The discovery and role of BCL2 and microRNA in CLL

Carlo Croce, MD of The Ohio State University, Columbus, OH provides an overview of his research on the epigenetics and genetic of chronic lymphocytic leukemia (CLL) while at the 2016 International Workshop of the German CLL Study Group (GCLLSG) in Cologne, Germany. Prof. Croce explains that in 1984, his lab cloned a gene, which they called BCL2. BCL2 turned out to be important because it inhibits the process called programmed cell death or apoptosis. He explains that activation of this gene led to follicular lymphoma. He then was interested in CLL and focused on a specific deletion on chromosome 13 in order to find the gene critical to CLL, which turned out not to be a protein coding gene but a locus encoding two microRNA. Before this finding, as Prof. Croce points out, everybody thought the genes involved in cancer are protein coding genes as the rest of the genome not coding for proteins, was considered ‘garbage’. The genetic loss of this gene encoding the microRNA caused the malignancy. Prof. Croce explains that microRNA are negative regulators of gene expression. The next question was what these short RNA sequences inhibit. The predicted target turned out to be BCL2, meaning that loss of the microRNA would lead to overexpression of BCL2.

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