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

J 2019

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

ZÁPRAŽNÁ, Kristína, Kamila RÉBLOVÁ, V. SVOBODOVA, Lenka RADOVÁ, Vojtěch BYSTRÝ et. al.

Basic information

Original name

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

Authors

ZÁPRAŽNÁ, Kristína (203 Czech Republic, belonging to the institution), Kamila RÉBLOVÁ (203 Czech Republic, belonging to the institution), V. SVOBODOVA (203 Czech Republic), Lenka RADOVÁ (203 Czech Republic, belonging to the institution), Vojtěch BYSTRÝ (203 Czech Republic, belonging to the institution), Jiří BALOUN (203 Czech Republic, belonging to the institution), Kristina ĎURECHOVÁ (203 Czech Republic, belonging to the institution), Nikola TOM (203 Czech Republic, belonging to the institution), Tomáš LOJA (703 Slovakia, belonging to the institution), Martina BUREŠOVÁ (203 Czech Republic, belonging to the institution), Kamila STRÁNSKÁ (203 Czech Republic, belonging to the institution), Alexandra OLTOVÁ (203 Czech Republic, belonging to the institution), Michael DOUBEK (203 Czech Republic, belonging to the institution), M.L. ATCHISON (840 United States of America), Martin TRBUŠEK (203 Czech Republic, belonging to the institution), Jitka MALČÍKOVÁ (203 Czech Republic, belonging to the institution) and Šárka POSPÍŠILOVÁ (203 Czech Republic, guarantor, belonging to the institution)

Edition

Annals of hematology, New York, Springer Verlag, 2019, 0939-5555

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30205 Hematology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 2.904

RIV identification code

RIV/00216224:14740/19:00109169

Organization unit

Central European Institute of Technology

DOI

http://dx.doi.org/10.1007/s00277-018-3520-5

UT WoS

000456949000018

Keywords in English

Activation induced deaminase; Chronic lymphocytic leukemia; Complex karyotype; Alternative splicing; Trisomy 12

Abstract

V originále

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.

Links

LM2011020, research and development project

Name: CEITEC ? open access

Investor: Ministry of Education, Youth and Sports of the CR

LQ1601, research and development project

Name: CEITEC 2020 (Acronym: CEITEC2020)

Investor: Ministry of Education, Youth and Sports of the CR

3SGA5792, interní kód MU

Name: Expression and function of activation-induced cytidine deaminase splice variants in normal B cell physiology and chronic lymphocytic leukemia (Acronym: AIDinCLL)

Investor: South-Moravian Region, Incoming grants

90091, large research infrastructures

Name: NCMG

Citovat

ZÁPRAŽNÁ, Kristína, Kamila RÉBLOVÁ, V. SVOBODOVA, Lenka RADOVÁ, Vojtěch BYSTRÝ, Jiří BALOUN, Kristina ĎURECHOVÁ, Nikola TOM, Tomáš LOJA, Martina BUREŠOVÁ, Kamila STRÁNSKÁ, Alexandra OLTOVÁ, Michael DOUBEK, M.L. ATCHISON, Martin TRBUŠEK, Jitka MALČÍKOVÁ and Šárka POSPÍŠILOVÁ. Activation-induced deaminase and its splice variants associate with trisomy 12 in chronic lymphocytic leukemia. Annals of hematology. New York: Springer Verlag, 2019, vol. 98, No 2, p. 423-435. ISSN 0939-5555. Available from: https://dx.doi.org/10.1007/s00277-018-3520-5.

@article{1498916,
   author = {Zápražná, Kristína and Réblová, Kamila and Svobodova, V. and Radová, Lenka and Bystrý, Vojtěch and Baloun, Jiří and Ďurechová, Kristina and Tom, Nikola and Loja, Tomáš and Burešová, Martina and Stránská, Kamila and Oltová, Alexandra and Doubek, Michael and Atchison, M.L. and Trbušek, Martin and Malčíková, Jitka and Pospíšilová, Šárka},
   article_location = {New York},
   article_number = {2},
   doi = {http://dx.doi.org/10.1007/s00277-018-3520-5},
   keywords = {Activation induced deaminase; Chronic lymphocytic leukemia; Complex karyotype; Alternative splicing; Trisomy 12},
   language = {eng},
   issn = {0939-5555},
   journal = {Annals of hematology},
   title = {Activation-induced deaminase and its splice variants associate with trisomy 12 in chronic lymphocytic leukemia},
   url = {https://link.springer.com/article/10.1007%2Fs00277-018-3520-5},
   volume = {98},
   year = {2019}
}

TY  - JOUR
ID  - 1498916
AU  - 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
PY  - 2019
TI  - Activation-induced deaminase and its splice variants associate with trisomy 12 in chronic lymphocytic leukemia
JF  - Annals of hematology
VL  - 98
IS  - 2
SP  - 423-435
EP  - 423-435
PB  - Springer Verlag
SN  - 09395555
KW  - Activation induced deaminase
KW  - Chronic lymphocytic leukemia
KW  - Complex karyotype
KW  - Alternative splicing
KW  - Trisomy 12
UR  - https://link.springer.com/article/10.1007%2Fs00277-018-3520-5
L2  - https://link.springer.com/article/10.1007%2Fs00277-018-3520-5
N2  - 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.
ER  -

ZÁPRAŽNÁ, Kristína, Kamila RÉBLOVÁ, V. SVOBODOVA, Lenka RADOVÁ, Vojtěch BYSTRÝ, Jiří BALOUN, Kristina ĎURECHOVÁ, Nikola TOM, Tomáš LOJA, Martina BUREŠOVÁ, Kamila STRÁNSKÁ, Alexandra OLTOVÁ, Michael DOUBEK, M.L. ATCHISON, Martin TRBUŠEK, Jitka MALČÍKOVÁ and Šárka POSPÍŠILOVÁ. Activation-induced deaminase and its splice variants associate with trisomy 12 in chronic lymphocytic leukemia. \textit{Annals of hematology}. New York: Springer Verlag, 2019, vol.~98, No~2, p.~423-435. ISSN~0939-5555. Available from: https://dx.doi.org/10.1007/s00277-018-3520-5.

Detailed Information on Publication Record