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

Zaprazna, Kristina; Réblová, Kamila; Svobodová, Veronika; Radová, Lenka; Bystrý, Vojtěch; Baloun, Jiří; Ďurechová, Kristina; Tom, Nikola; Loja, Tomáš; Burešová, Martina; Stránská, Kamila; Oltová, Alexandra; Doubek, Michael; Atchison, Michael L.; Trbušek, Martin; Malčíková, Jitka; Pospı́šilová, Šárka

doi:10.1007/s00277-018-3520-5

Cited by 2 publications

(3 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There are no reports suggesting that the aicda gene is mutated in CLL, as is the case in Hyper-IgM Syndrome, type 2. However, the splice variants mentioned above that have been found in normal B lymphocytes have also been detected in CLL by our ( 124 , 125 ) and other ( 25 , 123 , 170 – 172 ) laboratories. Furthermore, like normal human B lymphocytes, CLL B cells express only a single variant form of AID mRNA ( 25 ), although this might change with environmental input.…”

Section: Activation-induced Deaminase In Cll Cells and Its Effects On Cll-cell Biologysupporting

confidence: 63%

“…Despite these findings, a recent study suggested that AID splice variant proteins are not functional (172), which might be expected since AID splice variant patterns are not different at the time of diagnosis, nor do they appear to have an impact on progression-free and overall survival (171). Favoring this hypothesis, the work of Rebhandl et al proposed that despite the presence of alternatively spliced AID transcripts, only full-length AID was detected at the protein level (173).…”

Section: Activation-induced Deaminase In Cll Cells and Its Effects On Cll-cell Biology Aid Molecular And Structural Considerations In Cllmentioning

confidence: 99%

“…In a cohort of 149 patients, higher levels of alternatively spliced transcripts of AID (AIDΔE4a, AIDΔE4, AIDivs3, and AIDΔE3E4) were associated with 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 ( 25 , 172 ).…”

Section: Activation-induced Deaminase In Cll Cells and Its Effects On Cll-cell Biologymentioning

confidence: 99%

See 2 more Smart Citations

AID in Chronic Lymphocytic Leukemia: Induction and Action During Disease Progression

2021

View full text Add to dashboard Cite

The enzyme activation-induced cytidine deaminase (AID) initiates somatic hypermutation (SHM) and class switch recombination (CSR) of immunoglobulin (Ig) genes, critical actions for an effective adaptive immune response. However, in addition to the benefits generated by its physiological roles, AID is an etiological factor for the development of human and murine leukemias and lymphomas. This review highlights the pathological role of AID and the consequences of its actions on the development, progression, and therapeutic refractoriness of chronic lymphocytic leukemia (CLL) as a model disease for mature lymphoid malignancies. First, we summarize pertinent aspects of the expression and function of AID in normal B lymphocytes. Then, we assess putative causes for AID expression in leukemic cells emphasizing the role of an activated microenvironment. Thirdly, we discuss the role of AID in lymphomagenesis, in light of recent data obtained by NGS analyses on the genomic landscape of leukemia and lymphomas, concentrating on the frequency of AID signatures in these cancers and correlating previously described tumor-gene drivers with the presence of AID off-target mutations. Finally, we discuss how these changes could affect tumor suppressor and proto-oncogene targets and how they could be associated with disease progression. Collectively, we hope that these sections will help to better understand the complex paradox between the physiological role of AID in adaptive immunity and its potential causative activity in B-cell malignancies.

show abstract

Section: Activation-induced Deaminase In Cll Cells and Its Effects On Cll-cell Biologysupporting

confidence: 63%

Section: Activation-induced Deaminase In Cll Cells and Its Effects On Cll-cell Biology Aid Molecular And Structural Considerations In Cllmentioning

confidence: 99%

Section: Activation-induced Deaminase In Cll Cells and Its Effects On Cll-cell Biologymentioning

confidence: 99%

See 1 more Smart Citation

AID in Chronic Lymphocytic Leukemia: Induction and Action During Disease Progression

2021

View full text Add to dashboard Cite

show abstract

Stepwise generation of AID knock-in and conditional knockout mice from a single gene-targeting event

Kinoshita

Uemura

Shimizu

et al. 2021

International Immunology

View full text Add to dashboard Cite

Activation-induced cytidine deaminase (AID) encoded by the Aicda gene initiates class-switch recombination and somatic hypermutation of immunoglobulin genes. In addition to this function, AID is also implicated in the epigenetic regulation in pluripotent stem cells and in the oncogenesis of lymphoid and non-lymphoid origins. To examine AID’s role in specific cell types, we developed mouse strains of conditional knockout (Aicda-FL) and knock-in with a red fluorescent protein gene (RFP) inserted into the Aicda locus (Aicda-RFP). These two strains were obtained from a single targeting event in embryonic stem cells by a three-loxP or tri-lox strategy. Partial and complete recombination among the three loxP sites in the Aicda-RFP locus gave rise to Aicda-FL and AID-deficient loci (Aicda-KO), respectively, after mating Aicda-RFP mice with Cre-expressing mice driven by tissue-non-specific alkaline phosphate promoter. We confirmed RFP expression in B cells of germinal centers of intestine-associated lymphoid tissue. Mice homozygous for each allele were obtained and were checked for AID activity by class-switch and hypermutation assays. AID activity was normal for Aicda-FL but partially and completely absent for Aicda-RFP and Aicda-KO, respectively. Aicda-FL and Aicda-RFP mice would be useful for studying AID function in subpopulations of B cells and in non-lymphoid cells.

show abstract

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

Cited by 2 publications

References 58 publications

AID in Chronic Lymphocytic Leukemia: Induction and Action During Disease Progression

AID in Chronic Lymphocytic Leukemia: Induction and Action During Disease Progression

Stepwise generation of AID knock-in and conditional knockout mice from a single gene-targeting event

Contact Info

Product

Resources

About