Fig. 8

FTO regulates leukemogenesis and sensitivity of t(8;21) AML cells to Ara-C through IGFBP2. A Western blotting for the expression of IGFBP2 in SKNO-1 and Kasumi-1 cells transduced with shNS (pLKO.1-shNS + empty pTSB), shFTO (pLKO.1-shFTO#1 + empty pTSB), shFTO + IGFBP2 (pLKO.1-shFTO#1 + pTSB-IGFBP2-CDS), or IGFBP2 (pLKO.1-shNS + pTSB-IGFBP2-CDS). shNS, scramble shRNA. B CCK-8 assays for the effects of FTO knockdown and/or overexpression of IGFBP2 on the proliferation of SKNO-1 and Kasumi-1 cells. C Effects of FTO knockdown with IGFBP2 overexpression on colony-forming capacity of SKNO-1 and Kasumi-1 cells. D CCK-8 assays for the effects of FTO knockdown and/or overexpression of IGFBP2 on the sensitivity to Ara-C in SKNO-1 and Kasumi-1 cells. E–G Effects of FTO knockdown with IGFBP2 overexpression on AML1-ETO9a-driven AML mice. Western blot analysis for Igfbp2 and Fto (E), Wright-Giemsa staining of bone marrow and H&E staining of livers and spleens (F) and flow cytometric analysis of the abundance of GFP⁺ AML1-ETO9a AML cells in PB, BM and SP (G) were shown. H Proposed model depicting the regulatory interactions and role of FTO in leukemogenesis and Ara-C resistance in t(8;21) AML.