Fig. 6: Induction of KLF2 by UM171 inhibit cell proliferation in culture.
A Treatment of HEL cells with UM171 (6 μM) induces KLF2 expression, as determined by Q-RT-PCR. B KLF2 induction was partially blocked by treatment with LGH447 (5 μM), as determined by western blot. C Inhibition of KLF2 expression in HEL cells using shRNA constructs (KLF2-sh1, KLF2-sh2, KLF2-sh3), as determined by Q-RT-PCR. D Induction of KLF2 by UM171 was moderated in KLF2-sh2 cells, determined by Q-RT-PCR. E KLF2 knockdown moderated suppression of KLF2-sh2 cell proliferation by UM171 when compared to the control scrambled cells. F Growth suppression by UM171 was further accelerated when co-treated with LGH447(5 μM) in the culture of HEL cells. G Depicted diagram of growth suppression by UM171. UM171 through binding to PIM1 activates HSCE markers and cancer stemness by increasing cancer stem cells (CSCs) and via unknown target increases the expression of P21cip1 and KLF2, leading to growth suppression. Cancer stemness induction by UM171 may partially interfere with growth suppression by UM171 and blocking CSC by a pan-PIM inhibitor should further accelerate leukemia inhibition by the compound.
