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Selective influences in the expressed immunoglobulin heavy and light chain gene repertoire in hairy cell leukemia

Selective influences in the expressed immunoglobulin heavy and light chain gene repertoire in hairy cell leukemia
Selective influences in the expressed immunoglobulin heavy and light chain gene repertoire in hairy cell leukemia
Background: we previously reported ongoing mutational and isotype switch events in the immunoglobulin (Ig) heavy chain (H) locus in hairy cell leukemia. Those analyses raised questions on the incidence and type of selective influences occurring on the tumor B-cell receptor of hairy cell leukemia.

Design and methods: to further investigate this issue, we examined the full IGH and {kappa} and {lambda} light chains (IG{kappa} and IG{lambda}) variable and constant region transcripts expressed in a large cohort of patients with hairy cell leukemia (n=88).

Results: multiple IgH isotypes were expressed in 46/56 (82%) cases of hairy cell leukemia. Comparison of tumor with normal B-cell repertoires revealed preferential usage of IGHV3-21, IGHV3-30 and IGHV3-33 in hairy cell leukemia (p=0.001, p=0.003 and p=0.001, respectively). Light chain analysis demonstrated preferential Igl use with an inverted IGk:IGl ratio (0.7:1) and universal usage of IGLJ3. Analysis of LCDR3 junctions revealed highly homologous motifs in 40% of IGL. Parallel analysis of IGH and IGL showed selective pairing of IGHV3-21/30/33 segments to specific LCDR3-J3 subsets (p=0.008). Of 40 cases of hairy cell leukemia, 38 had mutated IGHV and/or IGK/LV, with variations in 13/13 cloned cases, while two had 100% unmutated IGHV and IGK/LV.

Conclusions: overall, biased IGV usage, preference for Ig{lambda} with universal IGLJ3 usage and a high incidence of LCDR3 homologous motifs suggest selective influences on the B-cell receptor of hairy cell leukemia. Ongoing mutations and isotype switching suggest that influences occur on the tumor B-cell receptor at ectopic sites
hairy cell leukemia, immunoglobulin, IGH, IGL, IGK, heavy chain, light chain
0390-6078
697-705
Forconi, Francesco
ce9ed873-58cf-4876-bf3a-9ba1d163edc8
Sozzi, Elisa
e811ff23-6fe9-47ec-b052-fe8d34d1e36b
Rossi, Davide
b4b2506d-794c-4c79-8b2d-6767554fd52a
Sahota, Surinder S
66c1457f-cba2-4c49-9c8c-fcee0748b6b8
Amato, Teresa
1a4f6083-a38f-4ac0-ad5b-1cd628f6918b
Raspadori, Donatella
185f6866-6d10-4f86-9add-72938cea80b3
Trentin, Livio
457595df-2d40-4392-931c-3919eb5620ec
Leoncini, Lorenzo
ba95251c-885b-4881-b8fd-119bca42e9c2
Gaidano, Gianluca
1a6a7107-107b-4891-82e0-5fedadd2f65a
Lauria, Francesco
f01f163b-abcb-4aad-b952-f4356692f519
Forconi, Francesco
ce9ed873-58cf-4876-bf3a-9ba1d163edc8
Sozzi, Elisa
e811ff23-6fe9-47ec-b052-fe8d34d1e36b
Rossi, Davide
b4b2506d-794c-4c79-8b2d-6767554fd52a
Sahota, Surinder S
66c1457f-cba2-4c49-9c8c-fcee0748b6b8
Amato, Teresa
1a4f6083-a38f-4ac0-ad5b-1cd628f6918b
Raspadori, Donatella
185f6866-6d10-4f86-9add-72938cea80b3
Trentin, Livio
457595df-2d40-4392-931c-3919eb5620ec
Leoncini, Lorenzo
ba95251c-885b-4881-b8fd-119bca42e9c2
Gaidano, Gianluca
1a6a7107-107b-4891-82e0-5fedadd2f65a
Lauria, Francesco
f01f163b-abcb-4aad-b952-f4356692f519

Forconi, Francesco, Sozzi, Elisa, Rossi, Davide, Sahota, Surinder S, Amato, Teresa, Raspadori, Donatella, Trentin, Livio, Leoncini, Lorenzo, Gaidano, Gianluca and Lauria, Francesco (2008) Selective influences in the expressed immunoglobulin heavy and light chain gene repertoire in hairy cell leukemia. Haematologica, 93 (5), 697-705. (doi:10.3324/haematol.12282). (PMID:18387977)

Record type: Article

Abstract

Background: we previously reported ongoing mutational and isotype switch events in the immunoglobulin (Ig) heavy chain (H) locus in hairy cell leukemia. Those analyses raised questions on the incidence and type of selective influences occurring on the tumor B-cell receptor of hairy cell leukemia.

Design and methods: to further investigate this issue, we examined the full IGH and {kappa} and {lambda} light chains (IG{kappa} and IG{lambda}) variable and constant region transcripts expressed in a large cohort of patients with hairy cell leukemia (n=88).

Results: multiple IgH isotypes were expressed in 46/56 (82%) cases of hairy cell leukemia. Comparison of tumor with normal B-cell repertoires revealed preferential usage of IGHV3-21, IGHV3-30 and IGHV3-33 in hairy cell leukemia (p=0.001, p=0.003 and p=0.001, respectively). Light chain analysis demonstrated preferential Igl use with an inverted IGk:IGl ratio (0.7:1) and universal usage of IGLJ3. Analysis of LCDR3 junctions revealed highly homologous motifs in 40% of IGL. Parallel analysis of IGH and IGL showed selective pairing of IGHV3-21/30/33 segments to specific LCDR3-J3 subsets (p=0.008). Of 40 cases of hairy cell leukemia, 38 had mutated IGHV and/or IGK/LV, with variations in 13/13 cloned cases, while two had 100% unmutated IGHV and IGK/LV.

Conclusions: overall, biased IGV usage, preference for Ig{lambda} with universal IGLJ3 usage and a high incidence of LCDR3 homologous motifs suggest selective influences on the B-cell receptor of hairy cell leukemia. Ongoing mutations and isotype switching suggest that influences occur on the tumor B-cell receptor at ectopic sites

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More information

Published date: 1 May 2008
Keywords: hairy cell leukemia, immunoglobulin, IGH, IGL, IGK, heavy chain, light chain
Organisations: Faculty of Medicine

Identifiers

Local EPrints ID: 73011
URI: http://eprints.soton.ac.uk/id/eprint/73011
ISSN: 0390-6078
PURE UUID: 030c555e-226c-48e8-ad8f-9e6ef1832ea2

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Date deposited: 02 Mar 2010
Last modified: 20 Sep 2018 16:31

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Contributors

Author: Elisa Sozzi
Author: Davide Rossi
Author: Surinder S Sahota
Author: Teresa Amato
Author: Donatella Raspadori
Author: Livio Trentin
Author: Lorenzo Leoncini
Author: Gianluca Gaidano
Author: Francesco Lauria

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