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Multiple myeloma shows no intra-disease clustering of immunoglobulin heavy chain genes

Multiple myeloma shows no intra-disease clustering of immunoglobulin heavy chain genes
Multiple myeloma shows no intra-disease clustering of immunoglobulin heavy chain genes
Background: Characterization of the immunoglobulin gene repertoire has improved our understanding of the immunopathogenesis of lymphoid tumors. Early B-lymphocyte precursors of multiple myeloma are known to exist and might be susceptible to antigenic drive.

Design and Methods: To verify this hypothesis, we collected a database of 345 fully readable multiple myeloma immunoglobulin sequences. We characterized the immunoglobulin repertoire, analyzed the somatic hypermutation load, and investigated for stereotyped receptor clusters.

Results: Compared to the normal immunoglobulin repertoire, multiple myeloma displayed only modest differences involving only a few genes, showing that the myeloma immunoglobulin repertoire is the least skewed among mature B-cell tumors. Median somatic hypermutation load was 7.8%; median length of complementarity determining-region 3 was 15.5 amino acids. Clustering analysis showed the absence of myeloma specific clusters and no similarity with published chronic lymphocytic leukemia or lymphoma subsets.

Conclusions: Analysis of multiple myeloma immunoglobulin repertoire does not support a pathogenetic role for antigen selection in this tumor.
multiple myeloma, immunoglobulin, antigen selection, heavy chain gene
0390-6078
849-853
Ferrero, Simone
22a0ef9d-d391-4705-a4b1-4c6338dbdea0
Capello, Daniela
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Svaldi, Mirija
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Boi, Michela
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Gatti, Daniela
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Drandi, Daniela
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Rossi, Davide
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Barbiero, Sara
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Mantoan, Barbara
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Mantella, Elisabetta
4d79b0f3-c797-45ba-a10e-f3f643a4dc62
Zanni, Manuela
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Ghione, Paola
0e52e0e3-421c-4da1-9961-ba8ce733e03d
Larocca, Alessandra
036e2887-cffd-4057-8418-f495110b74b3
Passera, Roberto
2b3e1b0e-37dc-4240-b025-f051030be847
Bertoni, Francesco
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Gattei, Valter
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Forconi, Francesco
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Laurenti, Luca
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Del Poeta, Giovanni
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Marasca, Roberto
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Cortelazzo, Sergio
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Gaidano, Gianluca
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Palumbo, Antonio
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Boccadoro, Mario
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Ladetto, Marco
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Ferrero, Simone
22a0ef9d-d391-4705-a4b1-4c6338dbdea0
Capello, Daniela
f4d381f4-aaa6-47ae-bebf-53b0aed65055
Svaldi, Mirija
c83a4de7-7b0c-49b8-9340-09a388428ab9
Boi, Michela
41825b3a-fb59-4196-bb65-e7de0fd151be
Gatti, Daniela
40ba74ae-4abf-436b-9041-bc9ce1fcd3ae
Drandi, Daniela
819ad430-52ed-4409-8e81-26a3b12d3adf
Rossi, Davide
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Barbiero, Sara
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Mantoan, Barbara
e3755f00-ad5c-4928-8648-24f78eea1015
Mantella, Elisabetta
4d79b0f3-c797-45ba-a10e-f3f643a4dc62
Zanni, Manuela
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Ghione, Paola
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Larocca, Alessandra
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Passera, Roberto
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Bertoni, Francesco
13297a2f-854a-4841-a410-d6bfca8afee8
Gattei, Valter
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Forconi, Francesco
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Laurenti, Luca
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Del Poeta, Giovanni
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Marasca, Roberto
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Cortelazzo, Sergio
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Gaidano, Gianluca
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Palumbo, Antonio
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Boccadoro, Mario
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Ladetto, Marco
eb383970-9337-4c08-818d-d77ce9884036

Ferrero, Simone, Capello, Daniela, Svaldi, Mirija, Boi, Michela, Gatti, Daniela, Drandi, Daniela, Rossi, Davide, Barbiero, Sara, Mantoan, Barbara, Mantella, Elisabetta, Zanni, Manuela, Ghione, Paola, Larocca, Alessandra, Passera, Roberto, Bertoni, Francesco, Gattei, Valter, Forconi, Francesco, Laurenti, Luca, Del Poeta, Giovanni, Marasca, Roberto, Cortelazzo, Sergio, Gaidano, Gianluca, Palumbo, Antonio, Boccadoro, Mario and Ladetto, Marco (2012) Multiple myeloma shows no intra-disease clustering of immunoglobulin heavy chain genes. Haematologica, 97 (6), 849-853. (doi:10.3324/haematol.2011.052852). (PMID:22207685)

Record type: Article

Abstract

Background: Characterization of the immunoglobulin gene repertoire has improved our understanding of the immunopathogenesis of lymphoid tumors. Early B-lymphocyte precursors of multiple myeloma are known to exist and might be susceptible to antigenic drive.

Design and Methods: To verify this hypothesis, we collected a database of 345 fully readable multiple myeloma immunoglobulin sequences. We characterized the immunoglobulin repertoire, analyzed the somatic hypermutation load, and investigated for stereotyped receptor clusters.

Results: Compared to the normal immunoglobulin repertoire, multiple myeloma displayed only modest differences involving only a few genes, showing that the myeloma immunoglobulin repertoire is the least skewed among mature B-cell tumors. Median somatic hypermutation load was 7.8%; median length of complementarity determining-region 3 was 15.5 amino acids. Clustering analysis showed the absence of myeloma specific clusters and no similarity with published chronic lymphocytic leukemia or lymphoma subsets.

Conclusions: Analysis of multiple myeloma immunoglobulin repertoire does not support a pathogenetic role for antigen selection in this tumor.

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More information

e-pub ahead of print date: 29 December 2011
Published date: 1 June 2012
Keywords: multiple myeloma, immunoglobulin, antigen selection, heavy chain gene
Organisations: Cancer Sciences

Identifiers

Local EPrints ID: 358109
URI: http://eprints.soton.ac.uk/id/eprint/358109
ISSN: 0390-6078
PURE UUID: 3da684ae-21d6-49c0-8277-e2da2699ccd0

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Date deposited: 04 Oct 2013 10:31
Last modified: 14 Mar 2024 15:00

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Contributors

Author: Simone Ferrero
Author: Daniela Capello
Author: Mirija Svaldi
Author: Michela Boi
Author: Daniela Gatti
Author: Daniela Drandi
Author: Davide Rossi
Author: Sara Barbiero
Author: Barbara Mantoan
Author: Elisabetta Mantella
Author: Manuela Zanni
Author: Paola Ghione
Author: Alessandra Larocca
Author: Roberto Passera
Author: Francesco Bertoni
Author: Valter Gattei
Author: Francesco Forconi
Author: Luca Laurenti
Author: Giovanni Del Poeta
Author: Roberto Marasca
Author: Sergio Cortelazzo
Author: Gianluca Gaidano
Author: Antonio Palumbo
Author: Mario Boccadoro
Author: Marco Ladetto

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