Cases of B-cell chronic lymphocytic leukaemia (B-CLL) with mutated (M) IgV(H) genes have a better prognosis than unmutated (UM) cases. We analysed the IgV(H) 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 IgV(H) 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 IgV(H) 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 IgV(H) families, intraclonal IgV(H) gene diversification, preference of mutations to target-specific nucleotides or hotspots, and for the expression of enzymes involved in SHM (translesion DNA polymerase zeta and eta 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.

Degan, M., Bomben, R., Bo, M., Zucchetto, A., Nanni, P., Rupolo, M., et al. (2004). Analysis of IgV 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. BRITISH JOURNAL OF HAEMATOLOGY, 126(1), 29-42 [10.1111/j.1365-2141.2004.04985.x].

Analysis of IgV 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

DEL POETA, GIOVANNI;
2004

Abstract

Cases of B-cell chronic lymphocytic leukaemia (B-CLL) with mutated (M) IgV(H) genes have a better prognosis than unmutated (UM) cases. We analysed the IgV(H) 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 IgV(H) 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 IgV(H) 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 IgV(H) families, intraclonal IgV(H) gene diversification, preference of mutations to target-specific nucleotides or hotspots, and for the expression of enzymes involved in SHM (translesion DNA polymerase zeta and eta 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.
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore MED/15 - Malattie del Sangue
English
Con Impact Factor ISI
Chi-Square Distribution; DNA Mutational Analysis; Humans; Gene Expression; Aged; Somatic Hypermutation, Immunoglobulin; Survival Rate; Leukemia, Lymphocytic, Chronic, B-Cell; Aged, 80 and over; Adult; Point Mutation; Immunoglobulin Variable Region; Middle Aged; Follow-Up Studies; Immunophenotyping; Male; Female; DNA-Directed DNA Polymerase
Degan, M., Bomben, R., Bo, M., Zucchetto, A., Nanni, P., Rupolo, M., et al. (2004). Analysis of IgV 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. BRITISH JOURNAL OF HAEMATOLOGY, 126(1), 29-42 [10.1111/j.1365-2141.2004.04985.x].
Degan, M; Bomben, R; Bo, M; Zucchetto, A; Nanni, P; Rupolo, M; Steffan, A; Attadia, V; Ballerini, P; Damiani, D; Pucillo, C; DEL POETA, G; Colombatti, A; Gattei, V
Articolo su rivista
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/34935
Citazioni
  • ???jsp.display-item.citation.pmc??? 15
  • Scopus 56
  • ???jsp.display-item.citation.isi??? 52
social impact