Analysis of human haematopietic stem cell movement with PNH-type cell.

• Project/Area Number: 26860363
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Laboratory medicine
• Research Institution: Kanazawa University
• Principal Investigator: KATAGIRI Takamasa 金沢大学, 保健学系, 助教 (60621159)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 骨髄不全 / ヒト造血幹細胞 / PNH形質血球 / 造血環境 / マウス骨髄内移植

Outline of Final Research Achievements

The regulation of HSC (Haematopietic stem cell) differentiation was assessed by FCM (Flow cytometry) with a marker, PNH (paroxysmal nocturnal hemoglobinuria)-type cell, which was detected in 60 perentage of bone marrow failure patients. As investigated the percentage of PNH-type cell in various lineages of HSPC (haematopoietc stem progenitor cell), PNH-type cells were detected only 10 perentage in CMP (common myelod progenitors) fraction, however, the same percentage was detected in GMP and MEP as myeloid cells in peripheral blood. Additional genetic analysis to check driver mutation genes effect on the selective growth of PNH-type cell revealed the expression of a specific cytokine was enhanced. From the above, I concluded the differentiation of human HSC was regulated by some complicated factors including HSCs or some cytokines in bone marrow.

Research Products

• [Journal Article] Identification of an HLA class I allele closely involved in the autoantigen presentation in acquired aplastic anemia. (2017)
  • Author(s): Zaimoku Y, Takamatsu H, Hosomichi K, Ozawa T, Nakagawa N, Imi T, Maruyama H, Katagiri T, Kishi H, Tajima A, Muraguchi A, Kashiwase K, Nakao S
  • Journal Title: Blood. Volume: 印刷中 Pages: 2908-2916
  • DOI: 10.1182/blood-2016-11-752378
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Cyclosporine restores hematopoietic function by compensating for decreased Tregs in patients with pure red cell aplasia and acquired aplastic anemia. (2016)
  • Author(s): Dao AT, Yamazaki H, Takamatsu H, Sugimori C, Katagiri T, Maruyama H, Zaimoku Y, Maruyama K, Ly TQ, Espinoza L, Nakao S
  • Journal Title: Ann Hematol Volume: 95 Pages: 771-781
  • DOI: 10.1007/s00277-016-2629-7
  • Peer Reviewed
• [Journal Article] Clinical significance and origin of leukocytes that lack HLA-A allele expression in patients with acquired aplastic anemia. (2016)
  • Author(s): Maruyama H, Katagiri T, Kashiwase K, Shiina T, Sato-Otsubo A, Zaimoku Y, Maruyama K, Hosokawa K, Ishiyama K, Yamazaki H, Inoko H, Ogawa S, Nakao S
  • Journal Title: Exp Hematol Volume: 44 Pages: 931-939
  • DOI: 10.1016/j.exphem.2016.05.013
  • NAID: 120005895697
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Paroxysmal nocturnal hemoglobinuria induced by the occurrence of BCR-ABL in a PIGA mutant hematopoietic progenitor cell (2016)
  • Author(s): Tominaga R, Katagiri T, Kataoka K, Wee RK, Maeda A, Gomyo H, Mizuno I, Murayama T, Ogawa S, Nakao S.
  • Journal Title: Leukemia Volume: - Pages: 1208-1210
  • DOI: 10.1038/leu.2015.268
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Increased glycosylphosphatidylinositol-anchored protein-deficient granulocytes define a benign subset of bone marrow failures in patients with trisomy 8 (2015)
  • Author(s): Hosokawa K, Sugimori N, Katagiri T, Sasaki Y, Saito C, Seiki Y, Mochizuki K, Yamazaki H, Takami A, Nakao S.
  • Journal Title: Eur J Haematol Volume: 18 Pages: 230-238
  • DOI: 10.1111/ejh.12484
  • NAID: 120005661927
  • Peer Reviewed / Open Access
• [Presentation] HLA Class I Allele-Lacking Hematopoietic Stem/Progenitor Cells Support Long-Term Clonal Hematopoiesis without Oncogenic Driver Mutations in Acquired Aplastic Anemia. (2016)
  • Author(s): Tatsuya Imi, Takamasa Katagiri, Kazuyoshi Hosomichi, Noriharu Nakagawa, Yoshitaka Zaimoku, Ken Ishiyama, Atsushi Tajima and Shinji Nakao.
  • Organizer: 58th American Society of Hematology Annual Meeting
