A molecular basis for nonsecretory myeloma.
The biosynthesis of aberrant immunoglobulin polypeptides by monoclonal plasma cells has been implicated in the pathogenesis of nonsecretory myeloma. Our studies of a patient with this disorder indeed have demonstrated the presence of abnormal kappa light chains that resulted from a frameshift mutation in nucleotides encoding the constant region of the molecule. As a consequence of a 2-base deletion in codon 187 and loss of the normal stop codon, this portion of the kappa chain was composed of 128 amino acids (rather than the expected 106), with a completely anomalous sequence after position 187 that included absence of the cysteines required for intrachain and interchain disulfide bonds. The unusual primary structure of this component was confirmed by mass spectrometric and amino acid sequence analyses of cytoplasmic protein extracts. Our studies provide the first evidence that human nonsecretory myeloma may result from an alteration in the light-chain constant region.
Coriu
Daniel
D
Human Immunology and Cancer Program, Department of Medicine, University of Tennessee Graduate School of Medicine, Knoxville, TN 37920, USA.
Weaver
Kristal
K
Schell
Maria
M
Eulitz
Manfred
M
Murphy
Charles L
CL
Weiss
Deborah T
DT
Solomon
Alan
A
D000595:Amino Acid Sequence; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007147:Immunoglobulin Light Chains / Q000737:chemistry / Q000235:genetics; D007075:Immunoglobulin M / Q000097:blood; D007145:Immunoglobulin kappa-Chains / Q000737:chemistry / Q000235:genetics; D008969:Molecular Sequence Data; D009101:Multiple Myeloma / Q000097:blood / Q000235:genetics* / Q000276:immunology / Q000652:urine; D012334:RNA, Neoplasm / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007147:Immunoglobulin Light Chains; D007075:Immunoglobulin M; D007145:Immunoglobulin kappa-Chains; D012334:RNA, Neoplasm