Figure 1.
TP53 mutations correlate with an immune-infiltrated TME in TCGA-AML. (A) Heatmap of immune-cell-type–specific scores and biological activity scores in TCGA-AML cases with information on prognostic molecular lesions (n = 118; unsupervised hierarchical clustering; Euclidean distance; complete linkage). ClustVis, an online tool for clustering of multivariate data, was used for data analysis and visualization.47 The optimal number of clusters was defined through silhouette scoring using an open-source machine learning toolkit (Orange3, version 3.25.0). FLT3-ITD, fms-like tyrosine kinase 3 internal tandem duplication; NPM1, nucleophosmin-1. ELN intermediate cases were further subclassified into molecular low-risk cases (NPM1 mutations without FLT3-ITD) and molecular high-risk cases (NPM1 WT with FLT3-ITD).22 (B) Fraction of genome altered in TCGA-AML cases with TP53 mutations (n = 14) and other prognostic molecular lesions (n = 104). Bars denote median values. Data were retrieved through cBioPortal and were compared using the Mann-Whitney U test for unpaired determinations. (C) Box plots showing immune signature scores in TCGA-AML cases with TP53 mutations (n = 14) and other prognostic molecular lesions (n = 19 with NPM1 mutations; n = 22 with RUNX1 mutations; n = 48 with FLT3-ITD without NPM1 mutations; n = 15 with CHIP-defining mutations). Data were compared using the Kruskal-Wallis test for unpaired determinations with Bonferroni’s correction for multiple comparisons. (D) TIS, inflammatory chemokine, IFN-γ, and lymphoid signature scores in TCGA cases with TP53 mutations with (n = 9 cases) or without a CK (n = 13 cases) for whom immune gene signature scores could be computed. Data were compared using the Mann-Whitney U test for unpaired determinations. (E) Expression of FOXP3 and immune checkpoints PD-L1 and TIGIT in TCGA-AML cases with TP53 mutations (n = 14) and other prognostic molecular lesions (n = 104). Bars denote median values. Data were compared using the Mann-Whitney U test for unpaired determinations. ND, not determined.

TP53 mutations correlate with an immune-infiltrated TME in TCGA-AML. (A) Heatmap of immune-cell-type–specific scores and biological activity scores in TCGA-AML cases with information on prognostic molecular lesions (n = 118; unsupervised hierarchical clustering; Euclidean distance; complete linkage). ClustVis, an online tool for clustering of multivariate data, was used for data analysis and visualization.47  The optimal number of clusters was defined through silhouette scoring using an open-source machine learning toolkit (Orange3, version 3.25.0). FLT3-ITD, fms-like tyrosine kinase 3 internal tandem duplication; NPM1, nucleophosmin-1. ELN intermediate cases were further subclassified into molecular low-risk cases (NPM1 mutations without FLT3-ITD) and molecular high-risk cases (NPM1 WT with FLT3-ITD).22  (B) Fraction of genome altered in TCGA-AML cases with TP53 mutations (n = 14) and other prognostic molecular lesions (n = 104). Bars denote median values. Data were retrieved through cBioPortal and were compared using the Mann-Whitney U test for unpaired determinations. (C) Box plots showing immune signature scores in TCGA-AML cases with TP53 mutations (n = 14) and other prognostic molecular lesions (n = 19 with NPM1 mutations; n = 22 with RUNX1 mutations; n = 48 with FLT3-ITD without NPM1 mutations; n = 15 with CHIP-defining mutations). Data were compared using the Kruskal-Wallis test for unpaired determinations with Bonferroni’s correction for multiple comparisons. (D) TIS, inflammatory chemokine, IFN-γ, and lymphoid signature scores in TCGA cases with TP53 mutations with (n = 9 cases) or without a CK (n = 13 cases) for whom immune gene signature scores could be computed. Data were compared using the Mann-Whitney U test for unpaired determinations. (E) Expression of FOXP3 and immune checkpoints PD-L1 and TIGIT in TCGA-AML cases with TP53 mutations (n = 14) and other prognostic molecular lesions (n = 104). Bars denote median values. Data were compared using the Mann-Whitney U test for unpaired determinations. ND, not determined.

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