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Analysis of IgV H 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
Author(s) -
Degan Massimo,
Bomben Riccardo,
Bo Michele Dal,
Zucchetto Antonella,
Nanni Paola,
Rupolo Maurizio,
Steffan Agostino,
Attadia Vincenza,
Ballerini Pier Ferruccio,
Damiani Daniela,
Pucillo Carlo,
Poeta Giovanni Del,
Colombatti Alfonso,
Gattei Valter
Publication year - 2004
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2004.04985.x
Subject(s) - somatic hypermutation , selection (genetic algorithm) , somatic cell , biology , gene , antigen , genetics , mutation , b cell , immunology , cancer research , antibody , computer science , artificial intelligence
Summary 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 ζ and 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.