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Lack of allelic exclusion by secondary rearrangements of tumour B-cell receptor light chains in hairy cell leukaemia

Lack of allelic exclusion by secondary rearrangements of tumour B-cell receptor light chains in hairy cell leukaemia
Lack of allelic exclusion by secondary rearrangements of tumour B-cell receptor light chains in hairy cell leukaemia
Analyses of the tumour immunoglobulin (Ig) gene (IG) heavy (H) and light chains show heterogeneity of mutational status, but reveal common features of ongoing IGH isotype-switching with multiple IGH isotype expression and preference of IG lambda (IGL) light chain with selective use of IGLJ3. Phenotypic and immunogenetic analyses were performed in a series of 105 HCL patients to estimate prevalence of multiple IG light chain expression by the tumour cells. By phenotype, 3/105 HCL (2.9%) expressed double tumour-related Ig kappa (K) and L light chain proteins. By immunogenetic analysis, functional mutated double IGK(I) /IGK(II) , IGK(I) /IGL(I) and IGL(I) /IGL(II) transcripts were cloned and sequenced in 3/71 (4.2%) HCL. These latter three HCL expressed multiple IGH isotypes with mutated IGHVDJ rearrangements at the time of AID transcript expression. Most interestingly, the three cases had reinduced RAG1 transcript. In the double IGL expresser, single-cell analysis documented co-expression of the tumour-related IGLs in 5/6 cells (83%). In the IGK/IGL co-expresser, evidence of surface IgK/IgL isotype proteins confirmed functionality of the tumour-derived transcripts. The evidence of double light chain expression in single HCs and the new observation of RAG re-induction suggest ongoing selective influences on the BCR that may promote or maintain the HCL clone in the periphery.
hairy cell leukaemia, IG gene, secondary rearrangement, allelic exclusion, receptor revision
0278-0232
31-37
Sozzi, Elisa
e811ff23-6fe9-47ec-b052-fe8d34d1e36b
Amato, Teresa
1a4f6083-a38f-4ac0-ad5b-1cd628f6918b
Sahota, Surinder S.
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Nuti, Sandra
9a1ca48c-f4f0-4230-8a6f-05cf6fa31876
Raspadori, Donatella
185f6866-6d10-4f86-9add-72938cea80b3
Sicuranza, Anna
4ffad2b1-244f-4813-ac84-f573f8f44409
Cencini, Emanuele
3dc5d188-96b0-4f7d-abb8-af4d22638d7e
Tosi, Piero
ec48cb44-2815-438f-be28-30f1ca712945
Lauria, Francesco
f01f163b-abcb-4aad-b952-f4356692f519
Forconi, Francesco
ce9ed873-58cf-4876-bf3a-9ba1d163edc8
Sozzi, Elisa, Amato, Teresa, Sahota, Surinder S., Nuti, Sandra, Raspadori, Donatella, Sicuranza, Anna, Cencini, Emanuele, Tosi, Piero, Lauria, Francesco and Forconi, Francesco (2011) Lack of allelic exclusion by secondary rearrangements of tumour B-cell receptor light chains in hairy cell leukaemia Hematological Oncology, 29, (1), pp. 31-37. (doi:10.1002/hon.952). (PMID:20658474).

Sozzi, Elisa, Amato, Teresa, Sahota, Surinder S., Nuti, Sandra, Raspadori, Donatella, Sicuranza, Anna, Cencini, Emanuele, Tosi, Piero, Lauria, Francesco and Forconi, Francesco (2011) Lack of allelic exclusion by secondary rearrangements of tumour B-cell receptor light chains in hairy cell leukaemia Hematological Oncology, 29, (1), pp. 31-37. (doi:10.1002/hon.952). (PMID:20658474).

Record type: Article

Abstract

Analyses of the tumour immunoglobulin (Ig) gene (IG) heavy (H) and light chains show heterogeneity of mutational status, but reveal common features of ongoing IGH isotype-switching with multiple IGH isotype expression and preference of IG lambda (IGL) light chain with selective use of IGLJ3. Phenotypic and immunogenetic analyses were performed in a series of 105 HCL patients to estimate prevalence of multiple IG light chain expression by the tumour cells. By phenotype, 3/105 HCL (2.9%) expressed double tumour-related Ig kappa (K) and L light chain proteins. By immunogenetic analysis, functional mutated double IGK(I) /IGK(II) , IGK(I) /IGL(I) and IGL(I) /IGL(II) transcripts were cloned and sequenced in 3/71 (4.2%) HCL. These latter three HCL expressed multiple IGH isotypes with mutated IGHVDJ rearrangements at the time of AID transcript expression. Most interestingly, the three cases had reinduced RAG1 transcript. In the double IGL expresser, single-cell analysis documented co-expression of the tumour-related IGLs in 5/6 cells (83%). In the IGK/IGL co-expresser, evidence of surface IgK/IgL isotype proteins confirmed functionality of the tumour-derived transcripts. The evidence of double light chain expression in single HCs and the new observation of RAG re-induction suggest ongoing selective influences on the BCR that may promote or maintain the HCL clone in the periphery.

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More information

Published date: March 2011
Keywords: hairy cell leukaemia, IG gene, secondary rearrangement, allelic exclusion, receptor revision

Identifiers

Local EPrints ID: 179147
URI: http://eprints.soton.ac.uk/id/eprint/179147
ISSN: 0278-0232
PURE UUID: 5782d25b-2fae-4b8a-9a7f-ca31c60e1e85

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Date deposited: 31 Mar 2011 10:44
Last modified: 18 Jul 2017 12:03

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Contributors

Author: Elisa Sozzi
Author: Teresa Amato
Author: Sandra Nuti
Author: Donatella Raspadori
Author: Anna Sicuranza
Author: Emanuele Cencini
Author: Piero Tosi
Author: Francesco Lauria

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