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

J 2017

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

XOCHELLI, Aliki; Panagiotis BALIAKAS; Ioannis KAVAKIOTIS; Andreas AGATHANGELIDIS; Lesley-Ann SUTTON et al.

Základní údaje

Originální název

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

Autoři

XOCHELLI, Aliki; Panagiotis BALIAKAS; Ioannis KAVAKIOTIS; Andreas AGATHANGELIDIS; Lesley-Ann SUTTON; Eva MINGA; Stavroula NTOUFA; Eugen TAUSCH; Xiao-Jie YAN; Tait SHANAFELT; Karla PLEVOVÁ; Myriam BOUDJOGRA; Davide ROSSI; Zadie DAVIS; Alba NAVARRO; Yorick SANDBERG; Fie Juhl VOJDEMAN; Lydia SCARFO; Niki STAVROYIANNI; Andrey SUDARIKOV; Silvio VERONESE; Tatiana TZENOU; Teodora KARAN-DJURASEVIC; Mark CATHERWOOD; Dirk KIENLE; Maria CHATZOULI; Monica FACCO; Jasmin BAHLO; Christiane POTT; Lone Bredo PEDERSEN; Larry MANSOURI; Karin E. SMEDBY; Charles C. CHU; Veronique GIUDICELLI; Marie-Paule LEFRANC; Panagiotis PANAGIOTIDIS; Gunnar JULIUSSON; Achilles ANAGNOSTOPOULOS; Ioannis VLAHAVAS; Darko ANTIC; Livio TRENTIN; Marco MONTILLO; Carsten NIEMANN; Hartmut DOHNER; Anton W. LANGERAK; Šárka POSPÍŠILOVÁ; Michael HALLEK; Elias CAMPO; Nicholas CHIORAZZI; Nikos MAGLAVERAS; David OSCIER; Gianluca GAIDANO; Diane F. JELINEK; Stephan STILGENBAUER; Ioanna CHOUVARDA; Nikos DARZENTAS; Chrysoula BELESSI; Frederic DAVI; Anastasia HADZIDIMITRIOU; Richard ROSENQUIST; Paolo GHIA a Kostas STAMATOPOULOS

Vydání

Clinical cancer research, Philadelphia, AMER ASSOC CANCER RESEARCH, 2017, 1078-0432

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30200 3.2 Clinical medicine

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 10.199

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14740/17:00098220

Organizační jednotka

Středoevropský technologický institut

Klíčová slova anglicky

B-CELL RECEPTORS; GENE MUTATIONAL STATUS; ANTIGEN RECEPTORS; CD38 EXPRESSION; GENOMIC ABERRATIONS; SEQUENCE-ANALYSIS; I-ANTIGEN; IMMUNOGLOBULIN; ANTIBODIES; DNA

Štítky

MEDGENET, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 1. 3. 2018 14:54, Mgr. Pavla Foltynová, Ph.D.

Anotace

V originále

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.

Návaznosti

LQ1601, projekt VaV

Název: CEITEC 2020 (Akronym: CEITEC2020)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, CEITEC 2020

Citovat

@article{1395067,
   author = {Xochelli, Aliki and Baliakas, Panagiotis and Kavakiotis, Ioannis and Agathangelidis, Andreas and Sutton, LesleyandAnn and Minga, Eva and Ntoufa, Stavroula and Tausch, Eugen and Yan, XiaoandJie and Shanafelt, Tait and Plevová, Karla and Boudjogra, Myriam and Rossi, Davide and Davis, Zadie and Navarro, Alba and Sandberg, Yorick and Vojdeman, Fie Juhl and Scarfo, Lydia and Stavroyianni, Niki and Sudarikov, Andrey and Veronese, Silvio and Tzenou, Tatiana and KaranandDjurasevic, Teodora and Catherwood, Mark and Kienle, Dirk and Chatzouli, Maria and Facco, Monica and Bahlo, Jasmin and Pott, Christiane and Pedersen, Lone Bredo and Mansouri, Larry and Smedby, Karin E. and Chu, Charles C. and Giudicelli, Veronique and Lefranc, MarieandPaule and Panagiotidis, Panagiotis and Juliusson, Gunnar and Anagnostopoulos, Achilles and Vlahavas, Ioannis and Antic, Darko and Trentin, Livio and Montillo, Marco and Niemann, Carsten and Dohner, Hartmut and Langerak, Anton W. and Pospíšilová, Šárka and Hallek, Michael and Campo, Elias and Chiorazzi, Nicholas and Maglaveras, Nikos and Oscier, David and Gaidano, Gianluca and Jelinek, Diane F. and Stilgenbauer, Stephan and Chouvarda, Ioanna and Darzentas, Nikos and Belessi, Chrysoula and Davi, Frederic and Hadzidimitriou, Anastasia and Rosenquist, Richard and Ghia, Paolo and Stamatopoulos, Kostas},
   article_location = {Philadelphia},
   article_number = {17},
   doi = {https://doi.org/10.1158/1078-0432.CCR-16-3100},
   keywords = {B-CELL RECEPTORS; GENE MUTATIONAL STATUS; ANTIGEN RECEPTORS; CD38 EXPRESSION; GENOMIC ABERRATIONS; SEQUENCE-ANALYSIS; I-ANTIGEN; IMMUNOGLOBULIN; ANTIBODIES; DNA},
   language = {eng},
   issn = {1078-0432},
   journal = {Clinical cancer research},
   title = {Chronic Lymphocytic Leukemia with Mutated IGHV4-34 Receptors: Shared and Distinct Immunogenetic Features and Clinical Outcomes},
   url = {http://clincancerres.aacrjournals.org/content/23/17/5292},
   volume = {23},
   year = {2017}
}

TY  - JOUR
ID  - 1395067
AU  - 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
PY  - 2017
TI  - Chronic Lymphocytic Leukemia with Mutated IGHV4-34 Receptors: Shared and Distinct Immunogenetic Features and Clinical Outcomes
JF  - Clinical cancer research
VL  - 23
IS  - 17
SP  - 5292-5301
EP  - 5292-5301
PB  - AMER ASSOC CANCER RESEARCH
SN  - 10780432
KW  - B-CELL RECEPTORS
KW  - GENE MUTATIONAL STATUS
KW  - ANTIGEN RECEPTORS
KW  - CD38 EXPRESSION
KW  - GENOMIC ABERRATIONS
KW  - SEQUENCE-ANALYSIS
KW  - I-ANTIGEN
KW  - IMMUNOGLOBULIN
KW  - ANTIBODIES
KW  - DNA
UR  - http://clincancerres.aacrjournals.org/content/23/17/5292
L2  - http://clincancerres.aacrjournals.org/content/23/17/5292
N2  - 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.
ER  -

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