Next-generation sequencing identifies major DNA methylation changes during progression of Ph+ chronic myeloid leukemia.
|
| Abstract |
Little is known about the impact of DNA methylation on the evolution/progression of Ph+ chronic myeloid leukemia (CML). We investigated the methylome of CML patients in chronic phase (CP-CML), accelerated phase (AP-CML) and blast crisis (BC-CML) as well as in controls by reduced representation bisulfite sequencing. Although only ~600 differentially methylated CpG sites were identified in samples obtained from CP-CML patients compared with controls, ~6500 differentially methylated CpG sites were found in samples from BC-CML patients. In the majority of affected CpG sites, methylation was increased. In CP-CML patients who progressed to AP-CML/BC-CML, we identified up to 897 genes that were methylated at the time of progression but not at the time of diagnosis. Using RNA-sequencing, we observed downregulated expression of many of these genes in BC-CML compared with CP-CML samples. Several of them are well-known tumor-suppressor genes or regulators of cell proliferation, and gene re-expression was observed by the use of epigenetic active drugs. Together, our results demonstrate that CpG site methylation clearly increases during CML progression and that it may provide a useful basis for revealing new targets of therapy in advanced CML.
|
|---|---|
| Authors | G Heller, T Topakian, C Altenberger, S Cerny-Reiterer, S Herndlhofer, B Ziegler, P Datlinger, K Byrgazov, C Bock, C Mannhalter, G Hörmann, W R Sperr, T Lion, C C Zielinski, P Valent, S Zöchbauer-Müller |
| Journal | Leukemia (Leukemia) Vol. 30 Issue 9 Pg. 1861-8 (09 2016) ISSN: 1476-5551 [Electronic] England |
| PMID | 27211271 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Topics |
|
Join CureHunter, for free Research Interface BASIC access!
Realize the full power of the drug-disease research graph!