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. 2022 Jan 27;12:820191. doi: 10.3389/fphar.2021.820191

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Copyright © 2022 Tregnago, Benetton, Da Ros, Borella, Longo, Polato, Francescato, Biffi and Pigazzi.

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Combination treatments in 3D model. (A) Scheme of the in vitro 3D culture setup procedure: hydroxyapatite/collagen scaffolds were allowed to soak for 24 h, then seeded with acute myeloid leukemia (AML)-MSCs (t = 1), and cultured for a further 5 days prior to adding of KMT2A-rearranged AML cells and performing the drug treatment (t = 6). Cell viability was evaluated in the 3D system at 48 h after treatment (t = 8) by ATP 3D assay. (B–D) Cell viability of 3D system analyzed at 48 h after drug treatment with venetoclax (1 μM), I-BET151 (2 μM), sunitinib (5 µM), and thioridazine (10 μM) normalized to the respective controls (dimethyl sulfoxide; n = 3) in SHI-1 and NOMO-1 cell lines (B, C) and AML primary samples (D, E). CI, combination index; synergy when CI <1. ANOVA test was performed by applying Bonferroni correction for multiple statistical hypotheses testing. *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001.