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TP53 mut/mut-like AMLs are associated with increased susceptibility to ferroptosis-induced cell death (A) Violin plots displaying the ES for the REACTOME_ACTIVATION_GENE_EXPRESSION_BY_SREBF_SREBP (left side) and the gene expression levels (transcripts per million, TPM) for the SREBP-related genes ( SCD and HMGCS1 ) for AML patients included in the TCGA cohort ( n = 173). Patients were categorized according to the TP53 mutational status into TP53 wt, TP53 mut-like, and TP53 mut. (B and C) Relative mRNA expression levels of Δ Np73 , CEBPA/CEBPB , and its related targets at baseline and upon dipyridamole (DP) treatment (10 μM) in MOLM13 ΔNp73-OE/EV (pMEG) cells (48 h) (B) and at baseline in MOLM13-KO/Scr control cells (C) ( n = 4). (D) Drug-induced apoptosis in MOLM13 and MV4-11 cells (ΔNp73-OE and EV control) treated with ferroptosis-related <t>drugs</t> <t>KPT-9274</t> (NAMPT inhibitor ) and DP alone or in combination with VEN (concentrations indicated in the plots, 72 h) detected by flow cytometry. (E and F) Drug-induced apoptosis (E) and total ROS levels (F) in MOLM13 cells (ΔNp73-OE and EV control) treated with the GPX4 inhibitors RSL3 and ML210 (concentrations indicated in the plots, 72 h) detected by flow cytometry. (G) Viable cell counts of MOLM13 cells (ΔNp73-OE and EV control) treated with the SCD inhibitor MK-8245 (concentrations indicated in the plots, 72 h) detected by flow cytometry ( n = 4). Data are reported as mean ± SEM for (B)–(G). The p values and cell types are indicated in the graphs; ∗ p < 0.05; ∗∗ p < 0.01; ∗∗∗ p < 0.001; ANOVA and Bonferroni post-test.
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TP53 mut/mut-like AMLs are associated with increased susceptibility to ferroptosis-induced cell death (A) Violin plots displaying the ES for the REACTOME_ACTIVATION_GENE_EXPRESSION_BY_SREBF_SREBP (left side) and the gene expression levels (transcripts per million, TPM) for the SREBP-related genes ( SCD and HMGCS1 ) for AML patients included in the TCGA cohort ( n = 173). Patients were categorized according to the TP53 mutational status into TP53 wt, TP53 mut-like, and TP53 mut. (B and C) Relative mRNA expression levels of Δ Np73 , CEBPA/CEBPB , and its related targets at baseline and upon dipyridamole (DP) treatment (10 μM) in MOLM13 ΔNp73-OE/EV (pMEG) cells (48 h) (B) and at baseline in MOLM13-KO/Scr control cells (C) ( n = 4). (D) Drug-induced apoptosis in MOLM13 and MV4-11 cells (ΔNp73-OE and EV control) treated with ferroptosis-related <t>drugs</t> <t>KPT-9274</t> (NAMPT inhibitor ) and DP alone or in combination with VEN (concentrations indicated in the plots, 72 h) detected by flow cytometry. (E and F) Drug-induced apoptosis (E) and total ROS levels (F) in MOLM13 cells (ΔNp73-OE and EV control) treated with the GPX4 inhibitors RSL3 and ML210 (concentrations indicated in the plots, 72 h) detected by flow cytometry. (G) Viable cell counts of MOLM13 cells (ΔNp73-OE and EV control) treated with the SCD inhibitor MK-8245 (concentrations indicated in the plots, 72 h) detected by flow cytometry ( n = 4). Data are reported as mean ± SEM for (B)–(G). The p values and cell types are indicated in the graphs; ∗ p < 0.05; ∗∗ p < 0.01; ∗∗∗ p < 0.001; ANOVA and Bonferroni post-test.
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TP53 mut/mut-like AMLs are associated with increased susceptibility to ferroptosis-induced cell death (A) Violin plots displaying the ES for the REACTOME_ACTIVATION_GENE_EXPRESSION_BY_SREBF_SREBP (left side) and the gene expression levels (transcripts per million, TPM) for the SREBP-related genes ( SCD and HMGCS1 ) for AML patients included in the TCGA cohort ( n = 173). Patients were categorized according to the TP53 mutational status into TP53 wt, TP53 mut-like, and TP53 mut. (B and C) Relative mRNA expression levels of Δ Np73 , CEBPA/CEBPB , and its related targets at baseline and upon dipyridamole (DP) treatment (10 μM) in MOLM13 ΔNp73-OE/EV (pMEG) cells (48 h) (B) and at baseline in MOLM13-KO/Scr control cells (C) ( n = 4). (D) Drug-induced apoptosis in MOLM13 and MV4-11 cells (ΔNp73-OE and EV control) treated with ferroptosis-related <t>drugs</t> <t>KPT-9274</t> (NAMPT inhibitor ) and DP alone or in combination with VEN (concentrations indicated in the plots, 72 h) detected by flow cytometry. (E and F) Drug-induced apoptosis (E) and total ROS levels (F) in MOLM13 cells (ΔNp73-OE and EV control) treated with the GPX4 inhibitors RSL3 and ML210 (concentrations indicated in the plots, 72 h) detected by flow cytometry. (G) Viable cell counts of MOLM13 cells (ΔNp73-OE and EV control) treated with the SCD inhibitor MK-8245 (concentrations indicated in the plots, 72 h) detected by flow cytometry ( n = 4). Data are reported as mean ± SEM for (B)–(G). The p values and cell types are indicated in the graphs; ∗ p < 0.05; ∗∗ p < 0.01; ∗∗∗ p < 0.001; ANOVA and Bonferroni post-test.
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TP53 mut/mut-like AMLs are associated with increased susceptibility to ferroptosis-induced cell death (A) Violin plots displaying the ES for the REACTOME_ACTIVATION_GENE_EXPRESSION_BY_SREBF_SREBP (left side) and the gene expression levels (transcripts per million, TPM) for the SREBP-related genes ( SCD and HMGCS1 ) for AML patients included in the TCGA cohort ( n = 173). Patients were categorized according to the TP53 mutational status into TP53 wt, TP53 mut-like, and TP53 mut. (B and C) Relative mRNA expression levels of Δ Np73 , CEBPA/CEBPB , and its related targets at baseline and upon dipyridamole (DP) treatment (10 μM) in MOLM13 ΔNp73-OE/EV (pMEG) cells (48 h) (B) and at baseline in MOLM13-KO/Scr control cells (C) ( n = 4). (D) Drug-induced apoptosis in MOLM13 and MV4-11 cells (ΔNp73-OE and EV control) treated with ferroptosis-related <t>drugs</t> <t>KPT-9274</t> (NAMPT inhibitor ) and DP alone or in combination with VEN (concentrations indicated in the plots, 72 h) detected by flow cytometry. (E and F) Drug-induced apoptosis (E) and total ROS levels (F) in MOLM13 cells (ΔNp73-OE and EV control) treated with the GPX4 inhibitors RSL3 and ML210 (concentrations indicated in the plots, 72 h) detected by flow cytometry. (G) Viable cell counts of MOLM13 cells (ΔNp73-OE and EV control) treated with the SCD inhibitor MK-8245 (concentrations indicated in the plots, 72 h) detected by flow cytometry ( n = 4). Data are reported as mean ± SEM for (B)–(G). The p values and cell types are indicated in the graphs; ∗ p < 0.05; ∗∗ p < 0.01; ∗∗∗ p < 0.001; ANOVA and Bonferroni post-test.
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TP53 mut/mut-like AMLs are associated with increased susceptibility to ferroptosis-induced cell death (A) Violin plots displaying the ES for the REACTOME_ACTIVATION_GENE_EXPRESSION_BY_SREBF_SREBP (left side) and the gene expression levels (transcripts per million, TPM) for the SREBP-related genes ( SCD and HMGCS1 ) for AML patients included in the TCGA cohort ( n = 173). Patients were categorized according to the TP53 mutational status into TP53 wt, TP53 mut-like, and TP53 mut. (B and C) Relative mRNA expression levels of Δ Np73 , CEBPA/CEBPB , and its related targets at baseline and upon dipyridamole (DP) treatment (10 μM) in MOLM13 ΔNp73-OE/EV (pMEG) cells (48 h) (B) and at baseline in MOLM13-KO/Scr control cells (C) ( n = 4). (D) Drug-induced apoptosis in MOLM13 and MV4-11 cells (ΔNp73-OE and EV control) treated with ferroptosis-related <t>drugs</t> <t>KPT-9274</t> (NAMPT inhibitor ) and DP alone or in combination with VEN (concentrations indicated in the plots, 72 h) detected by flow cytometry. (E and F) Drug-induced apoptosis (E) and total ROS levels (F) in MOLM13 cells (ΔNp73-OE and EV control) treated with the GPX4 inhibitors RSL3 and ML210 (concentrations indicated in the plots, 72 h) detected by flow cytometry. (G) Viable cell counts of MOLM13 cells (ΔNp73-OE and EV control) treated with the SCD inhibitor MK-8245 (concentrations indicated in the plots, 72 h) detected by flow cytometry ( n = 4). Data are reported as mean ± SEM for (B)–(G). The p values and cell types are indicated in the graphs; ∗ p < 0.05; ∗∗ p < 0.01; ∗∗∗ p < 0.001; ANOVA and Bonferroni post-test.
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Image Search Results


