Over 30% of patients with splenic marginal zone lymphoma express the same immunoglobulin heavy variable gene: Ontogenetic implications

V. Bikos, N. Darzentas, A. Hadzidimitriou, Z. Davis, S. Hockley, A. Traverse-Glehen, P. Algara, A. Santoro, D. Gonzalez, M. Mollejo, A. Dagklis, F. Gangemi, D. S. Bosler, G. Bourikas, A. Anagnostopoulos, A. Tsaftaris, E. Iannitto, M. Ponzoni, P. Felman, F. BergerC. Belessi, P. Ghia, T. Papadaki, A. Dogan, M. Degano, E. Matutes, M. A. Piris, D. Oscier, K. Stamatopoulos

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

We performed an immunogenetic analysis of 345 IGHV-IGHD-IGHJ rearrangements from 337 cases with primary splenic small B-cell lymphomas of marginal-zone origin. Three immunoglobulin (IG) heavy variable (IGHV) genes accounted for 45.8% of the cases (IGHV1-2, 24.9%; IGHV4-34, 12.8%; IGHV3-23, 8.1%). Particularly for the IGHV1-2 gene, strong biases were evident regarding utilization of different alleles, with 79/86 rearrangements (92%) using allele 04. Among cases more stringently classified as splenic marginal-zone lymphoma (SMZL) thanks to the availability of splenic histopathological specimens, the frequency of IGHV1-2 04 peaked at 31%. The IGHV1-2 04 rearrangements carried significantly longer complementarity-determining region-3 (CDR3) than all other cases and showed biased IGHD gene usage, leading to CDR3s with common motifs. The great majority of analyzed rearrangements (299/345, 86.7%) carried IGHV genes with some impact of somatic hypermutation, from minimal to pronounced. Noticeably, 75/79 (95%) IGHV1-2 04 rearrangements were mutated; however, they mostly (56/75 cases; 74.6%) carried few mutations (97-99.9% germline identity) of conservative nature and restricted distribution. These distinctive features of the IG receptors indicate selection by (super)antigenic element(s) in the pathogenesis of SMZL. Furthermore, they raise the possibility that certain SMZL subtypes could derive from progenitor populations adapted to particular antigenic challenges through selection of VH domain specificities, in particular the IGHV1-2 04 allele.

Original languageEnglish (US)
Pages (from-to)1638-1646
Number of pages9
JournalLeukemia
Volume26
Issue number7
DOIs
StatePublished - Jul 2012

Fingerprint

Immunoglobulins
Lymphoma
Alleles
Genes
Complementarity Determining Regions
Immunogenetics
B-Cell Lymphoma
B-Cell Chronic Lymphocytic Leukemia
Mutation
Population

Keywords

  • antigen
  • CDR3
  • immunoglobulin gene
  • somatic hypermutation
  • splenic marginal-zone lymphoma

ASJC Scopus subject areas

  • Hematology
  • Cancer Research
  • Anesthesiology and Pain Medicine

Cite this

Bikos, V., Darzentas, N., Hadzidimitriou, A., Davis, Z., Hockley, S., Traverse-Glehen, A., ... Stamatopoulos, K. (2012). Over 30% of patients with splenic marginal zone lymphoma express the same immunoglobulin heavy variable gene: Ontogenetic implications. Leukemia, 26(7), 1638-1646. https://doi.org/10.1038/leu.2012.3

Over 30% of patients with splenic marginal zone lymphoma express the same immunoglobulin heavy variable gene : Ontogenetic implications. / Bikos, V.; Darzentas, N.; Hadzidimitriou, A.; Davis, Z.; Hockley, S.; Traverse-Glehen, A.; Algara, P.; Santoro, A.; Gonzalez, D.; Mollejo, M.; Dagklis, A.; Gangemi, F.; Bosler, D. S.; Bourikas, G.; Anagnostopoulos, A.; Tsaftaris, A.; Iannitto, E.; Ponzoni, M.; Felman, P.; Berger, F.; Belessi, C.; Ghia, P.; Papadaki, T.; Dogan, A.; Degano, M.; Matutes, E.; Piris, M. A.; Oscier, D.; Stamatopoulos, K.

In: Leukemia, Vol. 26, No. 7, 07.2012, p. 1638-1646.

