TY - JOUR
T1 - 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
AU - Degan, Massimo
AU - Bomben, Riccardo
AU - Dal Bo, Michele
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
AU - Colombatti, Alfonso
AU - Gattei, Valter
PY - 2004/7
Y1 - 2004/7
N2 - 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.
AB - 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.
KW - Antigen selection
KW - Chronic lymphocytic leukaemia
KW - Prognosis
KW - Somatic hypermutation
KW - Translesion DNA polymerases
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U2 - 10.1111/j.1365-2141.2004.04985.x
DO - 10.1111/j.1365-2141.2004.04985.x
M3 - Article
C2 - 15198729
AN - SCOPUS:3042829782
VL - 126
SP - 29
EP - 42
JO - British Journal of Haematology
JF - British Journal of Haematology
SN - 0007-1048
IS - 1
ER -