Fig. 6.

MSCs decreased the anti-leukemia effect of sorafenib via upregulation of autophagy in FLT3-ITD-positive AML cells. A After co-culture with MSCs from case #3, the killing effect of sorafenib in MOLM14 cells decreased significantly, showing as the apoptosis rate of 22.0% ± 2.1% vs. 41.2% ± 2.5% without MSCs (P = 0.014) at 40 nM and 34.8% ± 3.0% vs. 61.9% ± 1.9% (P = 0.008) at 80 nM, respectively. B Immunoblotting analyse showed that, as compared with that without MSCs co-culture, MSCs from case #3 up-regulated the expression of LC3B-II and Beclin-1 and remarkably decreased the inhibition efficacy of sorafenib on FLT3 pathway, especially on FLT3 downstream signaling, including p-FLT3, p-ERK1/2 and p-mTOR, and then decreased the induction of cleaved caspase 3 in MOLM14 cells