Stereotyped B-cell receptors in chronic lymphocytic leukemia

Abstract

Over the last decade, immunogenetic analysis of B-cell receptor immunoglobulins (BcR IGs) has proved to be a particularly fruitful field in chronic lymphocytic leukemia (CLL), not only for understanding disease pathogenesis but also for discriminating clinical subgroups with markedly distinct course and outcome. Of utmost importance was the identification of quasi-identical BcR IGs among unrelated patients with CLL, fittingly coined as “stereotypy,” that set the wheels in motion for unraveling the role of antigen(s) in the selection and expansion of the leukemic clones. The categorization of CLL clones into “subsets” according to shared BcR IG structural characteristics provided a compartmentalized view of this otherwise heterogeneous disease, which eventually led to defining strikingly homogeneous groups of patients in terms of: (i) functional properties of the clonal BcR IGs, e.g. BcR reactivity and signaling; (ii) clonal genetic landscape, e.g. genomic aberrations, gene expression/methylation profiles, microRNA signatures; and (iii) clinical course and outcome. The remarkable restriction of the CLL IG gene repertoire, resulting to a great degree from the high impact of BcR IG stereotypy, may also prompt speculations regarding CLL ontogenesis. Overall, the BcR IG molecule justifiably lies at the heart of CLL clinical research, holding the promise of subset-tailored therapies.

Keywords::

• B-cell receptors
• chronic lymphocytic leukemia
• BcR IG

Acknowledgements

We thank present and past members of our groups for their commitment and enthusiasm.

A special thanks is due to our friends and fellow members of the IgCLL Group (www.igcll.org), Drs. Belessi, Darzentas, Davi, Ghia and Rosenquist, for many years of stimulating and fruitful collaboration.

Finally, we wish to sincerely thank Prof. Marie-Paule Lefranc and Dr. Veronique Giudicelli, Laboratoire d’Immunogenetique Moleculaire, LIGM, Université Montpellier II, Montpellier, France, and IMGT^®, the international ImMunoGeneTics information system^®, http://www.imgt.org, for their enormous support and help with immunoglobulin sequence analysis.

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article at www.informahealthcare.com/lal.

This work was supported in part by the ENosAI project (code 09SYN-13-880) co-funded by the EU and the Hellenic General Secretariat for Research and Technology. K.S. receives research support from Roche SA.