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An Immunogenetic Signature of Ongoing Antigen Interactions in Splenic Marginal Zone Lymphoma Expressing IGHV1-2*04 Receptors
V. Bikos, M. Karypidou, E. Stalika, P. Baliakas, A. Xochelli, LA. Sutton, G. Papadopoulos, A. Agathangelidis, E. Papadopoulou, Z. Davis, P. Algara, G. Kanellis, A. Traverse-Glehen, M. Mollejo, A. Anagnostopoulos, M. Ponzoni, D. Gonzalez, S....
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články, práce podpořená grantem
NLK
Free Medical Journals
od 1995 do Před 1 rokem
Freely Accessible Science Journals
od 1995
Open Access Digital Library
od 1995-01-01
Open Access Digital Library
od 1995-01-01
- MeSH
- alely * MeSH
- aminokyselinové motivy MeSH
- antigeny imunologie MeSH
- biologické modely MeSH
- hypervariabilní oblasti chemie genetika MeSH
- lidé MeSH
- lymfom z B-buněk marginální zóny genetika imunologie patologie MeSH
- mutace MeSH
- nádory sleziny genetika imunologie patologie MeSH
- přestavba genů pro těžké řetězce B-lymfocytů MeSH
- receptory antigenů B-buněk genetika MeSH
- sekvence aminokyselin MeSH
- stanovení celkové genové exprese MeSH
- substituce aminokyselin MeSH
- těžké řetězce imunoglobulinů chemie genetika MeSH
- transkriptom MeSH
- variabilní oblast imunoglobulinu chemie genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
PURPOSE: Prompted by the extensive biases in the immunoglobulin (IG) gene repertoire of splenic marginal-zone lymphoma (SMZL), supporting antigen selection in SMZL ontogeny, we sought to investigate whether antigen involvement is also relevant post-transformation. EXPERIMENTAL DESIGN: We conducted a large-scale subcloning study of the IG rearrangements of 40 SMZL cases aimed at assessing intraclonal diversification (ID) due to ongoing somatic hypermutation (SHM). RESULTS: ID was identified in 17 of 21 (81%) rearrangements using the immunoglobulin heavy variable (IGHV)1-2*04 gene versus 8 of 19 (40%) rearrangements utilizing other IGHV genes (P= 0.001). ID was also evident in most analyzed IG light chain gene rearrangements, albeit was more limited compared with IG heavy chains. Identical sequence changes were shared by subclones from different patients utilizing the IGHV1-2*04 gene, confirming restricted ongoing SHM profiles. Non-IGHV1-2*04 cases displayed both a lower number of ongoing SHMs and a lack of shared mutations (per group of cases utilizing the same IGHV gene). CONCLUSIONS: These findings support ongoing antigen involvement in a sizable portion of SMZL and further argue that IGHV1-2*04 SMZL may represent a distinct molecular subtype of the disease.
Central European Institute of Technology Masaryk University Brno Czech Republic
Department of Haematology Royal Bournemouth Hospital Bournemouth United Kingdom
Department of Pathology and Hematology Hospices Civils de Lyon Universite Lyon Lyon France
Department of Pathology Hospital Virgen de la Salud Toledo Spain
Hematology Department and HCT Unit G Papanicolaou Hospital Thessaloniki Greece
Hematology Department Nikea General Hospital Pireaus Greece
Hematopathology Department Evangelismos Hospital Athens Greece
Hospital Universitario Marques de Valdecilla Santander Cantabria Spain
Information Technologies Institute CERTH Thessaloniki Greece
Institute of Applied Biosciences CERTH Thessaloniki Greece
Pathology Unit San Raffaele Scientific Institute Milan Italy
Section of Haemato Oncology Institute of Cancer Research London United Kingdom
Citace poskytuje Crossref.org
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- $a Bikos, Vasilis $u Hematology Department and HCT Unit, G. Papanicolaou Hospital, Thessaloniki, Greece. Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
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- $a PURPOSE: Prompted by the extensive biases in the immunoglobulin (IG) gene repertoire of splenic marginal-zone lymphoma (SMZL), supporting antigen selection in SMZL ontogeny, we sought to investigate whether antigen involvement is also relevant post-transformation. EXPERIMENTAL DESIGN: We conducted a large-scale subcloning study of the IG rearrangements of 40 SMZL cases aimed at assessing intraclonal diversification (ID) due to ongoing somatic hypermutation (SHM). RESULTS: ID was identified in 17 of 21 (81%) rearrangements using the immunoglobulin heavy variable (IGHV)1-2*04 gene versus 8 of 19 (40%) rearrangements utilizing other IGHV genes (P= 0.001). ID was also evident in most analyzed IG light chain gene rearrangements, albeit was more limited compared with IG heavy chains. Identical sequence changes were shared by subclones from different patients utilizing the IGHV1-2*04 gene, confirming restricted ongoing SHM profiles. Non-IGHV1-2*04 cases displayed both a lower number of ongoing SHMs and a lack of shared mutations (per group of cases utilizing the same IGHV gene). CONCLUSIONS: These findings support ongoing antigen involvement in a sizable portion of SMZL and further argue that IGHV1-2*04 SMZL may represent a distinct molecular subtype of the disease.
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