TP53 mut/mut-like AMLs are associated with increased susceptibility to ferroptosis-induced cell death (A) Violin plots displaying the ES for the REACTOME_ACTIVATION_GENE_EXPRESSION_BY_SREBF_SREBP (left side) and the gene expression levels (transcripts per million, TPM) for the SREBP-related genes ( SCD and HMGCS1 ) for AML patients included in the TCGA cohort ( n = 173). Patients were categorized according to the TP53 mutational status into TP53 wt, TP53 mut-like, and TP53 mut. (B and C) Relative mRNA expression levels of Δ Np73 , CEBPA/CEBPB , and its related targets at baseline and upon dipyridamole (DP) treatment (10 μM) in MOLM13 ΔNp73-OE/EV (pMEG) cells (48 h) (B) and at baseline in MOLM13-KO/Scr control cells (C) ( n = 4). (D) Drug-induced apoptosis in MOLM13 and MV4-11 cells (ΔNp73-OE and EV control) treated with ferroptosis-related drugs KPT-9274 (NAMPT inhibitor ) and DP alone or in combination with VEN (concentrations indicated in the plots, 72 h) detected by flow cytometry. (E and F) Drug-induced apoptosis (E) and total ROS levels (F) in MOLM13 cells (ΔNp73-OE and EV control) treated with the GPX4 inhibitors RSL3 and ML210 (concentrations indicated in the plots, 72 h) detected by flow cytometry. (G) Viable cell counts of MOLM13 cells (ΔNp73-OE and EV control) treated with the SCD inhibitor MK-8245 (concentrations indicated in the plots, 72 h) detected by flow cytometry ( n = 4). Data are reported as mean ± SEM for (B)–(G). The p values and cell types are indicated in the graphs; ∗ p < 0.05; ∗∗ p < 0.01; ∗∗∗ p < 0.001; ANOVA and Bonferroni post-test.

