{"id":"hum0384","version":2,"url":"https://humandbs.dbcls.jp/research/hum0384/v2","datePublished":"2025-07-01","versions":[{"version":1,"datePublished":"2024-06-19"},{"version":2,"datePublished":"2025-07-01"}],"title":{"ja":"造血器腫瘍の分子病態の解明と新規治療薬開発の基盤構築","en":"Deciphering molecular mechanisms underlying hematological malignancies and development of novel therapeutic approaches"},"summary":{"aims":{"ja":"造血器腫瘍の腫瘍細胞のゲノム・エピゲノム・遺伝子発現解析を行い、腫瘍特異的な遺伝子・エピゲノム・遺伝子発現異常を明らかにすることで、治療標的になりうるか検討する。具体的には、in vitroでの阻害剤投与による抗腫瘍効果の解析や、腫瘍細胞を免疫不全マウスに移植したxenograftモデルを確立し、治療標的の候補となった分子の阻害剤を投与する事でin vivo治療モデルを構築する。最終的には、造血器腫瘍の新規治療薬開発や予後向上に貢献する事を目指す。","en":"To identify genomic/epigenomic/transcriptomic features dysregulated in hematological malignancies through genomic/epigenetic/transcriptomic analyses of hematological malignant cells. Regarding identified epigenomic abnormalities, we perform further analysis to determine whether they could be good candidates to translate into therapy development. To this end, we will modulate the activity of targets by using their activators and inhibitors in vitro and establish xenograft mouse models of hematological malignancies and manipulate their activity in vivo. Through these studies, we develop new therapeutic agents or modalities that lead to improved patients' prognoses."},"methods":{"ja":"造血器腫瘍の確定診断のため採取した骨髄穿刺液の一部を用いる。Ficoll処理により単核球を抽出し、正常細胞の混入を出来るだけ避けるために、MACSビーズもしくはFACS sorterを用いて腫瘍細胞をsortingする。これらの細胞を用いて、遺伝子変異情報を得るために、主要な変異遺伝子のtarget deep sequencingを行うとともに、RNAシークエンスによる遺伝子発現プロファイル解析、およびクロマチン状態と転写制御ネットワークの解析を行うため ATAC-seq によるオープンクロマチン領域の解析を行う。","en":"A part of bone marrow aspirates (3 ml) obtained to perform a definite diagnosis will be provided for this study. Mononuclear cells are separated by gradient separation using Ficoll, then subjected to magnetic beads separation to purify CD34+ hematopoietic stem and progenitor cells (HSPCs). CD34+ HSPCs are subjected to RNA sequencing, target capture sequencing and ATAC sequencing analyses."},"targets":{"ja":"共同研究機関（都立駒込病院、文京学院大学、千葉大学附属病院）にて収集した急性骨髄芽球性白血病症例ならびに骨髄異形成症候群症例、および Lonza にて購入した正常細胞","en":"acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) specimens were collected at Komagome Hospital and its affiliated city hospitals. Normal cells were purchased from Lonza."},"url":{"ja":null,"en":null}},"listingSummary":{"methods":{"ja":"発現\n配列決定","en":"Expression profiling, Sequencing"},"targets":{"ja":"急性骨髄芽球性白血病：4＋4症例\n骨髄異形成症候群：30症例\n（日本人）\n正常細胞：6検体\n（細胞株）","en":"AML: 4 + 4 cases\nMDS: 30 cases\n(Japanese)\nnormal cell: 6 samples\n(Cell-line)"},"typeOfData":{"ja":"NGS\n（RNA-seq、Target Capture、ATAC-seq）","en":"NGS\n(RNA-seq, Target Capture, ATAC-seq)"}},"releaseNote":{"ja":"急性骨髄芽球性白血病の腫瘍細胞から抽出したDNA/RNAを対象としたRNA sequencingおよびATAC-seq解析データをfastqファイルにて提供する。","en":"DNA/RNA extracted from acute myeloid leukemia (AML) were used for RNA sequencing and ATAC sequencing analyses. Fastq files are provided."},"dataProviders":[{"name":{"ja":"岩間 厚志","en":"Atsushi Iwama"},"organization":{"name":{"ja":"東京大学 医科学研究所 幹細胞治療研究センター 幹細胞分子医学分野","en":"Division of Stem Cell and Molecular Medicine, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo"}}}],"researchProjects":[],"grants":[{"title":{"ja":"MDS病態の分子基盤の解明と新規予後予測システムの構築","en":"Molecular basis of MDS pathogenesis and construction of novel MDS prognostic model"},"agency":{"ja":"科学研究費助成事業 基盤研究（C）","en":"KAKENHI Grant-in-Aid for Scientific Research (C)"},"grantIds":["21K08366"]},{"title":{"ja":"クロマチン特性解析によるMDS分子病態の解明","en":"Elucidation of MDS molecular pathogenesis by chromatin characterization"},"agency":{"ja":"科学研究費助成事業 基盤研究（C）","en":"KAKENHI Grant-in-Aid for Scientific Research (C)"},"grantIds":["24K11554"]}],"relatedPublications":[],"datasets":["JGAD000732","JGAD000851"],"controlledAccessUsers":[]}