Project information

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

Project Identification
3SGA5792
Project Period
12/2013 - 11/2016
Investor / Pogramme / Project type
South-Moravian Region
MU Faculty or unit
Central European Institute of Technology

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.

Publications

Total number of publications: 5