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Title

Combined patterns of IGHV repertoire and cytogenetic/molecular alterations in monoclonal B lymphocytosis versus chronic lymphocytic leukemia

AuthorsHenriques, Ana; Rodríguez-Caballero, Arancha; Nieto, Wendy G.; Criado, Ignacio; González, Marcos ; Paiva, Artur; Almeida, Julia ; Orfao, Alberto
Issue Date2013
PublisherPublic Library of Science
CitationPLoS ONE 8(7): e67751 (2013)
Abstract[Background]:Chronic lymphocytic leukemia (CLL)-like monoclonal B lymphocytosis (MBL) with (MBLhi) or without (MBLlo) absolute B-lymphocytosis precedes most CLL cases,the specific determinants for malignant progression remaining unknown. [Methodology/Principal Findings]:For this purpose, simultaneous iFISH and molecular analysis of well-established cytogenetic alterations of chromosomes 11, 12, 13, 14 and 17 together with the pattern of rearrangement of the IGHV genes were performed in CLL-like cells from MBL and CLL cases. Our results based on 78 CLL-like MBL and 117 CLL clones from 166 subjects living in the same geographical area, show the existence of three major groups of clones with distinct but partially overlapping patterns of IGHV gene usage, IGHV mutational status and cytogenetic alterations. These included a group enriched in MBLlo clones expressing specific IGHV subgroups (e.g. VH3-23) with no or isolated good-prognosis cytogenetic alterations, a second group which mainly consisted of clinical MBLhi and advanced stage CLL with a skewed but different CLL-associated IGHV gene repertoire (e.g. VH1-69), frequently associated with complex karyotypes and poor-prognosis cytogenetic alterations, and a third group of clones with intermediate features, with prevalence of mutated IGHV genes, and higher numbers of del(13q)+ clonal B-cells. [Conclusions/Significance]: These findings suggest that the specific IGHV repertoire and IGHV mutational status of CLL-like B-cell clones may modulate the type of cytogenetic alterations acquired, their rate of acquisition and/or potentially also their clinical consequences. Further long-term follow-up studies investigating the IGHV gene repertoire of MBLlo clones in distinct geographic areas and microenvironments are required to confirm our findings and shed light on the potential role of some antigen-binding BCR specificities contributing to clonal evolution.
DescriptionThis is an open-access article distributed under the terms of the Creative Commons Attribution License.-- et al.
Publisher version (URL)http://dx.doi.org/10.1371/journal.pone.0067751
URIhttp://hdl.handle.net/10261/134366
DOI10.1371/journal.pone.0067751
Identifiersdoi: 10.1371/journal.pone.0067751
issn: 1932-6203
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