دورية أكاديمية
Silencing of GATA3 defines a novel stem cell-like subgroup of ETP-ALL
| العنوان: | Silencing of GATA3 defines a novel stem cell-like subgroup of ETP-ALL |
|---|---|
| المؤلفون: | L. Fransecky, M. Neumann, S. Heesch, C. Schlee, J. Ortiz-Tanchez, S. Heller, M. Mossner, S. Schwartz, L. H. Mochmann, K. Isaakidis, L. Bastian, U. R. Kees, T. Herold, K. Spiekermann, N. Gökbuget, C. D. Baldus |
| المصدر: | Journal of Hematology & Oncology, Vol 9, Iss 1, Pp 1-12 (2016) |
| بيانات النشر: | BMC, 2016. |
| سنة النشر: | 2016 |
| المجموعة: | LCC:Diseases of the blood and blood-forming organs LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| مصطلحات موضوعية: | GATA3, ETP-ALL, PER-117, Decitabine, Diseases of the blood and blood-forming organs, RC633-647.5, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| الوصف: | Abstract Background GATA3 is pivotal for the development of T lymphocytes. While its effects in later stages of T cell differentiation are well recognized, the role of GATA3 in the generation of early T cell precursors (ETP) has only recently been explored. As aberrant GATA3 mRNA expression has been linked to cancerogenesis, we investigated the role of GATA3 in early T cell precursor acute lymphoblastic leukemia (ETP-ALL). Methods We analyzed GATA3 mRNA expression by RT-PCR (n = 182) in adult patients with T-ALL. Of these, we identified 70 of 182 patients with ETP-ALL by immunophenotyping. DNA methylation was assessed genome wide (Illumina Infinium® HumanMethylation450 BeadChip platform) in 12 patients and GATA3-specifically by pyrosequencing in 70 patients with ETP-ALL. The mutational landscape of ETP-ALL with respect to GATA3 expression was investigated in 18 patients and validated by Sanger sequencing in 65 patients with ETP-ALL. Gene expression profiles (Affymetrix Human genome U133 Plus 2.0) of an independent cohort of adult T-ALL (n = 83) were used to identify ETP-ALL and investigate GATA3low and GATA3high expressing T-ALL patients. In addition, the ETP-ALL cell line PER-117 was investigated for cytotoxicity, apoptosis, GATA3 mRNA expression, DNA methylation, and global gene expression before and after treatment with decitabine. Results In our cohort of 70 ETP-ALL patients, 33 % (23/70) lacked GATA3 expression and were thus defined as GATA3low. DNA methylation analysis revealed a high degree of GATA3 CpG island methylation in GATA3low compared with GATA3high ETP-ALL patients (mean 46 vs. 21 %, p |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1756-8722 |
| Relation: | http://link.springer.com/article/10.1186/s13045-016-0324-8; https://doaj.org/toc/1756-8722 |
| DOI: | 10.1186/s13045-016-0324-8 |
| URL الوصول: | https://doaj.org/article/4c6c66b24eb547a482695c7814df8700 |
| رقم الأكسشن: | edsdoj.4c6c66b24eb547a482695c7814df8700 |
| قاعدة البيانات: | Directory of Open Access Journals |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 17568722 |
|---|---|
| DOI: | 10.1186/s13045-016-0324-8 |