Xochelli, Aliki, Baliakas, Panagiotis, Kavakiotis, Ioannis, Agathangelidis, Andreas, Sutton, Lesley-Ann, Minga, Eva, Ntoufa, Stavroula, Tausch, Eugen, Yan, Xiao-Jie, Shanafelt, Tait, Plevova, Karla ORCID: 0000-0002-6148-8877, Boudjogra, Myriam, Rossi, Davide, Davis, Zadie, Navarro, Alba, Sandberg, Yorick, Vojdeman, Fie Juhl, Scarfo, Lydia, Stavroyianni, Niki, Sudarikov, Andrey ORCID: 0000-0001-9463-9187, Veronese, Silvio, Tzenou, Tatiana, Karan-Djurasevic, Teodora, Catherwood, Mark, Kienle, Dirk, Chatzouli, Maria, Facco, Monica ORCID: 0000-0003-0100-5789, 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 ORCID: 0000-0003-4384-9031, Vlahavas, Ioannis, Antic, Darko, Trentin, Livio, Montillo, Marco, Niemann, Carsten ORCID: 0000-0001-9880-5242, Doehner, Hartmut, Langerak, Anton W., Pospisilova, Sarka, Hallek, Michael, Campo, Elias ORCID: 0000-0001-9850-9793, Chiorazzi, Nicholas, Maglaveras, Nikos, Oscier, David, Gaidano, Gianluca, Jelinek, Diane F., Stilgenbauer, Stephan, Chouvarda, Ioanna ORCID: 0000-0001-8915-6658, Darzentas, Nikos, Belessi, Chrysoula, Davi, Frederic, Hadzidimitriou, Anastasia, Rosenquist, Richard, Ghia, Paolo ORCID: 0000-0003-3750-7342 and Stamatopoulos, Kostas (2017). Chronic Lymphocytic Leukemia with Mutated IGHV4-34 Receptors: Shared and Distinct Immunogenetic Features and Clinical Outcomes. Clin. Cancer Res., 23 (17). S. 5292 - 5302. PHILADELPHIA: AMER ASSOC CANCER RESEARCH. ISSN 1557-3265

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Abstract

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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Xochelli, AlikiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Baliakas, PanagiotisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kavakiotis, IoannisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Agathangelidis, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sutton, Lesley-AnnUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Minga, EvaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ntoufa, StavroulaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tausch, EugenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yan, Xiao-JieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Shanafelt, TaitUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Plevova, KarlaUNSPECIFIEDorcid.org/0000-0002-6148-8877UNSPECIFIED
Boudjogra, MyriamUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rossi, DavideUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Davis, ZadieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Navarro, AlbaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sandberg, YorickUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vojdeman, Fie JuhlUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Scarfo, LydiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stavroyianni, NikiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sudarikov, AndreyUNSPECIFIEDorcid.org/0000-0001-9463-9187UNSPECIFIED
Veronese, SilvioUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tzenou, TatianaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Karan-Djurasevic, TeodoraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Catherwood, MarkUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kienle, DirkUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chatzouli, MariaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Facco, MonicaUNSPECIFIEDorcid.org/0000-0003-0100-5789UNSPECIFIED
Bahlo, JasminUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pott, ChristianeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pedersen, Lone BredoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mansouri, LarryUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Smedby, Karin E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chu, Charles C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Giudicelli, VeroniqueUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lefranc, Marie-PauleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Panagiotidis, PanagiotisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Juliusson, GunnarUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Anagnostopoulos, AchillesUNSPECIFIEDorcid.org/0000-0003-4384-9031UNSPECIFIED
Vlahavas, IoannisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Antic, DarkoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Trentin, LivioUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Montillo, MarcoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Niemann, CarstenUNSPECIFIEDorcid.org/0000-0001-9880-5242UNSPECIFIED
Doehner, HartmutUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Langerak, Anton W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pospisilova, SarkaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hallek, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Campo, EliasUNSPECIFIEDorcid.org/0000-0001-9850-9793UNSPECIFIED
Chiorazzi, NicholasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Maglaveras, NikosUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Oscier, DavidUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gaidano, GianlucaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jelinek, Diane F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stilgenbauer, StephanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chouvarda, IoannaUNSPECIFIEDorcid.org/0000-0001-8915-6658UNSPECIFIED
Darzentas, NikosUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Belessi, ChrysoulaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Davi, FredericUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hadzidimitriou, AnastasiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rosenquist, RichardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ghia, PaoloUNSPECIFIEDorcid.org/0000-0003-3750-7342UNSPECIFIED
Stamatopoulos, KostasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-220630
DOI: 10.1158/1078-0432.CCR-16-3100
Journal or Publication Title: Clin. Cancer Res.
Volume: 23
Number: 17
Page Range: S. 5292 - 5302
Date: 2017
Publisher: AMER ASSOC CANCER RESEARCH
Place of Publication: PHILADELPHIA
ISSN: 1557-3265
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
B-CELL RECEPTOR; GENE MUTATIONAL STATUS; CD38 EXPRESSION; GENOMIC ABERRATIONS; ANTIGEN SELECTION; IMMUNOGLOBULIN; IG; ANTIBODIES; DNA; CLLMultiple languages
OncologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/22063

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