Human CD34⁺ progenitor cells transduced and xenotransplanted in NSG mice develop into AML. (A) Schematic representation of the experimental approach to generate the human CD34⁺ progenitor mouse model carrying the CNTRL-FGFR1 fusion gene. (B) Kaplan-Meier survival analysis of primary recipients following engraftment of either the MIEG3 control vector or CNTRL-FGFR1-transduced human CD34⁺ progenitor cells. (C) Representative flow cytometry analysis of BM, PB, SP, and liver (LV) cells from a primary recipient mouse. (D) Quantitative RT-PCR analysis shows the comparison of gene expression levels in CNTRL-FGFR1 mice (CNTRL) and 1 CNTRL-FGFR1 patient compared with an MIEG3-NSG (MIEG3) mouse and normal healthy human PB mononuclear cells (Nor. PBMN), respectively. (E) Western blot analysis shows the gene expression levels of activated FGFR1, MYC, and GFI1 in leukemic mouse spleens compared with normal human PBMN. (F) Flow cytometry analysis of FLT3 and KIT expression on the cell surface from the CNTRL-FGFR1-NSG (CNTRL) and control MIEG3-NSG (MIEG3) mice. (G) Cell viability assays show the synergistic effect of ponatinib (Pon) and JQ1 on cell growth inhibition in different primary leukemic mouse splenocytes and normal PBMN cells. (H) Western blot analysis shows the MYC, FGFR1, or FGFROP2-FGFR1 fusion protein levels in 4 human AML cell lines (left). Cell viability assays show the synergistic effect of Pon and JQ1 on cell growth inhibition is only seen in KG-1 cells that carry an FGFR1 rearrangement (right).