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dc.contributor.authorSutton, Lesley-Annen
dc.contributor.authorPapadopoulos, Giorgosen
dc.contributor.authorHadzidimitriou, Anastasiaen
dc.contributor.authorPapadopoulos, Stavrosen
dc.contributor.authorKostareli, Efterpien
dc.contributor.authorRosenquist, Richarden
dc.contributor.authorTzovaras, Dimitriosen
dc.contributor.authorStamatopoulos, Kostasen
dc.date.accessioned2017-09-14T15:24:53Z
dc.date.available2017-09-14T15:24:53Z
dc.date.issued2015-04-02
dc.identifier.citationSutton, L.A. et al. (2015) An entity evolving into a community: defining the common ancestor and evolutionary trajectory of chronic lymphocytic leukemia stereotyped subset #4. Molecular Medicine, 20 (1), pp. 720-728en
dc.identifier.urihttp://hdl.handle.net/2086/14487
dc.descriptionWork was completed during previous post-I joined DMU on January 2016en
dc.description.abstractPatients with chronic lymphocytic leukemia (CLL) assigned to stereotyped subset #4 express highly homologous B-cell receptor immunoglobulin (BcR IG) sequences with intense intraclonal diversification (ID) in the context of ongoing somatic hypermutation (SHM). Their remarkable biological and clinical similarities strongly support derivation from a common ancestor. We here revisited ID in subset #4 CLL to reconstruct their evolutionary history as a community of related clones. To this end, using specialized bioinformatics tools we assessed both IGHV-IGHD-IGHJ rearrangements (n = 511) and IGKV-IGKJ rearrangements (n = 397) derived from eight subset #4 cases. Due to high sequence relatedness, a number of subclonal clusters from different cases lay very close to one another, forming a core from which clusters exhibiting greater variation stemmed. Minor subclones from individual cases were mutated to such an extent that they now resembled the sequences of another patient. Viewing the entire subset #4 data set as a single entity branching through diversification enabled inference of a common sequence representing the putative ancestral BcR IG expressed by their still elusive common progenitor. These results have implications for improved understanding of the ontogeny of CLL subset #4, as well as the design of studies concerning the antigenic specificity of the clonotypic BcR IGs.en
dc.language.isoenen
dc.publisherMolecular Medicineen
dc.subjectchronic lymphocytic leukemiaen
dc.subjectimmunogeneticsen
dc.subjectstereotyped subsetsen
dc.titleAn entity evolving into a community: defining the common ancestor and evolutionary trajectory of chronic lymphocytic leukemia stereotyped subset #4.en
dc.typeArticleen
dc.peerreviewedYesen
dc.funderN/Aen
dc.projectidN/Aen
dc.cclicenceCC-BY-NCen
dc.date.acceptance2015-04-02en


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