Self-Renewal of Acute Lymphocytic Leukemia Cells Is Limited by the Hedgehog Pathway Inhibitors Cyclopamine and IPI-926
Figure 2
Hh pathway is active and inhibited by the SMO-inhibitors cyclopamine and IPI-926.
Precursor B-ALL cell lines REH and RS4;11 were transiently transfected with a Gli-responsive luciferase reporter or pGL3-basic, a plasmid lacking GLI binding site, as a negative control. Relative luciferase levels were measured following 48 hours of treatment with vehicle control, purified, dual lipid-modified Shh ligand (Shh-NP), SHh antibody 5E1 (10 µg/ml), cyclopamine (5 µM) or IPI-926 (1 µM). Hh pathway stimulation with SHh (p<0.005) and inhibition with 5E1 (p<0.0001), cyclopamine (p<0.0005) and IPI-926 (p<0.0002) was statistically significant in both the REH and RS4;11 cell lines.