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Figure 7. Differential methylation profile of KRAS-wildtype and KRAS-mutated chronic myelomonocytic leukemia clones. (A) Hypermethylated regions detected by enhanced reduced representation bisulfite sequencing in KRAS wildtype (A1, A2, A4) compared to KRAS mutated (A3, A5) chronic myelomonocytic leukemia (CMML)- derived induced pluripotent stem cells (iPSC). Arrows, percentage of methylation required to be considered as a differentially methylated region (DMR). Red dots, tiles that fulfill the criteria [absolute methylation difference ≥40% and false discovery rate (FDR) <5%]. (B) Heatmap of DMR based on the Euclidean distance matrix. Red, hypomethylation; blue, hypermethylation; (C) Repartition of DMR that are hypo- or hyper-methylated in KRAS wildtype compared to KRAS(G12D) clones. Asterisk, significance according to the binomial test (P<0.001). (D) Gene ontology of DMR methylated on KRAS(G12D) clones. Bar chart: processes related to hematopoiesis with a FDR <0.1. X-axis, -log10 of the FDR.
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