Chronic Lymphocytic Leukemia with Mutated IGHV4-34 Receptors: Shared and Distinct Immunogenetic Features and Clinical Outcomes
Language English Country United States Media print-electronic
Document type Journal Article
PubMed
28536306
DOI
10.1158/1078-0432.ccr-16-3100
PII: 1078-0432.CCR-16-3100
Knihovny.cz E-resources
- MeSH
- ADP-ribosyl Cyclase 1 genetics immunology MeSH
- Leukemia, Lymphocytic, Chronic, B-Cell genetics immunology pathology MeSH
- Immunogenetics MeSH
- Humans MeSH
- Gene Expression Regulation, Neoplastic immunology MeSH
- Amino Acid Sequence genetics MeSH
- Somatic Hypermutation, Immunoglobulin genetics MeSH
- Immunoglobulin Heavy Chains genetics immunology MeSH
- Immunoglobulin Variable Region genetics immunology MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- ADP-ribosyl Cyclase 1 MeSH
- Immunoglobulin Heavy Chains MeSH
- Immunoglobulin Variable Region MeSH
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 IGHV4-34-expressing 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. Clin Cancer Res; 23(17); 5292-301. ©2017 AACR.
1st Department of Propaedeutic Medicine University of Athens Athens Greece
2nd Medical Department University Hospital Schleswig Holstein Campus Kiel Kiel Germany
Central European Institute of Technology Masaryk University Brno Czech Republic
Clinic for Hematology Clinical Center Belgrade Serbia
Department of Haemato Oncology Belfast City Hospital Belfast United Kingdom
Department of Haematology Royal Bournemouth Hospital Bournemouth United Kingdom
Department of Hematology Department of Medicine Mayo Clinic Rochester Minnesota
Department of Hematology Hopital Pitie Salpetriere and University Pierre et Marie Curie Paris France
Department of Hematology Rigshospitalet Copenhagen Denmark
Department of Immunology Erasmus MC University Medical Center Rotterdam Rotterdam the Netherlands
Department of Immunology Mayo Clinic Rochester Minnesota United States
Department of informatics Aristotle University of Thessaloniki Thessaloniki Greece
Department of Internal Medicine 3 Ulm University Ulm Germany
Department of Medicine Solna Clinical Epidemiology Unit Karolinska Institutet Stockholm Sweden
Department of Molecular Medicine and Surgery Karolinska Institutet Stockholm Sweden
Feinstein Institute for Medical Research Northwell Health Manhasset New York
Hematology Department and HCT Unit G Papanicolaou Hospital Thessaloniki Greece
Hematology Department Nikea General Hospital Piraeus Greece
Institute of Applied Biosciences CERTH Thessaloniki Greece
Institute of Molecular Genetics and Genetic Engineering University of Belgrade Belgrade Serbia
Laboratory of Medical Informatics Aristotle University of Thessaloniki Thessaloniki Greece
Lund University and Hospital Department of Hematology Lund Stem Cell Center Lund Sweden
Medical faculty University of Belgrade Belgrade Serbia
National Research Center for Hematology Moscow Russia
Università Vita Salute San Raffaele and IRCCS Istituto Scientifico San Raffaele Milan Italy
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