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DR. KRISTÍNA ZÁPRAŽNÁ

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

Person in Charge: Prof. RNDr. Šárka Pospíšilová, Ph.D.

Host InstitutionResearch group Medical Genomics, Centre for Molecular Medicine, CEITEC, Masaryk University 

Country of Origin: Czech

Previous Place of Work: USA

Project Duration: 36 months

Panel: Life Sciences

Abstract

Activation induced deaminase is a powerful mutator enzyme that initiates 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 leading to cancer-inducing mutations in oncogenes and chromosomal translocations.

Chronic lymphocytic leukemia is an incurable disease with a variable course. The presence of a complex karyotype as well as AID expression are both associated with a bad prognosis. Aberrant expression of alternatively spliced AID transcripts was described in 54% of CLL cases. Given the fact that AID directly causes c-MYC-IGH translocations in Burkitt lymphomas, AID or its splice variants might induce translocations and other chromosomal aberrations that constitute complex karyotype in CLL patients.

In the AIM 1 of this proposal, expression of AID and its splice variants will be correlated with chromosomal aberrations in CLL patients with and without complex karyotype. AIM 2 will address the function of each AID splice variant in normal B cell physiology with the goal to suggest their role in CLL. 

 

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