Model of the p53/miR-34a network and its potential impairment in CLL. DNA damage activates p53 through the activation of ATM. p53 induces cell-cycle arrest through p21 and apoptosis through different targets including Puma. miR-34a is a direct transcriptional target of p53 and in case of a functional pathway, miR-34a will be up-regulated. miR-34a induces cell death through apoptosis and cell-cycle arrest through silencing of its potential targets as cyclin-dependent kinases 4 and 6, CCND1, MYCN, BCL2, and Sirtuin1.^{22,26-33,44,47}  In CLL, different modes of interference in this model occur including mutation/deletion of TP53 and down-regulation of miR-34a.