Advanced

Chronic lymphocytic leukemia with mutated IGHV4-34 receptors : Shared and distinct immunogenetic features and clinical outcomes

Xochelli, Aliki; Baliakas, Panagiotis; Kavakiotis, Ioannis; Agathangelidis, Andreas; Sutton, Lesley-Ann; Minga, Eva; Ntoufa, Stavroula; Tausch, Eugen; Yan, Xiao-Jie and Shanafelt, Tait, et al. (2017) In Clinical Cancer Research 23(17). p.5292-5301
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 IGHV4-34-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... (More)

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.

(Less)
Please use this url to cite or link to this publication:
author
, et al. (More)
(Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
LEUKEMIA, IGHV4-34 Receptors, Clinical Outcomes
in
Clinical Cancer Research
volume
23
issue
17
pages
10 pages
publisher
American Association for Cancer Research
external identifiers
  • scopus:85029456308
  • pmid:28536306
  • wos:000409037300034
ISSN
1078-0432
DOI
10.1158/1078-0432.CCR-16-3100
language
English
LU publication?
yes
id
5a480c19-15c9-4aa5-968b-64540b9df0a1
date added to LUP
2017-10-10 11:45:51
date last changed
2018-01-16 13:22:30
@article{5a480c19-15c9-4aa5-968b-64540b9df0a1,
  abstract     = {<p>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 &lt; 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.</p>},
  author       = {Xochelli, Aliki and Baliakas, Panagiotis and Kavakiotis, Ioannis and Agathangelidis, Andreas and Sutton, Lesley-Ann and Minga, Eva and Ntoufa, Stavroula and Tausch, Eugen and Yan, Xiao-Jie and Shanafelt, Tait and Plevova, 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 Karan-Djurasevic, 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, Marie-Paule 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 Pospisilova, Sarka 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},
  issn         = {1078-0432},
  keyword      = {LEUKEMIA,IGHV4-34 Receptors,Clinical Outcomes},
  language     = {eng},
  month        = {09},
  number       = {17},
  pages        = {5292--5301},
  publisher    = {American Association for Cancer Research},
  series       = {Clinical Cancer Research},
  title        = {Chronic lymphocytic leukemia with mutated IGHV4-34 receptors : Shared and distinct immunogenetic features and clinical outcomes},
  url          = {http://dx.doi.org/10.1158/1078-0432.CCR-16-3100},
  volume       = {23},
  year         = {2017},
}