剖析异常DNA甲基化在人类白血病中的作用。

Dissecting the role of aberrant DNA methylation in human leukaemia.

作者信息

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 E, Bock Christoph, Tenen Daniel G

机构信息

1] Harvard Medical School, Boston, Massachusetts 02115, USA [2] Harvard Stem Cell Institute, Harvard University, Cambridge, Massachusetts 02138, USA.

Max Plank Institute for Informatics, Saarbrücken 117599, Germany.

出版信息

Nat Commun. 2015 May 22;6:7091. doi: 10.1038/ncomms8091.

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.