High expression of ABCG2 induced by EZH2 disruption has pivotal roles in MDS pathogenesis Journal Article
| Authors: | Kawabata, K. C.; Hayashi, Y.; Inoue, D.; Meguro, H.; Sakurai, H.; Fukuyama, T.; Tanaka, Y.; Asada, S.; Fukushima, T.; Nagase, R.; Takeda, R.; Harada, Y.; Kitaura, J.; Goyama, S.; Harada, H.; Aburatani, H.; Kitamura, T. |
| Article Title: | High expression of ABCG2 induced by EZH2 disruption has pivotal roles in MDS pathogenesis |
| Abstract: | Both proto-oncogenic and tumor-suppressive functions have been reported for enhancer of zeste homolog 2 (EZH2). To investigate the effects of its inactivation, a mutant EZH2 lacking its catalytic domain was prepared (EZH2-dSET). In a mouse bone marrow transplant model, EZH2-dSET expression in bone marrow cells induced a myelodysplastic syndrome (MDS)-like disease in transplanted mice. Analysis of these mice identified Abcg2 as a direct target of EZH2. Intriguingly, Abcg2 expression alone induced the same disease in the transplanted mice, where stemness genes were enriched. Interestingly, ABCG2 expression is specifically high in MDS patients. The present results indicate that ABCG2 de-repression induced by EZH2 mutations have crucial roles in MDS pathogenesis. |
| Keywords: | cancer cells; stem-cells; acute myeloid-leukemia; blast crisis; somatic mutations; hematopoietic; polycomb group proteins; myelodysplastic; syndromes; gene ezh2; histone methyltransferase ezh2; h3 lysine 27 |
| Journal Title: | Leukemia |
| Volume: | 32 |
| Issue: | 2 |
| ISSN: | 0887-6924 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2018-02-01 |
| Start Page: | 419 |
| End Page: | 428 |
| Language: | English |
| ACCESSION: | WOS:000424517300019 |
| DOI: | 10.1038/leu.2017.227 |
| PROVIDER: | wos |
| PUBMED: | 28720764 |
| Notes: | Article -- Source: Wos |
