Dissecting the role of aberrant DNA methylation in human leukaemia.
Giovanni AmabileAnnalisa Di RuscioFabian MüllerRobert S WelnerHenry YangAlexander K EbralidzeHong ZhangElena LevantiniLihua QiGiovanni MartinelliThijn BrummelkampMichelle M Le BeauMaria E FigueroaChristoph BockDaniel G TenenPublished in: Nature communications (2015)
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.
Keyphrases
- dna methylation
- tyrosine kinase
- chronic myeloid leukemia
- genome wide
- epidermal growth factor receptor
- gene expression
- induced apoptosis
- copy number
- endothelial cells
- bone marrow
- acute lymphoblastic leukemia
- dendritic cells
- transcription factor
- acute myeloid leukemia
- living cells
- endoplasmic reticulum stress
- fluorescent probe
- immune response
- oxidative stress
- induced pluripotent stem cells
- signaling pathway