Fig. 4: DNA methylation changes after IDHi. | Nature Communications

Fig. 4: DNA methylation changes after IDHi.

From: Leukemia stemness and co-occurring mutations drive resistance to IDH inhibitors in acute myeloid leukemia

Fig. 4

A Longitudinal trend of methylation level at baseline (BL) and posttreatment (POST) for all, cluster 1 and cluster 2 patients. Responders and nonresponders are color coded. Two-sided Student’s t test was performed. B Box plot showing maximum reduction of plasma 2HG levels after IDHi treatment (%) in cluster 1 (N = 17) and cluster 2 (N = 10) patients, as well as responders (N = 13) and nonresponders (N = 14). Box plot shows the minimum, first quartile (Q1), median, third quartile (Q3), and maximum. Two-sided Student’s t test was performed. C Scatterplot showing correlation of the longitudinal methylation changes between cluster 1 and cluster 2 patients. Each dot represents a CpG probe and was colored based on its significance in the longitudinal differentially methylation test in either cluster 1 or cluster 2 patients. The X-axis represents the differential methylation level between BL and POST samples (i.e., beta value at BL minus beta value at POST) in cluster 1 patients and the Y-axis represents the differential methylation level between BL and POST samples in cluster 2 patients. D Scatterplot showing correlation of the intercluster methylation differences between BL and POST time points. Each dot represents a CpG probe and was colored based on its significance in the intercluster differentially methylation test at either BL or POST time points. The X-axis represents the differential methylation level between cluster 1 and cluster 2 in BL samples (i.e., beta value of cluster 1 minus cluster 2) and the Y-axis represents the differential methylation level between cluster 1 and cluster 2 in POST samples. E Venn diagram showing the overlapped DMPs between cluster 1 and cluster 2 at baseline (BL) and posttreatment (POST). Among 2621 DMPs hypermethylated in cluster 2, 2156 overlapped between BL and POST, suggesting that most of the hypermethylated DMPs in cluster 2 were the same before and after treatment. F Scatterplot showing correlation of the longitudinal methylation changes between responders and nonresponders. Each dot represents a CpG probe and was colored based on its significance in the longitudinal differentially methylation test in either responders or nonresponders. The X-axis represents the differential methylation level between baseline and response samples in responders (i.e., beta value at BL minus beta value at POST) and the Y-axis represents the differential methylation level between baseline and non-response samples in nonresponders. G GSEA analysis comparing gene expression of posttreatment samples between cluster 1 and cluster 2 showed that LSC genes are still upregulated in cluster 2 posttreatment. Source data are provided as Source data files.

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