title: Dissecting the role of aberrant DNA methylation in human leukaemia.
abstract: Chronic myeloid leukaemia (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 the epigenetic abnormalities are involved in tyrosine kinase resistance in CML, leading to leukaemic 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 leukaemia progression.
authors.affiliation: 1] Harvard Medical School, Boston, Massachusetts 02115, USA [2] Harvard Stem Cell Institute, Harvard University, Cambridge, Massachusetts 02138, USA.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Amabile
authors.affiliation: 1] Harvard Medical School, Boston, Massachusetts 02115, USA [2] Harvard Stem Cell Institute, Harvard University, Cambridge, Massachusetts 02138, USA.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Di Ruscio
authors.affiliation: Max Plank Institute for Informatics, Saarbrücken 117599, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Müller
authors.affiliation: 1] Harvard Medical School, Boston, Massachusetts 02115, USA [2] Harvard Stem Cell Institute, Harvard University, Cambridge, Massachusetts 02138, USA.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Welner
authors.affiliation: Cancer Science Institute, National University of Singapore, Singapore 66123, Singapore.
authors.forename: Henry
authors.initials: H
authors.lastname: Yang
authors.affiliation: 1] Harvard Medical School, Boston, Massachusetts 02115, USA [2] Harvard Stem Cell Institute, Harvard University, Cambridge, Massachusetts 02138, USA.
authors.forename: Alexander K
authors.initials: AK
authors.lastname: Ebralidze
authors.affiliation: 1] Harvard Medical School, Boston, Massachusetts 02115, USA [2] Harvard Stem Cell Institute, Harvard University, Cambridge, Massachusetts 02138, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: 1] Harvard Medical School, Boston, Massachusetts 02115, USA [2] Harvard Stem Cell Institute, Harvard University, Cambridge, Massachusetts 02138, USA [3] Institute of Biomedical Technologies, National Research Council (CNR), Pisa 56124, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Levantini
authors.affiliation: Cancer Science Institute, National University of Singapore, Singapore 66123, Singapore.
authors.forename: Lihua
authors.initials: L
authors.lastname: Qi
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna 40126, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Martinelli
authors.affiliation: Netherlands Cancer Institute, Amsterdam 1066, The Netherlands.
authors.forename: Thijn
authors.initials: T
authors.lastname: Brummelkamp
authors.affiliation: Section of Hematology/Oncology and the Comprehensive Cancer Center, University of Chicago, Chicago, Illinois 60637, USA.
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Le Beau
authors.affiliation: University of Michigan, Department of Pathology, Ann Arbor, Michigan 48109-2200, USA.
authors.forename: Maria E
authors.initials: ME
authors.lastname: Figueroa
authors.affiliation: 1] Max Plank Institute for Informatics, Saarbrücken 117599, Germany [2] CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna 1090, Austria [3] Department of Laboratory Medicine, Medical University of Vienna, Vienna 1090, Austria.
authors.forename: Christoph
authors.identifier: 0000000160913088
authors.initials: C
authors.lastname: Bock
authors.affiliation: 1] Harvard Medical School, Boston, Massachusetts 02115, USA [2] Harvard Stem Cell Institute, Harvard University, Cambridge, Massachusetts 02138, USA [3] Cancer Science Institute, National University of Singapore, Singapore 66123, Singapore.
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Tenen
mesh_terms: D000818:Animals; D001374:Azacitidine; D002454:Cell Differentiation; D000067470:Cellular Reprogramming Techniques; D019175:DNA Methylation; D016313:Genes, abl; D006801:Humans; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics*; D008822:Mice, Transgenic; D020298:U937 Cells
chemical_list: D001374:Azacitidine