uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Temporal dynamics of clonal evolution in chronic lymphocytic leukemia with stereotyped IGHV4-34/IGKV2-30 antigen receptors: longitudinal immunogenetic evidence
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
Show others and affiliations
2013 (English)In: Molecular medicine (Cambridge, Mass. Print), ISSN 1076-1551, E-ISSN 1528-3658, Vol. 19, 230-236 p.Article in journal (Refereed) Published
Abstract [en]

Chronic lymphocytic leukemia (CLL) patients assigned to stereotyped subset 4 possess distinctive patterns of intraclonal diversification (ID) within their immunoglobulin (IG) genes. Although highly indicative of an ongoing response to antigen(s), the critical question concerning the precise timing of antigen involvement is unresolved. Hence, we conducted a large-scale longitudinal study of eight subset 4 cases totaling 511 and 398 subcloned IG heavy and kappa sequences. Importantly, we could establish a hierarchical pattern of subclonal evolution, thus revealing which somatic hypermutations were negatively or positively selected. In addition, distinct clusters of subcloned sequences with cluster-specific mutational profiles were observed initially; however, at later time points, the minor cluster had often disappeared and hence not been selected. Despite the high intensity of ID, it was remarkable that certain residues remained essentially unaltered. These novel findings strongly support a role for persistent antigen stimulation in the clonal evolution of CLL subset 4.

Place, publisher, year, edition, pages
2013. Vol. 19, 230-236 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-214212DOI: 10.2119/molmed.2013.00042ISI: 000328604700008PubMedID: 23922244OAI: oai:DiVA.org:uu-214212DiVA: diva2:684436
Available from: 2014-01-08 Created: 2014-01-08 Last updated: 2014-01-17Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Sutton, Lesley-AnnRosenquist, Richard
By organisation
Department of Immunology, Genetics and Pathology
In the same journal
Molecular medicine (Cambridge, Mass. Print)
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 214 hits
ReferencesLink to record
Permanent link

Direct link