Molecular and clinical features of chronic lymphocytic leukemia with stereotyped B-cell receptors in a Ukrainian cohort

Abstract

A fraction of chronic lymphocytic leukemia (CLL) carries highly homologous B-cell receptors, characterized by non-random combinations of immunoglobulin heavy-chain variable (IGHV) genes and heavy-chain complementarity-determining region-3 (HCDR3), often associated with a restricted selection of IG(K/L)V light chains. We analyzed the features of CLL expressing homologous HCDR3 in a cohort of 264 Ukrainian patients by merging them with a recently published reference series of 1426 cases. This approach allowed us to identify 96/264 (36%) cases as expressing homologous HCDR3, subdivided into 47 subsets. Among these, 27 apparently novel subsets were identified, although most of them were composed of two sequences per subset (‘potential subsets’). CLL cases belonging to several stereotyped subsets showed HCDR3 homologies with various autoreactive clones. Our analysis identified molecular and clinical features of a Ukrainian cohort of patients with CLL.

Keywords:

• Chronic lymphocytic leukemia
• IGHV genes
• stereotyped B-cell receptor

Declaration of interest: This study was supported in part by: Ministero della Salute (Ricerca Finalizzata I.R.C.C.S. and ‘Alleanza Contro il Cancro’), Rome, Italy; Associazione Italiana contro le Leucemie, linfomi e mielomi (A.I.L.), Venezia Section, Pramaggiore Group, Italy; Ricerca Scientifica Applicata, Regione Friuli Venezia Giulia, Trieste (‘Linfonet’), Italy; Programmi di Ricerca di Interesse Nazionale (P.R.I.N.) and Fondo per gli Investimenti per la Ricerca di Base (F.I.R.B.), M.U.R., Rome, Italy; Novara-A.I.L. Onlus, Novara, Italy; Ricerca Sanitaria Finalizzata Regione Piemonte, Torino, Italy; Associazione Italiana per la Ricerca sul Cancro (A.I.R.C.), Milan, Italy; Piano di Ateneo per la Ricerca (P.A.R.) 2005, University of Siena, Italy; Hairy Cell Leukemia Research Foundation (Illinois, USA); Helmut Horten Foundation (Lugano, Switzerland); San Salvatore Foundation (Lugano, Switzerland); Fondazione per la Ricerca e la Cura sui Linfomi (Lugano, Switzerland); KIHEV Kinderhilfe Kiew e.V. (Weil am Rhein, Germany).