Fig. 1.

PRMT5 inhibition leads to a deficiency in cell proliferation, S-phase decrease, increased quiescence, and cell senescence. a) Leukemia cell growth impairment by PRMT5 inhibition. IC₅₀ values for PRMT5 inhibitor GSK591 in EVI1-high, SRSF2 mutant, and other genetic background leukemia patient samples (Other AML). Star indicates p values for SFRSF2mut of 0.016 and p = 0.007 for EVI1-high cells excluding the mutant TP53 sample (open green circle) (Kruskal-Wallis, posthoc Dunn's test). b) Kinetics of cell growth of EVI1-high OCI-AML-20 cells in response to GSK591 (means of 3 replicates shown). c) PRMT5 inhibition results in decreased S-phase frequency (1 μM, GSK591, LLY283, and SGC2096 negative control compound). N = 3, data represented as mean ± SD, *p < 0.05 relative to time-matched control. d) Increased quiescence in EVI-high OCI-AML-20 treated with PRMT5 inhibitors as in C. N = 3, data represented as mean ± SD, *p < 0.05 relative to time-matched control. e) Flow cytometry plots illustrating G₀ quiescent populations for data in d). f) PRMT5 inhibition (GSK591 1 μM) induces senescence in OCI-AML-20 cells as shown by β-galactosidase staining and quantitation on the right (N = 3, all individual data points shown, *p < 0.05, mean ± SD). (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)