Fig 2: Gilteritinib and Venetoclax induce apoptosis/cell death of FLT3/ITD cells. a Bar graph of 48 h apoptosis/cell death assay of Molm14, Molm14-R, MV4;11, THP-1, HL-60, and U937 cells. (Gilteritinib: 80 nM, Venetoclax: 20 nM, Combo: Gilteritinib 80 nM + Venetoclax 20 nM), b Bar graph of 48 h apoptosis/cell death assay of primary FLT3/ITD AML patient sample #2 treated with the indicated concentration of Gilteritinib and Venetoclax. c–g Bar graphs of cell cycle analysis of Molm14, Molm14-R, MV4;11, MV4;11-R, and U937 treated cells

Fig 3: The effects of FLT3 TKI (Gilteritinib or Sorafenib) and/or Venetoclax treatment in BaF3 cells with FLT3 AL point mutations. In all, 48 h MTT assay of a BaF3 D835N, c BaF3 D835L+K, e BaF3 D835E, and g BaF3 D835Y cells treated with indicated doses of Gilteritinib and/or Venetoclax. In all, 48 h MTT assay of b BaF3 D835N, d BaF3 D835L+K, f BaF3 D835E, and h BaF3 D835Y treated with indicated doses of sorafenib and/or Venetoclax

Fig 4: Gilteritinib and Venetoclax synergistically inhibit the proliferation of FLT3/ITD cell lines and primary FLT3/ITD AML samples. 48 h MTT assay of cells treated with the indicated doses of Gilteritinib and Venetoclax: a Molm14, b Molm14 cells resistant to 60 nM Lestaurtinib (Molm14-R), c MV4;11, d HL-60, e THP-1, f U937, g Primary de novo AML patient samples with FLT3/ITD mutation (AML-ITD#1, AML-ITD#2, AML-ITD#3), h Primary AML samples from relapsed patients with FLT3/ITD mutations (Relapse ITD AML #1, Relapse ITD AML #2, Relapse ITD AML #3), i Primary AML patients with FLT3/TKD mutation, or j without FLT3 mutations (AML-WT#1, AML-WT#2)

Fig 5: Gilteritinib and Venetoclax combine to more effectively eliminate FLT3/ITD cells in vivo. Mice were treated with vehicle, Gilteritinib (15 mg/kg/day), Venetoclax (80 mg/kg/day), or the combination via oral gavage for various length of time. a, b Engraftment in BM and Kaplan–Meier survival curve for Molm14-R transplanted mice; c, d Engraftment in PB and Kaplan–Meier survival curve for FLT3/ITD;NHD13 transplanted mice; e Engraftment of human CD45 + cells in the BM of PDX mice