Figure 6.
JNJ-75276617 exhibits synergistic effects with gilteritinib or venetoclax and azacitidine in AML. (A) KMT2A-r MOLM-13 cells were incubated with the indicated drug combination concentrations for 6 days (JNJ-75276617 and gilteritinib) in technical triplicates. The combination effect was calculated by extended Biochemically Intuitive Generalized Loewe (BIGL) package, with results shown under highest single agent (HSA) null model. Data from 3 independent experiments were pooled and analyzed. Combination effect is represented by the contour plots, with indicating antagonism (red area) and synergy (blue area) as represented by the intensity scale. Dot is proportional to the increase in effect compared with the null, and color intensity is statistical effect. (B) KMT2A-r MOLM-13 cells were treated with JNJ-75276617 for 8 days and venetoclax for 4 days in quadruplicate. The combination effect was calculated by extended BIGL package, with results shown under HSA null model. Data from 2 independent experiments were pooled and analyzed. Combination effect is represented by the contour plots, with indicating antagonism (red area) and synergy (blue area) as represented by the intensity scale. Dot is proportional to the increase in effect compared with the null and color intensity is statistical effect. (C) KMT2A-r MOLM-13 cells were incubated with the indicated drug combination concentrations for 8 days (JNJ-75276617 and azacitidine) and for 4 days (venetoclax) in quadruplicate. The combination effect was calculated by extended BIGL package, with results shown under HSA null model. Data from 2 independent experiments were pooled and analyzed. Combination effect is represented by the contour plots, with indicating antagonism (red area) and synergy (blue area) as represented by the intensity scale. Dot is proportional to the increase in effect compared with the null and color intensity is statistical effect. (D) Mice bearing disseminated MOLM-13 xenografts were treated with JNJ-75276617, venetoclax, azacitidine, or combinations at the dose levels indicated. Lines underneath the x axis indicate the dosing period for each drug. ∗ denotes significant difference (P ≤ .05) in survival compared with the vehicle control group.

JNJ-75276617 exhibits synergistic effects with gilteritinib or venetoclax and azacitidine in AML. (A) KMT2A-r MOLM-13 cells were incubated with the indicated drug combination concentrations for 6 days (JNJ-75276617 and gilteritinib) in technical triplicates. The combination effect was calculated by extended Biochemically Intuitive Generalized Loewe (BIGL) package, with results shown under highest single agent (HSA) null model. Data from 3 independent experiments were pooled and analyzed. Combination effect is represented by the contour plots, with indicating antagonism (red area) and synergy (blue area) as represented by the intensity scale. Dot is proportional to the increase in effect compared with the null, and color intensity is statistical effect. (B) KMT2A-r MOLM-13 cells were treated with JNJ-75276617 for 8 days and venetoclax for 4 days in quadruplicate. The combination effect was calculated by extended BIGL package, with results shown under HSA null model. Data from 2 independent experiments were pooled and analyzed. Combination effect is represented by the contour plots, with indicating antagonism (red area) and synergy (blue area) as represented by the intensity scale. Dot is proportional to the increase in effect compared with the null and color intensity is statistical effect. (C) KMT2A-r MOLM-13 cells were incubated with the indicated drug combination concentrations for 8 days (JNJ-75276617 and azacitidine) and for 4 days (venetoclax) in quadruplicate. The combination effect was calculated by extended BIGL package, with results shown under HSA null model. Data from 2 independent experiments were pooled and analyzed. Combination effect is represented by the contour plots, with indicating antagonism (red area) and synergy (blue area) as represented by the intensity scale. Dot is proportional to the increase in effect compared with the null and color intensity is statistical effect. (D) Mice bearing disseminated MOLM-13 xenografts were treated with JNJ-75276617, venetoclax, azacitidine, or combinations at the dose levels indicated. Lines underneath the x axis indicate the dosing period for each drug. ∗ denotes significant difference (P ≤ .05) in survival compared with the vehicle control group.

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