To elucidate whether such mutations in XPO1 could play a causal role in CLL leukemogenesis, we developed Eμ-XPO1 transgenic mice harboring human XPO1 under control of μ heavy chain enhancer (Eμ) elements driving constitutive expression of XPO1. We found that overexpression of XPO1 (wt, E571K or E571G) was sufficient to initiate development of a CLL-like disease in a subset of aged mice, but lacked the ability to drive a spontaneous leukemic expansion in young mice. The gene discussed is XPO1; the disease is B-cell chronic lymphocytic leukemia.