dactolisib and show it has a striking impact on the frequency of leukemia cells in the blood, significantly
prolonging mouse survival. To identify novel targeted agents against mutant IL7R dependence, we
performed a chemical screen on Ba/F3 cells ectopically expressing mutant IL-7Rα. We demonstrate
that 2 distinct new generation sphingosine kinase inhibitors are effective against mutant IL7R mouse
B-ALLs both in vitro and in vivo. Importantly, we validated our findings in IL7R mutant primary human
B-ALLs.
Conclusion: Our studies provide a novel, powerful in vivo resource to explore the pathophysiology and
therapeutic vulnerabilities of B-ALL, and demonstrate for the first time that IL7R can initiate this
malignancy.
`
