More recently we investigated whether TCL1 expression in CLL is regulated by microRNAs [36]. Since Tcl1 is up-regulated in aggressive CLL, we were interested in microRNAs down-regulated in aggressive CLL that potentially target TCL1. These experiments revealed that expression of miR-29b and miR-181b significantly inhibits Tcl1 expression and that miR-29b and miR-181b target TCL1 expression at mRNA and protein levels [36]. Intriguingly, a microRNA signature was previously reported with 13 microRNAs that differentiate aggressive and indolent CLL [37, 38]. In this signature only four microRNAs were down-regulated in aggressive CLL versus indolent CLL. Remarkably, of the four, three are isoforms of miR-29 (miR-29a-2, miR-29b-2 and miR-29c) [36]. This confirms the importance of the interaction between miR-29 and TCL1 in aggressive CLL.
