Jean-Luc
JL
Bataille
Régis
R
Minvielle
Stéphane
S
Avet-Loiseau
Hervé
H
D000483:Alleles; D002883:Chromosomes, Human, Pair 14; D015321:Gene Rearrangement; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007147:Immunoglobulin Light Chains; D007134:Immunoglobulin Switch Region / Q000235:genetics; D017404:In Situ Hybridization, Fluorescence; D009101:Multiple Myeloma / Q000209:etiology / Q000235:genetics* / Q000276:immunology; D011995:Recombination, Genetic; D014178:Translocation, Genetic
D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains