Fig. 4: Igf2bp3 promotes murine AML initiation and development.

A Schematic illustration of the in vivo primary BMT assay and in vitro CFA with HSPCs co-transduced with MA9 retroviruses and Igf2bp3 shRNA (or shNS) lentiviruses. B Kaplan–Meier curves showing the effect of Igf2bp3 KD on MA9-induced leukemogenesis. C Wright-Giemsa staining of BM cells and PB blood smear, and hematoxylin and eosin (H&E) staining of livers and spleens of the representative primary BMT mice from (B) at the endpoint. Scale bars from left to right: 20 μm, 50 μm, 200 μm, 300 μm. D, E CFA using mouse HSPCs transduced with MA9 (D) or PML-RARa (E) plus shNS, Bp3-sh1, or Bp3-sh2 viruses. F HSPCs from FLT3-ITD/NPM1-mut mice were transduced with shNS, Bp3-sh1, or Bp3-sh2 viruses and seeded for CFA. Bar = 200 μm. G HSPCs from Mettl14^fl/fl-CRE^ERT mice were transduced with MA9 retroviruses and seeded for CFA. Mettl14 KO was induced by addition of 4-Hydroxytamoxifen (4-OHT, 1 mM) during plating. H Schematic illustration of the in vivo primary BMT assay and in vitro CFA with HSPCs from Igf2bp3 WT and KO mice. I Colony numbers and representative photos of colonies in the CFA assays illustrated in (H). Bar = 200 μm. J Flow cytometric analysis of CD45.2⁺ donor cell percentages in PB of recipient mice 8 weeks after BMT. n = 7 mice. K Kaplan–Meier curves showing the effect of Igf2bp3 KO on MA9-induced leukemogenesis. L, M Representative images of liver (L) and spleen (M) tissues from the primary BMT mice in (K) at the endpoint. N Wright-Giemsa staining of BM cells and PB blood smear, and H&E staining of livers and spleens of representative primary BMT recipient mice from (K) at the endpoint. Scale bars are same as in (C). O HSPCs from WT or Igf2bp3 KO mice were co-transduced with MA9 and ATF4-, PHGDH-, or PSAT1-overexpressing viruses and seeded for CFA. P Schematic illustration of the secondary BMT assay and CFA with MA9-induced leukemic cells transduced with Igf2bp3 shRNA (or shNS) lentiviruses. Q CFA assays showing the effect of Igf2bp3 KD on BM cells from MA9 leukemia mice. Bar = 200 μm. R Kaplan–Meier curves showing the result of secondary BMT using cells collected from the first plating of (O). Representative results from one of at least two mice were shown (C, N). Mean ± SD values are shown. n = 2 biologically independent repeats in (D, E, F, G, I, O, and Q). Statistical analysis: Two-tailed student’s t-test (J); log-rank test (B, K, and R). Source data are provided as a Source Data file.