Age and Sex Differences in the Eμ-TCL1 Adoptive Transfer Mouse Model of CLL

Abstract Background:The Eμ-TCL1 syngeneic model is the most widely used mouse model of chronic lymphocytic leukemia and has been extensively used to understand the pathogenesis of select genes, the effect of the immune microenvironment and for pre-clinical drug development studies. Recently there has been an increasing awareness of the impact of age and sex differences on not only the development of cancers but also the efficacy and toxicity of specific cancer therapies. However, despite the predominance of older males in CLL patient demographics, the Eμ-TCL1 adoptive transfer studies have used almost exclusively young female recipient mice. Methods:In this study we performed primary and secondary adoptive transfer experiments in order to understand the impact of recipient age and sex on the development of disease as assessed by flow cytometry and survival in the Eμ-TCL1 adaptive transfer model. Results:We found that young female recipients had pro-longed survival in a primary adoptive transfer, however sex differences were not observed in a subsequent secondary adoptive transfer experiment. Furthermore, while recipient age did not have a significant effect on the rate of disease establishment or survival in female mice, aged male mice had a significantly decreased rate of Eμ-TCL1 tumor engraftment. Conclusions:These findings suggest that age and sex differences must be considered in the experimental design of studies using the Eμ-TCL1 adaptive transfer model of CLL.