Academic Journal
Leukemia / Next-generation sequencing identifies major DNA methylation changes during progression of Ph+ chronic myeloid leukemia
العنوان: | Leukemia / Next-generation sequencing identifies major DNA methylation changes during progression of Ph+ chronic myeloid leukemia |
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المؤلفون: | Zöchbauer-Müller, S., Heller, G., Topakian, T., Altenberger, C., Cerny-Reiterer, S., Herndlhofer, S., Ziegler, B., Datlinger, P., Byrgazov, K., Bock, C., Mannhalter, C., Hörmann, G., Sperr, W.R., Lion, T., Zielinski, C.C., Valent, P. |
بيانات النشر: | Springer Nature |
سنة النشر: | 2016 |
المجموعة: | MedUni Vienna ePub (Medzinische Universität Wien) |
مصطلحات موضوعية: | Chronic myeloid leukaemia, DNA methylation, Medical research, Myeloproliferative disease, Next-generation sequencing, Translational research |
جغرافية الموضوع: | UMW:14557, UMW:20829, UMW:18376, UMW:14638, UMW:14581, UMW:20280 |
الوصف: | 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. |
نوع الوثيقة: | article in journal/newspaper |
وصف الملف: | text/html |
اللغة: | English |
تدمد: | 1476-5551 |
Relation: | vignette : https://repositorium.meduniwien.ac.at/titlepage/urn/urn:nbn:at:at-ubmuw:3-25920/128; urn:nbn:at:at-ubmuw:3-25920; https://resolver.obvsg.at/urn:nbn:at:at-ubmuw:3-25920; local:99145536887603331; system:AC15690911 |
DOI: | 10.1038/leu.2016.143 |
الاتاحة: | https://resolver.obvsg.at/urn:nbn:at:at-ubmuw:3-25920 https://doi.org/10.1038/leu.2016.143 https://repositorium.meduniwien.ac.at/doi/10.1038/leu.2016.143 |
Rights: | cc-by-nc-nd_4 |
رقم الانضمام: | edsbas.25E0F901 |
قاعدة البيانات: | BASE |
تدمد: | 14765551 |
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DOI: | 10.1038/leu.2016.143 |