The HH pathway is important to normal hematopoiesis and is both lineage and stage dependent and disruption of the HH pathway has been found in many hematologic malignancies, with a strong relation to MDS and progression into AML.57,167,168 Studies have found that myeloid malignancies express higher levels of HH proteins and their downstream targets with the majority of AML patient samples overexpressing SHH, PTCH-1, SMO, and/or GLI family proteins.169 Importantly, GLI1 expression has been found to be elevated in the blasts of relapsed AML patients. Here, GLI1 is linked to acute myeloid leukemia.