Related Experiment Video
Updated: May 5, 2026
Immunoglobulin Gene Sequence Analysis In Chronic Lymphocytic Leukemia: From Patient Material To Sequence Interpretation
Published on: November 26, 2018
IgG-switched CLL has a distinct immunogenetic signature from the common MD variant: ontogenetic implications
Anna Vardi1, Andreas Agathangelidis, Lesley-Ann Sutton
1Authors' Affiliations: Hematology Department and HCT Unit, G. Papanicolaou Hospital; Institute of Applied Biosciences, Centre for Research & Technology Hellas, Thessaloniki, Greece; Division of Molecular Oncology, San Raffaele Scientific Institute, Milan, Italy; Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden; Hematology Department, Nikea General Hospital, Piraeus, Greece; and Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
Purpose:
Immunoglobulin G-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 about the ontogeny of G-CLL versus MD-CLL by profiling the relevant IG gene repertoires.
Experimental Design:
Using purpose-built bioinformatics methods, we performed detailed immunogenetic profiling of a multinational CLL cohort comprising 1,256 cases, of which 1,087 and 169 expressed IG mu/delta and gamma heavy chains, respectively.
Results:
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 were also found 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.
Conclusions:
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.
