Lack of allelic exclusion by secondary rearrangements of tumour B-cell receptor light chains in hairy cell leukaemia
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), 31-37. (doi:10.1002/hon.952). (PMID:20658474).
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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.
|Digital Object Identifier (DOI):||doi:10.1002/hon.952|
|Keywords:||hairy cell leukaemia, IG gene, secondary rearrangement, allelic exclusion,receptor revision|
|Subjects:||R Medicine > RA Public aspects of medicine
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
|Divisions:||University Structure - Pre August 2011 > School of Medicine > Cancer Sciences
|Date Deposited:||31 Mar 2011 10:44|
|Last Modified:||27 Mar 2014 19:32|
|RDF:||RDF+N-Triples, RDF+N3, RDF+XML, Browse.|
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