MiRNA involvement in CLL predisposition. MiRNA alterations can predispose people to CLL development. This proposed model shows structural and/or expression abnormalities of miRNAs in the germline that may represent inherited predisposing events. For simplicity, only gene deletion is shown, but all other types of loss-of-function and gain-of-function mutations described for PCGs can be involved in miRNA disruption (blue color). For CLL to develop, a second genetic event in addition to the predisposing one must occur in a somatic cell (green color). This can be a PCG alteration or a “hit” in another miRNA (presented here as amplification of expression). The consequences of these abnormalities are reflected by the levels of expression of various target mRNAs: overexpression of target oncogenes in the case of miRNA deletion and down-regulation of expression of target TSGs in the case of miRNA amplification.