Research output: Contribution to journalArticle

Bikos, V, Darzentas, N, Hadzidimitriou, A, Davis, Z, Hockley, S, Traverse-Glehen, A, Algara, P, Santoro, A, Gonzalez, D, Mollejo, M, Dagklis, A, Gangemi, F, Bosler, DS, Bourikas, G, Anagnostopoulos, A, Tsaftaris, A, Iannitto, E, Ponzoni, M, Felman, P, Berger, F, Belessi, C, Ghia, P, Papadaki, T, Dogan, A, Degano, M, Matutes, E, Piris, MA, Oscier, D & Stamatopoulos, K 2012, 'Over 30% of patients with splenic marginal zone lymphoma express the same immunoglobulin heavy variable gene: Ontogenetic implications', Leukemia, vol. 26, no. 7, pp. 1638-1646. https://doi.org/10.1038/leu.2012.3
Bikos, V. ; Darzentas, N. ; Hadzidimitriou, A. ; Davis, Z. ; Hockley, S. ; Traverse-Glehen, A. ; Algara, P. ; Santoro, A. ; Gonzalez, D. ; Mollejo, M. ; Dagklis, A. ; Gangemi, F. ; Bosler, D. S. ; Bourikas, G. ; Anagnostopoulos, A. ; Tsaftaris, A. ; Iannitto, E. ; Ponzoni, M. ; Felman, P. ; Berger, F. ; Belessi, C. ; Ghia, P. ; Papadaki, T. ; Dogan, A. ; Degano, M. ; Matutes, E. ; Piris, M. A. ; Oscier, D. ; Stamatopoulos, K. / Over 30% of patients with splenic marginal zone lymphoma express the same immunoglobulin heavy variable gene : Ontogenetic implications. In: Leukemia. 2012 ; Vol. 26, No. 7. pp. 1638-1646.
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abstract = "We performed an immunogenetic analysis of 345 IGHV-IGHD-IGHJ rearrangements from 337 cases with primary splenic small B-cell lymphomas of marginal-zone origin. Three immunoglobulin (IG) heavy variable (IGHV) genes accounted for 45.8{\%} of the cases (IGHV1-2, 24.9{\%}; IGHV4-34, 12.8{\%}; IGHV3-23, 8.1{\%}). Particularly for the IGHV1-2 gene, strong biases were evident regarding utilization of different alleles, with 79/86 rearrangements (92{\%}) using allele 04. Among cases more stringently classified as splenic marginal-zone lymphoma (SMZL) thanks to the availability of splenic histopathological specimens, the frequency of IGHV1-2 04 peaked at 31{\%}. The IGHV1-2 04 rearrangements carried significantly longer complementarity-determining region-3 (CDR3) than all other cases and showed biased IGHD gene usage, leading to CDR3s with common motifs. The great majority of analyzed rearrangements (299/345, 86.7{\%}) carried IGHV genes with some impact of somatic hypermutation, from minimal to pronounced. Noticeably, 75/79 (95{\%}) IGHV1-2 04 rearrangements were mutated; however, they mostly (56/75 cases; 74.6{\%}) carried few mutations (97-99.9{\%} germline identity) of conservative nature and restricted distribution. These distinctive features of the IG receptors indicate selection by (super)antigenic element(s) in the pathogenesis of SMZL. Furthermore, they raise the possibility that certain SMZL subtypes could derive from progenitor populations adapted to particular antigenic challenges through selection of VH domain specificities, in particular the IGHV1-2 04 allele.",
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AU - Bikos, V.

AU - Darzentas, N.

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AU - Davis, Z.

AU - Hockley, S.

AU - Traverse-Glehen, A.

AU - Algara, P.

AU - Santoro, A.

AU - Gonzalez, D.

AU - Mollejo, M.

AU - Dagklis, A.

AU - Gangemi, F.

AU - Bosler, D. S.

AU - Bourikas, G.

AU - Anagnostopoulos, A.

AU - Tsaftaris, A.

AU - Iannitto, E.

AU - Ponzoni, M.

AU - Felman, P.

AU - Berger, F.

AU - Belessi, C.

AU - Ghia, P.

AU - Papadaki, T.

AU - Dogan, A.

AU - Degano, M.

AU - Matutes, E.

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AU - Oscier, D.

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