Dissecting the role of aberrant DNA methylation in human leukaemia

Giovanni Amabile, Annalisa Di Ruscio, Fabian Müller, Robert S. Welner, Henry Yang, Alexander K. Ebralidze, Hong Zhang, Elena Levantini, Lihua Qi, Giovanni Martinelli, Thijn Brummelkamp, Michelle M. Le Beau, Maria Figueroa, Christoph Bock, Daniel G. Tenen

Research output: Contribution to journalArticle

32 Citations (Scopus)

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.

Original languageEnglish (US)
Article number7091
JournalNature Communications
Volume6
DOIs
StatePublished - May 22 2015
Externally publishedYes

Fingerprint

methylation
leukemias
DNA Methylation
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia
deoxyribonucleic acid
Oncogene Fusion
progressions
Myeloproliferative Disorders
Genetic Translocation
Myeloid Cells
oncogenes
Epigenomics
Protein-Tyrosine Kinases
Disease Progression
tyrosine
abnormalities
Fusion reactions
Clone Cells
lesions

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Amabile, G., Di Ruscio, A., Müller, F., Welner, R. S., Yang, H., Ebralidze, A. K., ... Tenen, D. G. (2015). Dissecting the role of aberrant DNA methylation in human leukaemia. Nature Communications, 6, [7091]. https://doi.org/10.1038/ncomms8091

Dissecting the role of aberrant DNA methylation in human leukaemia. / Amabile, Giovanni; Di Ruscio, Annalisa; Müller, Fabian; Welner, Robert S.; Yang, Henry; Ebralidze, Alexander K.; Zhang, Hong; Levantini, Elena; Qi, Lihua; Martinelli, Giovanni; Brummelkamp, Thijn; Le Beau, Michelle M.; Figueroa, Maria; Bock, Christoph; Tenen, Daniel G.

In: Nature Communications, Vol. 6, 7091, 22.05.2015.

Research output: Contribution to journalArticle

Amabile, G, Di Ruscio, A, Müller, F, Welner, RS, Yang, H, Ebralidze, AK, Zhang, H, Levantini, E, Qi, L, Martinelli, G, Brummelkamp, T, Le Beau, MM, Figueroa, M, Bock, C & Tenen, DG 2015, 'Dissecting the role of aberrant DNA methylation in human leukaemia', Nature Communications, vol. 6, 7091. https://doi.org/10.1038/ncomms8091
Amabile G, Di Ruscio A, Müller F, Welner RS, Yang H, Ebralidze AK et al. Dissecting the role of aberrant DNA methylation in human leukaemia. Nature Communications. 2015 May 22;6. 7091. https://doi.org/10.1038/ncomms8091
Amabile, Giovanni ; Di Ruscio, Annalisa ; Müller, Fabian ; Welner, Robert S. ; Yang, Henry ; Ebralidze, Alexander K. ; Zhang, Hong ; Levantini, Elena ; Qi, Lihua ; Martinelli, Giovanni ; Brummelkamp, Thijn ; Le Beau, Michelle M. ; Figueroa, Maria ; Bock, Christoph ; Tenen, Daniel G. / Dissecting the role of aberrant DNA methylation in human leukaemia. In: Nature Communications. 2015 ; Vol. 6.
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