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. 2024 Nov 15;14(1):201.
doi: 10.1038/s41408-024-01188-3.

Impact of TP53 mutation on genetic and cellular hierarchy profile in complex karyotype AML/MDS with increased blasts

Jinha Hwang  1 , Ha Nui Kim  1 , Jung Ah Kwon  1 , Soo-Young Yoon  1 , Min Ji Jeon  2 , Eun Sang Yu  2 , Dae Sik Kim  2 , Chul Won Choi  2 , Jung Yoon  3
Affiliations

Impact of TP53 mutation on genetic and cellular hierarchy profile in complex karyotype AML/MDS with increased blasts

Jinha Hwang et al. Blood Cancer J. .
No abstract available

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Conflict of interest statement

Competing interests The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Comparative analysis of cell cycle-related gene set enrichment scores and the correlation between cell cycle-related pathway and drug response.
A The scaled enrichment scores from single-sample gene set enrichment analysis (ssGSEA) for three cell cycle-related hallmark gene sets (“HALLMARK_G2M_CHECKPOINT,” “HALLMARK_E2F_TARGETS,” and “HALLMARK_MITOTIC_SPINDLE”) were compared across three groups: non-CK, TP53mut CK and TP53wt CK. Each row represents a different cohort, and each column represents a different gene set. B Drug sensitivity of the non-CK, TP53wt CK, and TP53mut CK groups to elesclomol, JAK inhibitors (ruxolitinib, S1312, and AZD1480), and the STAT3 inhibitor (S31-201). Significance was assessed using the Mann–Whitney test. C Scatter plots showing the correlation between the enrichment score of the “HALLMARK_MITOTIC_SPINDLE” gene set and the AUC for three drugs: (left) cytarabine, (middle) sorafenib, and (right) elesclomol.
Fig. 2
Fig. 2. Cellular hierarchy composition and its association with drug response, cell cycle related gene set enrichment score, and patient survival.
A Distribution of cellular hierarchy composition (GMP, Intermediate, Mature, and Primitive) across non-CK, TP53wt CK, and TP53mut CK groups. B Pearson correlation between the proportion of each cell type and drug sensitivity (-AUC) in the BeatAML cohort, with colors representing the direction of the correlation. Only significant correlations (P < 0.05) are depicted. C Comparison of AUC values for elesclomol and D enrichment scores of three cell cycle-related gene sets between primitive and other cell types in the TP53mut CK group. Detailed cell types within the ‘Others’ category is shown for the hall mark mitotic spindle gene set. E Overall survival outcomes of AML hierarchy subtypes in the TP53mut CK group. Differences in survival outcomes between the subtypes were assessed using the log-rank test.
See this image and copyright information in PMC

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