In the last few years, several important studies uncovering molecular mechanisms of CLL pathogenesis were reported. In addition to miR-15/16 targeting BCL2, DLEU7 was identified as second tumor suppressor at 13q14 [20]. Also, we demonstrated that Tcl1 functions as a transcriptional regulator in the pathogenesis of aggressive CLL [23]. Importance of miR-15/16 and TCL1 in CLL was supported by generating TCL1 transgenic and miR-15/16 knockout mouse models, both showing CLL phenotype. Activation of NF-kB pathway has evolved as another critical event in CLL pathogenesis since NF-kB is activated in three CLL mouse models, APRIL driven, BCL2 and TRAF2 driven, and TCL1 driven (Tcl1 functions as NF-kB activator) (Figure 1).
