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.
Br J Haematol
; 126(1): 29-42, 2004 Jul.
Article
em En
| MEDLINE
| ID: mdl-15198729
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Região Variável de Imunoglobulina
/
Leucemia Linfocítica Crônica de Células B
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Hipermutação Somática de Imunoglobulina
Tipo de estudo:
Observational_studies
/
Prognostic_studies
Limite:
Adult
/
Aged
/
Aged80
/
Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Br J Haematol
Ano de publicação:
2004
Tipo de documento:
Article
País de afiliação:
Itália