Journal: Cell Reports Medicine

Article Title: ΔNp73 isoform defines a TP53 -mutant-like poor-risk subgroup of acute myeloid leukemia

doi: 10.1016/j.xcrm.2025.102540

Figure Lengend Snippet: TP53 mut/mut-like AMLs are associated with increased susceptibility to ferroptosis-induced cell death (A) Violin plots displaying the ES for the REACTOME_ACTIVATION_GENE_EXPRESSION_BY_SREBF_SREBP (left side) and the gene expression levels (transcripts per million, TPM) for the SREBP-related genes ( SCD and HMGCS1 ) for AML patients included in the TCGA cohort ( n = 173). Patients were categorized according to the TP53 mutational status into TP53 wt, TP53 mut-like, and TP53 mut. (B and C) Relative mRNA expression levels of Δ Np73 , CEBPA/CEBPB , and its related targets at baseline and upon dipyridamole (DP) treatment (10 μM) in MOLM13 ΔNp73-OE/EV (pMEG) cells (48 h) (B) and at baseline in MOLM13-KO/Scr control cells (C) ( n = 4). (D) Drug-induced apoptosis in MOLM13 and MV4-11 cells (ΔNp73-OE and EV control) treated with ferroptosis-related drugs KPT-9274 (NAMPT inhibitor ) and DP alone or in combination with VEN (concentrations indicated in the plots, 72 h) detected by flow cytometry. (E and F) Drug-induced apoptosis (E) and total ROS levels (F) in MOLM13 cells (ΔNp73-OE and EV control) treated with the GPX4 inhibitors RSL3 and ML210 (concentrations indicated in the plots, 72 h) detected by flow cytometry. (G) Viable cell counts of MOLM13 cells (ΔNp73-OE and EV control) treated with the SCD inhibitor MK-8245 (concentrations indicated in the plots, 72 h) detected by flow cytometry ( n = 4). Data are reported as mean ± SEM for (B)–(G). The p values and cell types are indicated in the graphs; ∗ p < 0.05; ∗∗ p < 0.01; ∗∗∗ p < 0.001; ANOVA and Bonferroni post-test.

Article Snippet: KPT-9274 (ATG-019) , Selleckchem , S8444.

Techniques: Activation Assay, Gene Expression, Expressing, Control, Flow Cytometry