Molecular analysis of bone marrow failure syndrome modeled on donor derived bone marrow failure syndrome

• Project/Area Number: 16K20973
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Hematology; Tumor biology
• Research Institution: National Hospital Organization Nagoya Medical Center
• Principal Investigator: Yasuda Takahiko 独立行政法人国立病院機構(名古屋医療センター臨床研究センター), その他部局等, その他 (20723977)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 骨髄不全症候群 / 造血幹細胞移植 / ドナー由来 / 全エクソン解析 / ドナー由来骨髄不全症候群 / T細胞レパトア解析 / 同種造血幹細胞移植 / ゲノム

Outline of Final Research Achievements

We experienced four patients with bone marrow failure syndrome after allogeneic stem cell transplantation who sustain donor derived hematopoiesis. We aim to clarify a molecular mechanisms for development of bone marrow failure syndrome using specimens of patients of donor derived bone marrow failure syndrome. Whole exome sequencing revealed 5-10 somatic mutation with low allele frequencies in each patients. Low burden of clonal hematopoiesis with somatic mutations might be a characteristics of this complications after allogeneic stem cell transplantation.

Research Products

• [Journal Article] Acute lymphoblastic leukemia of adolescents and young adults: from the viewpoint of physicians (2017)
  • Author(s): 安田 貴彦、早川 文彦
  • Journal Title: 臨床血液 Volume: 58 Issue: 8 Pages: 1031-1037
  • DOI: 10.11406/rinketsu.58.1031
  • Peer Reviewed
• [Journal Article] Integrative analysis of genomic alterations in triple-negative breast cancer in association with homologous recombination deficiency (2017)
  • Author(s): Kawazu Masahito、Kojima Shinya、Ueno Toshihide、Totoki Yasushi、Nakamura Hiromi、Kunita Akiko et.al.
  • Journal Title: PLOS Genetics Volume: 13
  • DOI: 10.1371/journal.pgen.1006853
  • Peer Reviewed
• [Journal Article] PAX5 tyrosine phosphorylation by SYK co-operatively functions with its serine phosphorylation to cancel the PAX5-dependent repression of BLIMP1: A mechanism for antigen-triggered plasma cell differentiation. (2016)
  • Author(s): Inagaki Y, Hayakawa F, Hirano D, Kojima Y, Morishita T, Yasuda T, Naoe T, Kiyoi H
  • Journal Title: Biochem Biophys Res Commun Volume: 475 Pages: 176-181
  • DOI: 10.1016/j.bbrc.2016.05.067
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Recurrent DUX4 fusions in B-cell acute lymphoblastic leukemia of adolescents and young adults. (2016)
  • Author(s): Yasuda T, Tsuzuki S, Kawazu M, Hayakawa F, Kojima S, Ueno T, Imoto N, Kohsaka S, Kunita A, Doi K, Sakura T, Yujiri T, Kondo E, Fujimaki K, Ueda Y, Aoyama Y, Ohtake S, Takita J, Sai E, Taniwaki M, Kurokawa M, Morishita S, Fukayama M, Kiyoi H, Miyazaki Y, Naoe T, Mano H.
  • Journal Title: Nat Genet. Volume: 48 Pages: 569-74
  • DOI: 10.1038/ng1216-1587a
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Mutational landscape and antiproliferative functions of ELF transcription factors in human cancer. (2016)
  • Author(s): Ando M, Kawazu M, Ueno T, Koinuma D, Ando K, Koya J, Kataoka K, Yasuda T, Yamaguchi H, Fukumura K, Yamato A, Soda M, Sai E, Yamashita Y, Asakage T, Miyazaki Y, Kurokawa M, Miyazono K, Nimer SD, Yamasoba T, Mano H.
  • Journal Title: Cancer Res. Volume: 76 Pages: 1814-1824
  • DOI: 10.1158/0008-5472.can-14-3816
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Genomic characterization of primary central nervous system lymphoma. (2016)
  • Author(s): Fukumura K, D Kawazu M, Ueno T, Sai E, Soda M, Kojima S, Ueda H, Yasuda T, Yamaguchi H, Lee J, Shishido-Hara Y, Sasaki A, Shirahata M, Mishima K, Ichimura K, Mukasa A, Narita Y, Saito N, Aburatani H, Nishikawa R, Nagane M, Mano H
  • Journal Title: Acta Neuropathol. Volume: publish online 12 Jan 2016 Pages: 865-75
  • DOI: 10.1007/s00401-016-1536-2
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] MicroRNA-31 is a positive modulator of endothelial-mesenchymal transition and associated secretory phenotype induced by TGF-β. (2016)
  • Author(s): Katsura A, Suzuki HI, Ueno T, Mihira H, Yamazaki T, Yasuda T, Watabe T, Mano H, Yamada Y, Miyazono K.
  • Journal Title: Genes Cells. Volume: 21 Pages: 99-116
  • DOI: 10.1111/gtc.12323
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] High Expression of MEF2D-Fusion Protein Is Caused By Escaping from the Suppression By miRNA and Leads to Suppress Transcriptional Activity of PAX5 (2017)
  • Author(s): Daiki Hirano, Fumihiko Hayakawa, Takahiko Yasuda, naoyuki Tange, Hideyuki Yamamoto, Yuki Kojima, Takanobu Morishita, Naoto Imoto, Shinobu Tsuzuki, Hiroyuki Mano, Tomoki Naoe, Hitoshi Kiyoi
  • Organizer: 59th Annual Meeting of American Society of Hematology
  • Int'l Joint Research
• [Presentation] The attempt to identify suitable MRD markers in acute lymphoblastic leukemia by next generation sequencing for practical use (2017)
  • Author(s): MitsukoAkaihata,YukaIijima,DaiNishijima,TomomiIshida,Mika Fuyama, Masaya Koganesawa, Takahiko Yasuda, Masashi Sanada
  • Organizer: 第５９回小児血液がん学会学術集会
• [Presentation] MEF2D 融合タンパクはマイクロ RNA の制御を 回避することで高発現になり PAX5 の転写活性 を抑制する (2017)
  • Author(s): Daiki Hirano, Fumihiko Hayakawa, Takahiko Yasuda, Hideyuki Yamamoto, Yuki Kojima, Takanobu Morishita, Naoto Imoto, Shinobu Tsuzuki, Hiroyuki Mano, Tomoki Naoe, Hitoshi Kiyoi
  • Organizer: 第79回日本血液学会学術集会
• [Presentation] 思春期・若年成人急性リンパ性白血病における新規融合型がん遺伝子DUX4-IGHの発見 (2016)
  • Author(s): 安田 貴彦、都築 忍、河津 正人、早川 文彦、小島 進也、上野 敏秀、清井 仁、直江 知樹、間野 博行
  • Organizer: 第75回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Invited
• [Book] 白血病診療の実際 (2017)
  • Author(s): 安田貴彦
  • Total Pages: 208
  • Publisher: 日本医師会雑誌
• [Book] AYA世代ALLのゲノム異常 (2016)
  • Author(s): 安田貴彦
  • Total Pages: 211
  • Publisher: 腫瘍内科
• [Book] Annual Review 2016 (2016)
  • Author(s): 安田貴彦
  • Total Pages: 234
  • Publisher: 中外医学社