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. 2021 Sep 25;24(10):103173. doi: 10.1016/j.isci.2021.103173

Figure 4.

Figure 4

AKT and ERK critically mediate SLFN11 expression in GOF mutant leukemic cells

(A) Phosphorylation status of AKT and ERK detected by Western blotting on the steady-state condition. The red rectangle indicates the leukemic cells with GOF mutation in TYK2.

(B) Alteration of phosphorylated-AKT and -ERK by cerdulatinib (40 μM) was measured by Western blotting at the indicated time points.

(C) Phosphorylation status of AKT after release of cerdulatinib (40 μM, 24 h) in MOLT4 cells.

(D) Alteration of phosphorylated-AKT and -ERK in HEL cells by cerdulatinib (40 μM) was measured by Western blotting at the indicated time points.

(E) SLFN11 protein expression detected by Western blotting in CCRF-CEM cells treated with LY294002 (20 μM, PI3K inhibitor) and/or SCH772984 (20 μM, ERK inhibitor) for 24 h.

(F) SLFN11 protein expression in CCRF-CEM cells treated with MK-2206 (20 μM, AKT inhibitor) and/or SCH772984 (20 μM, ERK inhibitor) for 24 h.

(G) Quantitation of SLFN11 protein expression in 3 independent experiments as shown in Figure 4F (CCRF-CEM) and S4B (MOLT4). The error bars represent SD; ∗p = 0.012 (CCRF-CEM), ∗p = 0.026 (MOLT4), ∗∗p = 0.007, ∗∗∗p < 0.001 with ordinary one-way ANOVA test and Tukey’s multiple comparisons test.