AID induces intraclonal diversity and genomic damage in CD86(+) chronic lymphocytic leukemia cells.
Eur J Immunol
; 44(12): 3747-57, 2014 Dec.
Article
en En
| MEDLINE
| ID: mdl-25179679
ABSTRACT
The activation-induced cytidine deaminase (AID) mediates somatic hypermutation and class switch recombination of the Ig genes by directly deaminating cytosines to uracils. As AID causes a substantial amount of off-target mutations, its activity has been associated with lymphomagenesis and clonal evolution of B-cell malignancies. Although it has been shown that AID is expressed in B-cell chronic lymphocytic leukemia (CLL), a clear analysis of in vivo AID activity in this B-cell malignancy remained elusive. In this study performed on primary human CLL samples, we report that, despite the presence of a dominant VDJ heavy chain region, a substantial intraclonal diversity was observed at VDJ as well as at IgM switch regions (Sµ), showing ongoing AID activity in vivo during disease progression. This AID-mediated heterogeneity was higher in CLL subclones expressing CD86, which we identified as the proliferative CLL fraction. Finally, CD86 expression correlated with shortened time to first treatment and increased γ-H2AX focus formation. Our data demonstrate that AID is active in CLL in vivo and thus, AID likely contributes to clonal evolution of CLL.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Daño del ADN
/
Leucemia Linfocítica Crónica de Células B
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Citidina Desaminasa
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Proliferación Celular
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Antígeno B7-2
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Proteínas de Neoplasias
Límite:
Female
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Humans
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Male
Idioma:
En
Revista:
Eur J Immunol
Año:
2014
Tipo del documento:
Article
País de afiliación:
Austria