The first evidence for miRNAs involvement in human cancer was indeed from a study on CLL: 13q14.3 deletion, frequently observed in the patients, was shown to remove two microRNA genes, miR-15 and miR-16; their loss causes deregulation of BCL2.5, 48, 49, 50 Subsequent studies, with the support of the TCL1-tg mouse model, disclosed an involvement of p53-miR15/16-MCL1 axis in the regulation of resistance.51 Loss of p53 in TCL1-tg/p53−/− crossed mice causes a decrease of miR15/16 together with an upregulation of MCL1 and the consequent development of a more severe CLL. This evidence concerns the gene BCL2 and B-cell chronic lymphocytic leukemia.