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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F65269705%3A_____%2F19%3A00070526" target="_blank" >RIV/65269705:_____/19:00070526 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216224:14740/19:00109169

Výsledek na webu

<a href="https://link.springer.com/article/10.1007%2Fs00277-018-3520-5" target="_blank" >https://link.springer.com/article/10.1007%2Fs00277-018-3520-5</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s00277-018-3520-5" target="_blank" >10.1007/s00277-018-3520-5</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30205 - Hematology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2019

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Annals of Hematology

ISSN

0939-5555

e-ISSN

—

Svazek periodika

98

Číslo periodika v rámci svazku

2

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

13

Strana od-do

423-435

Kód UT WoS článku

000456949000018

EID výsledku v databázi Scopus

2-s2.0-85055694223