As we reported in the previous chapter, levels of TCL1 expression in CLL are regulated by miR-29 and mir-181 that target 3′ UTR of TCL1. To determine whether treatment with microRNAs targeting TCL1 can inhibit CLL in mice, we designed TCL1 transgenic mice using a construct containing the 3′ and 5′ UTRs of TCL1 under B cell – specific Eμ promoter (Eμ-TCL1 Full Length). At the age of 16–20 months, these mice showed a CLL-like disease [54]. Immunophenotyping revealed accumulation of CD5+ CD23+ B220+ population in spleens and lymph nodes. Our findings showed that CD5+ CD23+ B cell populations from Eμ-TCL1FL mice actively proliferated and showed significantly increased levels of phospho-Akt. Eμ-TCL1FL mice showed immunological abnormalities similar to those present in human CLL, including hypoimmunoglobulinemia, abnormal levels of cytokines and impaired immune response. Overall, these results revealed biochemical and immunological similarities to Tcl1 driven CLL mouse models and human CLL [54].
