IgG-switched CLL has a distinct immunogenetic signature from the common MD variant: ontogenetic implications
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
24240110
DOI
10.1158/1078-0432.ccr-13-1993
PII: 1078-0432.CCR-13-1993
Knihovny.cz E-zdroje
- MeSH
- chronická lymfatická leukemie genetika imunologie MeSH
- dospělí MeSH
- genová přestavba B-lymfocytů MeSH
- imunogenetika MeSH
- imunoglobulin D genetika MeSH
- imunoglobulin G genetika MeSH
- imunoglobulin M genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- receptory antigenů B-buněk klasifikace genetika MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- somatická hypermutace imunoglobulinových genů MeSH
- těžké řetězce imunoglobulinů genetika MeSH
- variabilní oblast imunoglobulinu genetika MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- imunoglobulin D MeSH
- imunoglobulin G MeSH
- imunoglobulin M MeSH
- receptory antigenů B-buněk MeSH
- těžké řetězce imunoglobulinů MeSH
- variabilní oblast imunoglobulinu MeSH
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.
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