Expression and function of activation-induced cytidine deaminase splice variants in normal B cell physiology and chronic lymphocytic leukemia (AIDinCLL)
- Project Identification
- Project Period
- 12/2013 - 11/2016
- Investor / Pogramme / Project type
- Incoming grants
- MU Faculty or unit
Central European Institute of Technology
- Mgr. Kristína Zápražná, Ph.D.
Activation induced deaminase (AID) is a powerful mutator enzyme that initiates the production of high affinity antibodies of different isotype classes required for successful management of infections. However this benefit for the organism is counterbalanced by the propensity of AID to deaminate non-specific targets. Mistargeting of AID mutator activity to non-immunoglobulin genes leads to cancer-inducing mutations in oncogenes and chromosomal translocations. Chronic lymphocytic leukemia (CLL) is an incurable disease with a variable course. Numerous prognostic markers were established to identify cases with poor outcome and/or need of immediate treatment: mutational status of IgH variable gene, expression of CD38 and ZAP70, cytogenetic analysis of deletions 13q14, 17p13, 11q22 and trisomy 12 and recently also assessment of karyotype by G-banding. Current research shows that presence of more than three chromosome aberrations as well as expression of AID are both associated with a bad prognosis of B-CLL. Aberrant high expression of alternatively spliced AID transcripts was described in 54% of CLL cases. Given the fact that AID directly causes IgH-c-myc translocations in Burkitt lymphomas, AID or its splice variants could directly induce translocations and other chromosomal aberrations that constitute complex karyotype in CLL patients. In order to address this hypothesis AID expression studies will be conducted on a large cohort of patients and AID knockout mice will be used to test function of AID splice variants and gathered expression and functional data will be correlated to the severity of the disease.
Total number of publications: 5
Activation-induced deaminase and its splice variants associate with trisomy 12 in chronic lymphocytic leukemia
Annals of hematology, year: 2019, volume: 98, edition: 2, DOI
Transcription factor YY1 can control AID-mediated mutagenesis in mice
EUROPEAN JOURNAL OF IMMUNOLOGY, year: 2018, volume: 48, edition: 2, DOI
Activation induced deaminase splice variants expressed in B cell leukemia and lymphoma do not retain their catalytic activity.
Year: 2016, type: Conference abstract
Studium funkčních vlastností sestřihových variant aktivací indukované deaminázy exprimovaných u B buněčných malignit
Klinická onkologie, year: 2016, volume: 29, edition: Supplementum 2
Molecular Evidence for Antigen Drive in the Natural History of Mantle Cell Lymphoma
AMERICAN JOURNAL OF PATHOLOGY, year: 2015, volume: 185, edition: 6, DOI