The homogeneity of the genetic background of a mouse model is an important factor to evaluate the effects of novel therapies. For this reason, we established CLL transplants in syngeneic mice that allowed us at first to propagate, and later to therapeutically treat, the same leukemia in different mice but with the same genetic background. Such a system allows for the study of each leukemia and is a necessary step on the road to find drugs that specifically interfere with the pathways involved in the disease [21, 50]. To determine whether the development of mouse CLL is dependent on the Akt pathway, we investigated whether the disruption of Akt signaling through mTOR, by the mTOR inhibitor rapamycin, prevented or cured mouse CLL. The treatment prolonged the life of all treated animals in either the prevention or the therapeutic group. Mammalian TOR normally regulates translation by regulation key components of the protein synthesis machinery, including ribosomal protein S6 kinase. We found that lymph nodes of untreated mice expressed phosphorylated S6, whereas lymphoid tissues from rapamycin-treated mice did not show any phosphorylation. In conclusion, rapamycin inhibited mTOR activity in the Tcl1-dependent CLL mouse model [50].
