Later on, we studied the spontaneous tumor phenotype of Eμ-TCL1 transgenic mice more in detail [50]. An extensive pathologic analysis of these transgenic animals revealed that, in addition to CLL leukemias, more than 30% of mice showed the onset of solid malignant tumors, even though the tumors themselves lacked Tcl1 expression. Secondary malignancies are also frequent complications in patients with CLL [51] and they are the most common cause of death in these patients [52]. Higher risk of secondary non-hematological neoplasms in patients with CLL has several explanations including genetic predisposition, immune deficiency, carcinogen exposure, and the side-effects of therapeutic treatments [53]. In our CLL model, 25% of secondary cancers were malignant pilomatrixoma, a type of skin cancer extremely rare in mice. Thus far, the Eμ-TCL1 model seems to be the only one reported that displays the onset of secondary malignancies in CLL-prone mice [21, 50].
