Preferential Expression of Human λ-Light-Chain Variable-Region Subgroups in Multiple Myeloma, AL Amyloidosis, and Waldenström's Macroglobulinemia

Ozaki, Shuji; Abe, Masahiro; Wolfenbarger, D; Weiss, Deborah; Solomon, Alan

doi:10.1006/clin.1994.1070

Cited by 68 publications

(47 citation statements)

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“…Not only are these genes the most commonly observed in AL S , but they and their gene families are also conspicuously more common in AL S than in the normal B-repertoire. 21,23,24 In contrast, the distribution of IGVL genes and families for patients with AL L was very similar to that seen in the normal B-cell repertoire, with LV6 found less commonly and the KV3 family (and the KV3-20 gene in particular) more commonly. 8 The potential mechanisms underlying the differences between IGVL gene usage in AL S, AL L , nonamyloidogenic plasma cell dyscrasias, and normal controls are not clear.…”

Section: Discussionmentioning

confidence: 69%

Clarifying immunoglobulin gene usage in systemic and localized immunoglobulin light-chain amyloidosis by mass spectrometry

Kourelis¹,

Dasari²,

Theis³

et al. 2017

Blood

117

106

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Section: Discussionmentioning

confidence: 69%

Clarifying immunoglobulin gene usage in systemic and localized immunoglobulin light-chain amyloidosis by mass spectrometry

Kourelis¹,

Dasari²,

Theis³

et al. 2017

Blood

117

106

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“…Subsequent work using protein sequencing unequivocally demonstrated that virtually all VI monoclonal light chains isolated so far are from amyloidosis patients. By means of ELISA typing with monoclonal antibodies to the various families, Ozaki and colleagues 7 established that the prevalence of VI light chains in amyloidosis could reach 30%, whereas VI light chains are barely found in normal serum (5%). Our report is in line with the results of these studies and confirms the rarity of polyclonal plasma cells expressing VI light chains (2.3%).…”

Section: Figure 5 Somatic Mutations In Amyloid and Polyclonal V Regimentioning

confidence: 99%

“…2,5 These observations suggest the existence of V genes with a propensity to form amyloid (amyloidogenic). Indeed, light-chain protein sequencing 6 and enzyme-linked immunosorbent assay (ELISA) typing 7 showed a very high prevalence of VI family light chains in amyloidosis and a strong association with this disorder: with rare exceptions, VI monoclonal light chains are found only in patients with AL. Since this seminal observation, no other amyloid-associated genes have been identified.…”

Section: Introductionmentioning

confidence: 99%

Analysis of Vλ-Jλ expression in plasma cells from primary (AL) amyloidosis and normal bone marrow identifies 3r(λIII) as a new amyloid-associated germline gene segment

Perfetti

Casarini

Palladini

et al. 2002

Blood

152

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Primary (AL) amyloidosis is a plasma cell dyscrasia characterized by extracellular deposition of monoclonal light-chain variable region (V) fragments in the form of amyloid fibrils. Light-chain amyloid is rare, and it is not fully understood why it occurs in only a fraction of patients with a circulating monoclonal component and why it typically associates with isotype and VI family light-chain proteins. To provide insights into these issues, we obtained complete nucleotide sequences of monoclonal V regions from 55 consecutive unselected cases of primary amyloidosis and the results were compared with the light-chain expression profile of polyclonal marrow plasma cells from 3 healthy donors (a total of 264 sequences). We demonstrated that: (1) the III family is the most frequently used both in amyloidosis (47%) and in polyclonality (43%); (2) both conditions are characterized by gene restriction; (3) a very skewed repertoire is a feature of amyloidosis, because just 2 germline genes belonging to the III and VI families, namely 3r (22% of cases, III) and 6a (20%, VI), contributed equally to encode 42% of amyloid V regions; (4) these same 2 gene segments have a strong association with amyloidosis if their prevalences are compared with those in polyclonal conditions (3r, 8.3%, P ‫؍‬ .024; 6a, 2.3%, P ‫؍‬ .0008, 2 test); (5) the J 2/3 segment, encoding the fourth framework region, appears to be slightly overrepresented in AL (83% versus 67%, P ‫؍‬ .03), and this might be related to preferential J 2/3 rearrangement in amyloid (11 of 12 cases) versus polyclonal 3r light chains (13 of 22 cases). These findings demonstrate that V -J expression is more restricted in plasma cells from amyloidosis than from polyclonal bone marrow and identify 3r as a new disease-associated gene segment. Overusage of just 2 gene segments, 3r and 6a, can thus account for the light-chain overrepresentation typical of this disorder. (Blood. 2002;100: 948-953)

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“…Both k-and l-chains are represented, l-chains being more commonly found in amyloids [3]. Most subgroups are known to be amyloidogenic but lVI is strongly over-represented since all lVI proteins that have been characterized hitherto have been associated with amyloid deposits [4,5]. In systemic amyloidosis a clone of plasma cells, benign or malignant, is producing the AL-protein precursor, which is carried around with the blood.…”

Section: Introductionmentioning

confidence: 99%

Constant Region of a κ III Immunoglobulin Light Chain as a Major AL‐Amyloid Protein

et al. 1998

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Engvig JP, Olsen KE, Gislefoss RE, Sletten K, Wahlström O, Westermark P. Constant Region of a k III Immunoglobulin Light Chain as a Major AL-Amyloid Protein. Scand J Immunol 1998;48:92-98 AL-amyloidoses are generally described as a group of disorders in which N-terminal fragments of monoclonal immunoglobulin light chains are transferred into amyloid fibrils. We have, by amino acid sequence analyses and immunological methods, characterized the Bence-Jones protein and the corresponding AL protein as a k III immunoglobulin light chain from material of a patient with systemic AL-amyloidosis presenting as a local inguinal tumour. The two proteins showed some unique features. The major part of the AL amyloid fibril protein consisted of C-terminal fragments of the Bence-Jones protein. Furthermore, both the Bence-Jones protein and the AL protein were glycosylated, with possibly a glycosylation in the constant part of the light chain.

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Preferential Expression of Human λ-Light-Chain Variable-Region Subgroups in Multiple Myeloma, AL Amyloidosis, and Waldenström's Macroglobulinemia

Cited by 68 publications

References 0 publications

Clarifying immunoglobulin gene usage in systemic and localized immunoglobulin light-chain amyloidosis by mass spectrometry

Clarifying immunoglobulin gene usage in systemic and localized immunoglobulin light-chain amyloidosis by mass spectrometry

Analysis of Vλ-Jλ expression in plasma cells from primary (AL) amyloidosis and normal bone marrow identifies 3r(λIII) as a new amyloid-associated germline gene segment

Constant Region of a κ III Immunoglobulin Light Chain as a Major AL‐Amyloid Protein

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