Supplementary Material from Inactivation of Receptor Tyrosine Kinases Reverts Aberrant DNA Methylation in Acute Myeloid Leukemia

Abstract

<p>Supplementary Methods, Figures and References Supplementary Figure 1. Tyrosine kinases are positive regulators of DNMT-dependent DNA methylation in leukemia cells. Supplementary Figure 2. Nilotinib treatment inhibits KIT and FLT3 kinase signaling. Supplementary Figure 3. Treatment with RTK inhibitors decreases DNMT1 expression in vitro and in vivo. Supplementary Figure 4. The potential biochemical link between an RTK and DNMT1. Supplementary Figure 5. Nilotinib treatment induces global and gene specific DNA methylation through the Sp1-DNMT1 axis. Supplementary Figure 6. RTK dysfunction reactivates cyclin-dependent kinase inhibitors Supplementary Figure 7. DNMT1-dependent DNA methylation is increased in cells resistant to nilotinib. Supplementary Figure 8. Sp1 overexpression reduces the antileukemia activity of nilotinib. Supplementary Figure 9. Exposure to nilotinib leads to changes in pro- and anti-apoptotic proteins. Supplementary Figure 10. Nilotinib treatment displays no obvious changes in cell cycle. Supplementary Figure 11. Velcade or decitabine sensitizes AML cells to nilotinib treatment. Supplementary Figure 12. Nilotinib exposure induces cell apoptosis through modulation of DNA methylation in the C1498 mouse AML cell line. Supplementary Figure 13. Exposure of AML patient primary cells to nilotinib suppresses oncogene expression and promotes cell apoptosis. Supplementary Figure 14. The anti-leukemia activities of imatinib involve DNA methylation-associated pathways. Supplementary Table. Primer/probe sequences used in the experiments</p>