The mechanisms responsible for HMA resistance are unknown, but an RNAi-based screen in AML cells identified several HH pathway components (SMO, SHH, and GLI3) that were associated with 5-azacytidine resistance, and the combination of the SMO inhibitor sonidegib with 5-Aza led to synergistic cell killing [40]. This evidence concerns the gene GLI3 and acute myeloid leukemia.