MicroRNA dysregulation to identify novel therapeutic targets

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This paper describes how we discovered the juxtaposition of the MYC gene to the human immunoglobulin loci and how that finding was extended to characterize molecularly the t(14;18) chromosome translocation of follicular lymphoma and to clone the BCL2 gene. BCL2 is also overexpressed in CLL, the most common human leukemia. We discovered that most of human CLLs have a deletion of two microRNAs residing in the same polycistronic RNA, miR-15a and miR-16-1, and that these two microRNAs are negative regulators of BCL2. Thus, loss of miR-15/16 leads to overexpression of BCL2 that can be targeted by the new drug, venetoclax, that was recently approved by the FDA for the treatment of aggressive CLLs.




Croce, C. M. (2017). MicroRNA dysregulation to identify novel therapeutic targets. In Current Topics in Microbiology and Immunology (Vol. 407, pp. 191–203). Springer Verlag. https://doi.org/10.1007/82_2017_34

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