@article{oai:asahikawa-med.repo.nii.ac.jp:00005795, author = {山本, 昌代 and 田中, 宏樹 and 土岐, 康通 and 畑山, 真弓 and 伊藤, 巧 and Addo, Lynda and 進藤, 基博 and 佐々木, 勝則 and 生田, 克哉 and 大竹, 孝明 and 藤谷, 幹浩 and 鳥本, 悦宏 and 高後, 裕}, issue = {4}, journal = {International Journal of Hematology}, month = {Oct}, note = {PMID:27380194, Iron overload remains a concern in myelodysplastic syndrome (MDS) patients. Iron chelation therapy (ICT) thus plays an integral role in the management of these patients. Moreover, ICT has been shown to prolong leukemia-free survival in MDS patients; however, the mechanisms responsible for this effect are unclear. Iron is a key molecule for regulating cytosolic aconitase 1 (ACO1). Additionally, the mutation of isocitrate dehydrogenase (IDH), the enzyme downstream of ACO1 in the TCA cycle, is associated with epigenetic abnormalities secondary to 2-hydroxyglutarate (2-HG) and DNA methylation. However, epigenetic abnormalities observed in many MDS patients occur without IDH mutation. We hypothesized that iron itself activates the ACO1-IDH pathway, which may increase 2-HG and DNA methylation, and eventually contribute to leukemogenesis without IDH mutation. Using whole RNA sequencing of bone marrow cells in iron-overloaded mice, we observed that the enzymes, phosphoglucomutase 1, glycogen debranching enzyme, and isocitrate dehydrogenase 1 (Idh1), which are involved in glycogen and glucose metabolism, were increased. Digital PCR further showed that Idh1 and Aco1, enzymes involved in the TCA cycle, were also elevated. Additionally, enzymatic activities of TCA cycle and methylated DNA were increased. Iron chelation reversed these phenomena. In conclusion, iron activation of glucose metabolism causes an increase of 2-HG and DNA methylation., The final publication is available at Springer via http://dx.doi.org/10.1007/s12185-016-2054-7, text, application/pdf}, pages = {491--501}, title = {Iron-induced epigenetic abnormalities of mouse bone marrow through aberrant activation of aconitase and isocitrate dehydrogenase}, volume = {104}, year = {2016}, yomi = {ヤマモト, マサヨ and タナカ, ヒロキ and トキ, ヤスミチ and ハタヤマ, マユミ and イトウ, サトシ and シンドウ, モトヒロ and ササキ, カツノリ and イクタ, カツヤ and オオタケ, タカアキ and フジヤ, ミキヒロ and トリモト, ヨシヒロ and コウゴ, ユタカ} }