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.

journal_name

Nat Commun

journal_title

Nature communications

authors

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 ME,Bock C,Tenen DG

doi

10.1038/ncomms8091

subject

Has Abstract

pub_date

2015-05-22 00:00:00

pages

7091

issn

2041-1723

pii

ncomms8091

journal_volume

6

pub_type

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