Publication details

Activation-induced deaminase and its splice variants associate with trisomy 12 in chronic lymphocytic leukemia

Authors

ZÁPRAŽNÁ Kristína RÉBLOVÁ Kamila SVOBODOVA V. RADOVÁ Lenka BYSTRÝ Vojtěch BALOUN Jiří ĎURECHOVÁ Kristina TOM Nikola LOJA Tomáš BUREŠOVÁ Martina STRÁNSKÁ Kamila OLTOVÁ Alexandra DOUBEK Michael ATCHISON M.L. TRBUŠEK Martin MALČÍKOVÁ Jitka POSPÍŠILOVÁ Šárka

Type Article in Periodical
Magazine / Source Annals of hematology
MU Faculty or unit

Central European Institute of Technology

Citation
WWW https://link.springer.com/article/10.1007%2Fs00277-018-3520-5
Doi http://dx.doi.org/10.1007/s00277-018-3520-5
Keywords Activation induced deaminase; Chronic lymphocytic leukemia; Complex karyotype; Alternative splicing; Trisomy 12
Description Activation-induced cytidine deaminase (AID) is a mutator enzyme essential for somatic hypermutation (SHM) and class switch recombination (CSR) during effective adaptive immune responses. Its aberrant expression and activity have been detected in lymphomas, leukemias, and solid tumors. In chronic lymphocytic leukemia (CLL) increased expression of alternatively spliced AID variants has been documented. We used real-time RT-PCR to quantify the expression of AID and its alternatively spliced transcripts (AIDE4a, AIDE4, AIDivs3, and AIDE3E4) in 149 CLL patients and correlated this expression to prognostic markers including recurrent chromosomal aberrations, the presence of complex karyotype, mutation status of the immunoglobulin heavy chain variable gene, and recurrent mutations. We report a previously unappreciated association between higher AID transcript levels and trisomy of chromosome 12. Functional analysis of AID splice variants revealed loss of their activity with respect to SHM, CSR, and induction of double-strand DNA breaks. In silico modeling provided insight into the molecular interactions and structural dynamics of wild-type AID and a shortened AID variant closely resembling AIDE4, confirming its loss-of-function phenotype.
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