Amabile, GiovanniDi Ruscio, AnnalisaMüller, FabianWelner, Robert SYang, HenryEbralidze, AlexanderZhang, HongLevantini, ElenaQi, LihuaMartinelli, GiovanniBrummelkamp, ThijnLe Beau, Michelle MFigueroa, Maria EBock, ChristophTenen, Daniel2015-12-042015Amabile, G., A. Di Ruscio, F. Müller, R. S. Welner, H. Yang, A. K. Ebralidze, H. Zhang, et al. 2015. “Dissecting the role of aberrant DNA methylation in human leukemia.” Nature communications 6 (1): 7091. doi:10.1038/ncomms8091. http://dx.doi.org/10.1038/ncomms8091.2041-1723http://nrs.harvard.edu/urn-3:HUL.InstRepos:23845161Chronic Myeloid Leukemia (CML) is a myeloproliferative disorder characterized by the genetic translocation t(9;22)(q34;q11.2) encoding for the BCR-ABL fusion oncogene. However, many molecular mechanisms of the disease progression still remain poorly understood. A growing body of evidence suggests that epigenetic abnormalities are involved in tyrosine kinase resistance in CML, leading to leukemic clone escape and disease propagation. Here we show that, by applying cellular reprogramming to primary CML cells, aberrant DNA methylation contributes to the disease evolution. Importantly, using a BCR-ABL inducible murine model, we demonstrate that a single oncogenic lesion triggers DNA methylation changes which in turn act as a precipitating event in leukemia progression.en-USJournal Article2015-12-0410.1038/ncomms8091