Figure 6.
Primary AML from patients with venetoclax-azacitidine–refractory disease respond to venetoclax-gilteritinib in vitro and in vivo. (A) Overview of PDX model experiment. Treatment with gilteritinib (n = 5 mice), venetoclax (n = 5 mice), combination of both (n = 5 mice), or vehicle (n = 4 mice) started 3 weeks postinjection and lasted 4 weeks. Two weeks after end of treatment, mice were euthanized, and bone marrow (BM) was analyzed. (B) Percentage of CD45+ cells in BM obtained from PDX-transformed mice in the fourth week of treatment (left) or after euthanasia (right). (C) Absolute neutrophil count for patients 02 and 70 upon treatment with venetoclax-gilteritinib. (D-G) Percentage of BM (D, F, G) or peripheral blood (E) blasts of 4 venetoclax-azacitidine–refractory patients treated with venetoclax-gilteritinib. Blast percentage was analyzed at indicated time points upon start of the respective treatment condition. (H) Percentage of NPM1 level of patient 05. NPM1 level was analyzed at indicated time points upon start of the respective treatment condition. (I) Blasts from patients 02 and 70 obtained at different stages of therapy were lysed and analyzed for levels of MCL-1 and B-actin. (J) Primary AML blasts from patient 01 were treated for 12 hours with 100 nM of venetoclax, 500 nM of gilteritinib, or the combination of both. MCL-1 and B-actin levels were detected by western blotting and compared with untreated cells. ∗P < .05.

Primary AML from patients with venetoclax-azacitidine–refractory disease respond to venetoclax-gilteritinib in vitro and in vivo. (A) Overview of PDX model experiment. Treatment with gilteritinib (n = 5 mice), venetoclax (n = 5 mice), combination of both (n = 5 mice), or vehicle (n = 4 mice) started 3 weeks postinjection and lasted 4 weeks. Two weeks after end of treatment, mice were euthanized, and bone marrow (BM) was analyzed. (B) Percentage of CD45+ cells in BM obtained from PDX-transformed mice in the fourth week of treatment (left) or after euthanasia (right). (C) Absolute neutrophil count for patients 02 and 70 upon treatment with venetoclax-gilteritinib. (D-G) Percentage of BM (D, F, G) or peripheral blood (E) blasts of 4 venetoclax-azacitidine–refractory patients treated with venetoclax-gilteritinib. Blast percentage was analyzed at indicated time points upon start of the respective treatment condition. (H) Percentage of NPM1 level of patient 05. NPM1 level was analyzed at indicated time points upon start of the respective treatment condition. (I) Blasts from patients 02 and 70 obtained at different stages of therapy were lysed and analyzed for levels of MCL-1 and B-actin. (J) Primary AML blasts from patient 01 were treated for 12 hours with 100 nM of venetoclax, 500 nM of gilteritinib, or the combination of both. MCL-1 and B-actin levels were detected by western blotting and compared with untreated cells. ∗P < .05.

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