DAA-7PLC related GOApoptosis related GO-40-30IDH2WTDMSOvitamin D receptor signaling pathwaynegave regulaon of mitochondrial depolarizaonposive regulaon of histone deacetylase acvitytyrosine phosphorylaon of Stat3 proteinnegave regulaon of reacve oxygen species metabolic processnegave regulaon of extrinsic apoptoc signaling pathway in absence of ligandlipoprotein metabolic processsphingolipid biosynthec processcell proliferaon0IDH2mutDMSO5.9217.1posive regulaon of apoptoc processposive regulaon of GTPase acvityposive regulaon of cytosolic calcium ion concentraonregulaon of Rho protein signal transduconregulaon of GTPase acvityregulaon of G-protein coupled receptor protein signaling pathwaycAMP-mediated signalingcAMP biosynthec processposive regulaon of extrinsic apoptoc signaling pathway via death domain receptorsblood coagulaon, intrinsic pathwayphosphadylinositol metabolic processposive regulaon of blood coagulaonposive regulaon of plateletacvaon10206.649.88Annexin V3040IDH2mutmIDH2i5.598.92図4 IDH2遺伝子変異TF-1細胞のアポトーシス解析GO analysis: IDH2 WT vs IDH2 mut up and down GOs in IDH2 mut-20-10Fold enrichment図5 IDH2遺伝子変異TF-1細胞のRNAシークエンス解析GO解析の結果を示す。おける脂質代謝適応を是正する薬剤の併用による薬剤耐性克服の可能性を検討した。我々はアラキドン酸代謝に注目し、アラキドン酸をプロスタグランジンおよびロイコトリエンに代謝する酵素であるCOX2、5-LOXの特異的阻害剤を変異IDH2阻害剤と併用したところ、これらの併用により細胞128
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