The Hedgehog pathway as targetable vulnerability with 5-azacytidine in myelodysplastic syndrome and acute myeloid leukemia

Table 4 Sequential versus concurrent 5-azacytidine/LDE225 treatment

Cell line	LDE225 dose and sequence of drug dosing
	32 μM LDE225			8 μM LDE225			2 μM LDE225
	5-Aza + LDE225	LDE225→5-Aza	5-Aza→LDE225	5-Aza + LDE225	LDE225→5-Aza	5-Aza→LDE225	5-Aza + LDE225	LDE225→5-Aza	5-Aza→LDE225
TF-1	1.3	−1.5	1	1.2	−1.6	−1.2	1.3	−1.1	−1.1
OCI-AML3	2.6	−2	−1.5	2	−1.8	−1.7	1.3	−1.3	−1.2
MDS-L	1.5	−1.6	−1.2	1.5	−1.1	−1.2	1.1	−1.2	−1.2
THP-1	2	−1	−1.1	2	−1.5	−1.3	1.1	−1.3	−1.2

Fold-shift of EC₅₀ values at sequential (5-Aza first followed by LDE-225: 5-Aza→LDE225; LDE225 first followed by 5-Aza: LDE225→5-Aza) or concurrent (5-Aza + LDE225) treatment in four AML cell lines. Fold-shift is calculated by comparing the 5-Aza EC50 value in the combination of 5-Aza + LDE225 to the EC50 value of 5-Aza alone

ISSN: 1756-8722