Analysis of IgVH gene mutations in B cell chronic lymphocytic leukaemia according to antigen-driven selection identifies subgroups with different prognosis and usage of the canonical somatic hypermutation machinery

Massimo Degan, Riccardo Bomben, Michele Dal Bo, Antonella Zucchetto, Paola Nanni, Maurizio Rupolo, Agostino Steffan, Vincenza Attadia, Pier Ferruccio Ballerini, Daniela Damiani, Carlo Pucillo, Giovanni Del Poeta, Alfonso Colombatti, Valter Gattei

Research output: Contribution to journalArticle

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Abstract

Cases of B-cell chronic lymphocytic leukaemia (B-CLL) with mutated (M) IgVH genes have a better prognosis than unmutated (UM) cases. We analysed the IgVH mutational status of B-CLL according to the features of a canonical somatic hypermutation (SHM) process, correlating this data with survival. In a series of 141 B-CLLs, 124 cases were examined for IgVH gene per cent mutations and skewing of replacement/silent mutations in the framework/ complementarity-determining regions as evidence of antigen-driven selection; this identified three B-CLL subsets: significantly mutated (sM), with evidence of antigen-driven selection, not significantly mutated (nsM) and UM, without such evidence and IgVH gene per cent mutations above or below the 2% cut-off. sM B-CLL patients had longer survival within the good prognosis subgroup that had more than 2% mutations of IgV H genes. sM, nsM and UM B-CLL were also characterized for the biased usage of IgVH families, intraclonal IgVH gene diversification, preference of mutations to target-specific nucleotides or hotspots, and for the expression of enzymes involved in SHM (translesion DNA polymerase ζ nd η and activation-induced cytidine deaminase). These findings indicate the activation of a canonical SHM process in nsM and sM B-CLLs and underscore the role of the antigen in defining the specific clinical and biological features of B-CLL.

Original languageEnglish
Pages (from-to)29-42
Number of pages14
JournalBritish Journal of Haematology
Volume126
Issue number1
DOIs
Publication statusPublished - Jul 2004

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B-Cell Chronic Lymphocytic Leukemia
Antigens
Mutation
Genes
Complementarity Determining Regions
Survival
DNA-Directed DNA Polymerase
Nucleotides
Enzymes

Keywords

  • Antigen selection
  • Chronic lymphocytic leukaemia
  • Prognosis
  • Somatic hypermutation
  • Translesion DNA polymerases

ASJC Scopus subject areas

  • Hematology

Cite this

Analysis of IgVH gene mutations in B cell chronic lymphocytic leukaemia according to antigen-driven selection identifies subgroups with different prognosis and usage of the canonical somatic hypermutation machinery. / Degan, Massimo; Bomben, Riccardo; Dal Bo, Michele; Zucchetto, Antonella; Nanni, Paola; Rupolo, Maurizio; Steffan, Agostino; Attadia, Vincenza; Ballerini, Pier Ferruccio; Damiani, Daniela; Pucillo, Carlo; Del Poeta, Giovanni; Colombatti, Alfonso; Gattei, Valter.

In: British Journal of Haematology, Vol. 126, No. 1, 07.2004, p. 29-42.

Research output: Contribution to journalArticle

Degan, Massimo ; Bomben, Riccardo ; Dal Bo, Michele ; Zucchetto, Antonella ; Nanni, Paola ; Rupolo, Maurizio ; Steffan, Agostino ; Attadia, Vincenza ; Ballerini, Pier Ferruccio ; Damiani, Daniela ; Pucillo, Carlo ; Del Poeta, Giovanni ; Colombatti, Alfonso ; Gattei, Valter. / Analysis of IgVH gene mutations in B cell chronic lymphocytic leukaemia according to antigen-driven selection identifies subgroups with different prognosis and usage of the canonical somatic hypermutation machinery. In: British Journal of Haematology. 2004 ; Vol. 126, No. 1. pp. 29-42.
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abstract = "Cases of B-cell chronic lymphocytic leukaemia (B-CLL) with mutated (M) IgVH genes have a better prognosis than unmutated (UM) cases. We analysed the IgVH mutational status of B-CLL according to the features of a canonical somatic hypermutation (SHM) process, correlating this data with survival. In a series of 141 B-CLLs, 124 cases were examined for IgVH gene per cent mutations and skewing of replacement/silent mutations in the framework/ complementarity-determining regions as evidence of antigen-driven selection; this identified three B-CLL subsets: significantly mutated (sM), with evidence of antigen-driven selection, not significantly mutated (nsM) and UM, without such evidence and IgVH gene per cent mutations above or below the 2{\%} cut-off. sM B-CLL patients had longer survival within the good prognosis subgroup that had more than 2{\%} mutations of IgV H genes. sM, nsM and UM B-CLL were also characterized for the biased usage of IgVH families, intraclonal IgVH gene diversification, preference of mutations to target-specific nucleotides or hotspots, and for the expression of enzymes involved in SHM (translesion DNA polymerase ζ nd η and activation-induced cytidine deaminase). These findings indicate the activation of a canonical SHM process in nsM and sM B-CLLs and underscore the role of the antigen in defining the specific clinical and biological features of B-CLL.",
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AU - Zucchetto, Antonella

AU - Nanni, Paola

AU - Rupolo, Maurizio

AU - Steffan, Agostino

AU - Attadia, Vincenza

AU - Ballerini, Pier Ferruccio

AU - Damiani, Daniela

AU - Pucillo, Carlo

AU - Del Poeta, Giovanni

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