An entity evolving into a community: defining the common ancestor and evolutionary trajectory of chronic lymphocytic leukemia stereotyped subset #4

Sutton, Lesley-AnnUppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab (author)

De två första författarna delar förstaförfattarskapet.
Patients 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 in order 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 8 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 dataset 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.

Papadopoulos, Giorgos (author)
Hadzidimitriou, AnastasiaUppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab (author)
Papadopoulos, Stavros (author)
Kostareli, Efterpi (author)
Rosenquist, RichardUppsala universitet,Science for Life Laboratory, SciLifeLab,Experimentell och klinisk onkologi(Swepub:uu)richrose (author)
Tzovaras, Dimitrios (author)
Stamatopoulos, KostasUppsala universitet,Institutionen för immunologi, genetik och patologi(Swepub:uu)kosst292 (author)
Uppsala universitetInstitutionen för immunologi, genetik och patologi (creator_code:org_t)

In:Molecular Medicine: Springer Science and Business Media LLC20:1, s. 720-7281076-15511528-3658

By the author/editor: Sutton, Lesley-A ...; Papadopoulos, Gi ...; Hadzidimitriou, ...; Papadopoulos, St ...; Kostareli, Efter ...; Rosenquist, Rich ...; show more...; Tzovaras, Dimitr ...; Stamatopoulos, K ...; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Medical Genetics

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