Principle Investigator: Benjamin Mizukawa, MD

Benjamin Mizukawa, MD, of Cincinnati Children's.Previous work implicates Epstein-Barr virus (EBV) in pathogenesis of autoimmune diseases, chronic lymphocytic leukemia (CLL), and other lymphocyte disorders. From our search for transcription factors (TFs) that concentrate in the genetic loci of acute lymphoblastic leukemia (ALL), we find EBNA3, encoded by the EBV genome, and EP300, NR3C1 and FOXO1 encoded by the human genome, to be enriched at ALL loci (RR>14, Pc<10^-6). Existing literature reports about a 20% higher frequency of EBV infection in ALL cases suggesting ~20% of childhood ALL may be EBV-associated.

We are working to identify the EBV-infected cases in Cincinnati Children’s ALL patients, to characterize their genomics and distinguishing clinical features, and to identify chemicals that interfere with EBNA3 expression at ALL risk loci. This work will provide the preliminary data to use subsequent experiments to establish whether these EBV-related associations are non-specific for infection or are EBV-specific mechanisms of ALL pathogenesis.