Publication details

Chronic Lymphocytic Leukemia with Mutated IGHV4-34 Receptors: Shared and Distinct Immunogenetic Features and Clinical Outcomes

Authors	XOCHELLI Aliki BALIAKAS Panagiotis KAVAKIOTIS Ioannis AGATHANGELIDIS Andreas SUTTON Lesley-Ann MINGA Eva NTOUFA Stavroula TAUSCH Eugen YAN Xiao-Jie SHANAFELT Tait PLEVOVÁ Karla BOUDJOGRA Myriam ROSSI Davide DAVIS Zadie NAVARRO Alba SANDBERG Yorick VOJDEMAN Fie Juhl SCARFO Lydia STAVROYIANNI Niki SUDARIKOV Andrey VERONESE Silvio TZENOU Tatiana KARAN-DJURASEVIC Teodora CATHERWOOD Mark KIENLE Dirk CHATZOULI Maria FACCO Monica BAHLO Jasmin POTT Christiane PEDERSEN Lone Bredo MANSOURI Larry SMEDBY Karin E. CHU Charles C. GIUDICELLI Veronique LEFRANC Marie-Paule PANAGIOTIDIS Panagiotis JULIUSSON Gunnar ANAGNOSTOPOULOS Achilles VLAHAVAS Ioannis ANTIC Darko TRENTIN Livio MONTILLO Marco NIEMANN Carsten DOHNER Hartmut LANGERAK Anton W. POSPÍŠILOVÁ Šárka HALLEK Michael CAMPO Elias CHIORAZZI Nicholas MAGLAVERAS Nikos OSCIER David GAIDANO Gianluca JELINEK Diane F. STILGENBAUER Stephan CHOUVARDA Ioanna DARZENTAS Nikos BELESSI Chrysoula DAVI Frederic HADZIDIMITRIOU Anastasia ROSENQUIST Richard GHIA Paolo STAMATOPOULOS Kostas
Year of publication	2017
Type	Article in Periodical
Magazine / Source	Clinical cancer research
MU Faculty or unit	Central European Institute of Technology
Citation
Web	http://clincancerres.aacrjournals.org/content/23/17/5292
Doi	http://dx.doi.org/10.1158/1078-0432.CCR-16-3100
Field	Oncology and hematology
Keywords	B-CELL RECEPTORS; GENE MUTATIONAL STATUS; ANTIGEN RECEPTORS; CD38 EXPRESSION; GENOMIC ABERRATIONS; SEQUENCE-ANALYSIS; I-ANTIGEN; IMMUNOGLOBULIN; ANTIBODIES; DNA
Description	Purpose: We sought to investigate whether B cell receptor immunoglobulin (BcR IG) stereotypy is associated with particular clinicobiological features among chronic lymphocytic leukemia (CLL) patients expressing mutated BcR IG (M-CLL) encoded by the IGHV4-34 gene, and also ascertain whether these associations could refine prognostication. Experimental Design: In a series of 19,907 CLL cases with available immunogenetic information, we identified 339 IGHV4-34expressing cases assigned to one of the four largest stereotyped M-CLL subsets, namely subsets #4, #16, #29 and #201, and investigated in detail their clinicobiological characteristics and disease outcomes. Results: We identified shared and subset-specific patterns of somatic hypermutation (SHM) among patients assigned to these subsets. The greatest similarity was observed between subsets #4 and #16, both including IgG-switched cases (IgG-CLL). In contrast, the least similarity was detected between subsets #16 and #201, the latter concerning IgM/D-expressing CLL. Significant differences between subsets also involved disease stage at diagnosis and the presence of specific genomic aberrations. IgG subsets #4 and #16 emerged as particularly indolent with a significantly (P < 0.05) longer time-to-first-treatment (TTFT; median TTFT: not yet reached) compared with the IgM/D subsets #29 and #201 (median TTFT: 11 and 12 years, respectively). Conclusions: Our findings support the notion that BcR IG stereotypy further refines prognostication in CLL, superseding the immunogenetic distinction based solely on SHM load. In addition, the observed distinct genetic aberration landscapes and clinical heterogeneity suggest that not all M-CLL cases are equal, prompting further research into the underlying biological background with the ultimate aim of tailored patient management. (C) 2017 AACR.
Related projects:	CEITEC 2020