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IgG-Switched CLL Has a Distinct Immunogenetic Signature from the Common MD Variant: Ontogenetic Implications
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
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2014 (English)In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 20, no 2, 323-330 p.Article in journal (Refereed) Published
Abstract [en]


IgG-switched chronic lymphocytic leukemia (G-CLL) is a rare variant of CLL, whose origin and ontogenetic relationship to the common IgM/IgD (MD-CLL) variant remains undefined. Here we sought for clues regarding the ontogeny of G-CLL versus MD-CLL by profiling the relevant IG gene repertoires.


Using purpose-built bioinformatics methods, we performed detailed immunogenetic profiling of a multinational CLL cohort comprising 1256 cases, of which 1087 and 169 expressed IG mu/delta and gamma heavy chains, respectively.


G-CLL has a highly skewed IG gene repertoire that is distinct from MD-CLL, especially in terms of: (i) overuse of the IGHV4-34 and IGHV4-39 genes; and, (ii) differential somatic hypermutation (SHM) load. Repertoire differences held also when comparing subgroups with similar SHM status and were mainly attributed to the exclusive representation in G-CLL of two major subsets with quasi-identical (stereotyped) B-cell receptors. These subsets, namely #4 (IGHV4-34/IGKV2-30) and #8 (IGHV4-39/IGKV1(D)-39), were found to display sharply contrasting SHM and clinical behavior.


G-CLL exhibits an overall distinct immunogenetic signature from MD-CLL, prompting speculations about distinct ontogenetic derivation and/or immune triggering. The reasons underlying the differential regulation of SHM among G-CLL cases remain to be elucidated.

Place, publisher, year, edition, pages
2014. Vol. 20, no 2, 323-330 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-214251DOI: 10.1158/1078-0432.CCR-13-1993ISI: 000329918600008PubMedID: 24240110OAI: oai:DiVA.org:uu-214251DiVA: diva2:684516
Available from: 2014-01-08 Created: 2014-01-08 Last updated: 2014-02-20Bibliographically approved

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Sutton, Lesley-AnnMansouri, LarryRosenquist, Richard
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