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@article{1217014,
author = {Vardi, A. and Agathangelidis, A. and Sutton, L.A. and Chatzouli, M. and Scarfo, L. and Mansouri, L. and Douka, V. and Anagnostopoulos, A. and Darzentas, Nikos and Rosenquist, R. and Ghia, P. and Belessi, C. and Stamatopoulos, K.},
article_location = {PHILADELPHIA},
article_number = {2},
doi = {http://dx.doi.org/10.1158/1078-0432.CCR-13-1993},
keywords = {CHRONIC LYMPHOCYTIC-LEUKEMIA; B-CELL RECEPTOR; GENE MUTATIONAL STATUS; SOMATIC HYPERMUTATION; CLONAL EVOLUTION; UNMUTATED CLL; ANTIGEN; RECOMBINATION; ACTIVATION; EXPRESSION},
language = {eng},
issn = {1078-0432},
journal = {Clinical Cancer Research},
title = {IgG-Switched CLL Has a Distinct Immunogenetic Signature from the Common MD Variant: Ontogenetic Implications},
url = {http://clincancerres.aacrjournals.org/content/20/2/323.long},
volume = {20},
year = {2014}
}
TY - JOUR
ID - 1217014
AU - Vardi, A. - Agathangelidis, A. - Sutton, L.A. - Chatzouli, M. - Scarfo, L. - Mansouri, L. - Douka, V. - Anagnostopoulos, A. - Darzentas, Nikos - Rosenquist, R. - Ghia, P. - Belessi, C. - Stamatopoulos, K.
PY - 2014
TI - IgG-Switched CLL Has a Distinct Immunogenetic Signature from the Common MD Variant: Ontogenetic Implications
JF - Clinical Cancer Research
VL - 20
IS - 2
SP - 323-330
EP - 323-330
PB - American Association for Cancer Research
SN - 10780432
KW - CHRONIC LYMPHOCYTIC-LEUKEMIA
KW - B-CELL RECEPTOR
KW - GENE MUTATIONAL STATUS
KW - SOMATIC HYPERMUTATION
KW - CLONAL EVOLUTION
KW - UNMUTATED CLL
KW - ANTIGEN
KW - RECOMBINATION
KW - ACTIVATION
KW - EXPRESSION
UR - http://clincancerres.aacrjournals.org/content/20/2/323.long
L2 - http://clincancerres.aacrjournals.org/content/20/2/323.long
N2 - Purpose: Immunoglobulin G-switched chronic lymphocytic leukemia (G-CLL) is a rare variant of CLL, whose origin and ontogenetic relationship to the common IgM/IgD (MD-CLL) variant remains undefined. Here, we sought for clues about the ontogeny of G-CLL versus MD-CLL by profiling the relevant IG gene repertoires. Experimental Design: Using purpose-built bioinformatics methods, we performed detailed immunogenetic profiling of a multinational CLL cohort comprising 1,256 cases, of which 1,087 and 169 expressed IG mu/delta and gamma heavy chains, respectively. Results: G-CLL has a highly skewed IG gene repertoire that is distinct from MD-CLL, especially in terms of (i) overuse of the IGHV4-34 and IGHV4-39 genes and (ii) differential somatic hypermutation (SHM) load. Repertoire differences were also found when comparing subgroups with similar SHM status and were mainly attributed to the exclusive representation in G-CLL of two major subsets with quasi-identical (stereotyped) B-cell receptors. These subsets, namely #4 (IGHV4-34/IGKV2-30) and 8 (IGHV4-39/IGKV1(D)-39), were found to display sharply contrasting SHM and clinical behavior. Conclusions: G-CLL exhibits an overall distinct immunogenetic signature from MD-CLL, prompting speculations about distinct ontogenetic derivation and/or immune triggering. The reasons underlying the differential regulation of SHM among G-CLL cases remain to be elucidated. (C) 2013 AACR.
ER -
VARDI, A., A. AGATHANGELIDIS, L.A. SUTTON, M. CHATZOULI, L. SCARFO, L. MANSOURI, V. DOUKA, A. ANAGNOSTOPOULOS, Nikos DARZENTAS, R. ROSENQUIST, P. GHIA, C. BELESSI and K. STAMATOPOULOS. IgG-Switched CLL Has a Distinct Immunogenetic Signature from the Common MD Variant: Ontogenetic Implications. \textit{Clinical Cancer Research}. PHILADELPHIA: American Association for Cancer Research, 2014, vol.~20, No~2, p.~323-330. ISSN~1078-0432. Available from: https://dx.doi.org/10.1158/1078-0432.CCR-13-1993.
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