Chronic myelogenous leukemia (CML) is a malignant clonal disease of hematopoietic stem cells. Researches have exhibited that the progression of CML is related to histone modifications. Here, we perform the systematic analyses of H3K36me3 patterns and gene expression level changes. We observe that the genes with higher gene-body H3K36me3 levels in normal cells show fewer expression changes during leukemogenesis, while the genes with lower gene-body H3K36me3 levels in normal cells yield obvious expression changes during leukemogenesis (ρ=-0.98, P=9.30×10^-8). These findings are conserved in human lung/breast cancers and mouse CML, regardless of gene expression levels and gene lengths. Regulatory element analysis and Random Forest regression display that Hoxd13, Rara, Scl, Smad3, Smad4 and Tgif1 induce the up-regulation of genes with lower H3K36me3 levels (ρ=0.97, P=2.35×10^-56). Enrichment analysis shows that the differentially expressed genes with lower H3K36me3 levels are involved in leukemia-related pathways, such as leukocyte migration and regulation of leukocyte activation. Finally, six driver genes (Tp53, Wt1, Dnmt3a, Cacna1b, Phactr1 and Gbp4) with lower H3K36me3 levels are identified. Our analyses indicate that lower gene-body H3K36me3 levels may serve as a biomarker for the progression of CML.

慢性粒细胞白血病（CML）是一种造血干细胞恶性克隆性疾病。研究表明，CML 的进展与组蛋白修饰有关。在这里，我们对 H3K36me3 模式和基因表达水平变化进行系统分析。我们观察到正常细胞中基因体H3K36me3水平较高的基因在白血病发生过程中表现出较少的表达变化，而正常细胞中基因体H3K36me3水平较低的基因在白血病发生过程中表现出明显的表达变化（ρ=-0.98，P=9.30 ×10 ^-8）。无论基因表达水平和基因长度如何，这些发现在人肺癌/乳腺癌和小鼠 CML 中都是保守的。调控元素分析和随机森林回归显示，Hoxd13、Rara、Scl、Smad3、Smad4 和 Tgif1 诱导 H3K36me3 水平较低的基因上调（ρ=0.97，P=2.35×10 ^-56）。富集分析表明，具有较低H3K36me3水平的差异表达基因参与了白血病相关通路，如白细胞迁移和白细胞活化的调节。最后，六个驱动基因（Tp53、Wt1、Dnmt3a、Cacna1b、Phactr1和Gbp4) 具有较低的 H3K36me3 水平。我们的分析表明，较低的基因体 H3K36me3 水平可以作为 CML 进展的生物标志物。