In T-ALL cells insensitive to Smo inhibition, downregulation of Gli1, enhanced by the inhibition of Akt phosphorylation, results in decreased cell proliferation and survival, further increased by pretreatment with an inhibitor of MEK/ERK signaling, demonstrating the importance of Hh interaction with other pathways [81]. The gene discussed is GLI1; the disease is acute lymphoblastic leukemia.