  • Place of Presentation: San Diego Convention Center (San Diego. USA)
  • Year and Date: 2016-12-03
  • Int'l Joint Research
• [Presentation] Relatively Low Sensitivity of CD109(-) Hematopoietic Stem/Progenitor Cells (HSPCs) to TGF-β: A Possible Mechanism Responsible for the Preferential Commitment of Piga Mutant HSPCs in Immune-Mediated Bone Marrow Failure. (2016)
  • Author(s): Noriharu Nakagawa, Kohei Hosokawa, Luis Espinoza, Kana Maruyama, Takamasa Katagiri, Hirohito Yamazaki and Shinji Nakao.
  • Organizer: 58th American Society of Hematology Annual Meeting
  • Place of Presentation: San Diego Convention Center (San Diego. USA)
  • Year and Date: 2016-12-03
  • Int'l Joint Research
• [Presentation] A GPI-AP deficiency does not confer resistance to CTL or NK cell killing on HSPCs in aplastic anemia. (2016)
  • Author(s): 中川 紀温、丸山 裕之、片桐 孝和、井美 達也、石山 謙、中尾 眞二.
  • Organizer: 第78回日本血液学会学術集会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-10-13
• [Presentation] HLA-class I-lacking HSPCs support long-term clonal hematopoiesis without driver mutations in AA. (2016)
  • Author(s): 井美 達也、中川 紀温、丸山 佳奈、材木 義隆、石山 謙、片桐 孝和、中尾 眞二.
  • Organizer: 第78回日本血液学会学術集会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-10-13
• [Presentation] 6pLOHによるHLA欠失が再生不良性貧血の非血縁者間同種造血幹細胞移植に及ぼす影響 (2016)
  • Author(s): 材木 義隆、中川 紀温、井美 達也、丸山 佳奈、丸山 裕之、片桐 孝和、高松 博幸、石山 謙、 山﨑 宏人、中尾 眞二
  • Organizer: 第38回日本造血移植学会総会
  • Place of Presentation: 名古屋国際会議場（愛知県）
  • Year and Date: 2016-03-03
• [Presentation] A Cure for Paroxysmal Nocturnal Hemoglobinuria Using Molecular Targeted Therapy Specific to a Driver Mutation. Poster Presentation. (2015)
  • Author(s): Takamasa Katagiri, Ryo Tominaga, Keisuke Kataoka, Akio Maeda, Hiroshi Gomyo, Ishikazu Mizuno2, Tohru Murayama, Seishi Ogawa and Shinji Nakao.
  • Organizer: 57th American Society of Hematology Annual Meeting
  • Place of Presentation: Orange County Convention Center (Orlando)
  • Year and Date: 2015-12-03
  • Int'l Joint Research
• [Presentation] Evidence That T Cells Specific for Non-Hematopoietic Cells Trigger the Development of Acquired Aplastic Anemia. (2015)
  • Author(s): Tatsuya Imi, Hiroyuki Maruyama, Takamasa Katagiri, Yoshitaka Zaimoku, Kana Maruyama, Noriharu Nakagawa, Kohei Hosokawa, Ken Ishiyama, Hirohito Yamazaki, Koichi Kashiwase, and Shinji Nakao
  • Organizer: 57th American Society of Hematology Annual Meeting
  • Place of Presentation: Orange County Convention Center (Orlando)
  • Year and Date: 2015-12-03
  • Int'l Joint Research
• [Presentation] Evidence for a Common Immune Pathophysiology in Acquired Aplastic Anemia and Ulcerative Colitis (2015)
  • Author(s): Noriharu Nakagawa, Hiroyuki Maruyama, Yoshitaka Zaimoku, Kana Maruyama, Chizuru Saito, Takamasa Katagiri, , Kohei Hosokawa, Ken Ishiyama, Hirohito Yamazaki and Shinji Nakao.
  • Organizer: 57th American Society of Hematology Annual Meeting
  • Place of Presentation: Orange County Convention Center (Orlando)
  • Year and Date: 2015-12-03
  • Int'l Joint Research
• [Presentation] Generation of Ips Cell-Derived Hematopoietic Progenitor Cells from Patients with Acquired Aplastic Anemia Harboring Copy Number Neutral Loss of Heterozygosity of the Short Arm of Chromosome 6. (2015)
  • Author(s): Luis Espinoza, Yoshinori Yoshida, Kazuhisa Chonabayashi, Takamasa Katagiri, Yoshitaka Zaimoku and Shinji Nakao.
  • Organizer: 57th American Society of Hematology Annual Meeting
  • Place of Presentation: Orange County Convention Center (Orlando)
  • Year and Date: 2015-12-03
  • Int'l Joint Research
• [Presentation] Evidence that hematopoietic progenitor cells support long term hematopoiesis in humans (2015)
  • Author(s): 片桐 孝和、丸山 裕之, 材木 義隆, 丸山 佳奈, 石山 謙, 近藤 恭夫, 大竹 茂樹, 中尾 眞二
  • Organizer: 第77回日本血液学会学術集会
  • Place of Presentation: 石川県立音楽堂（石川県）
  • Year and Date: 2015-10-16
• [Presentation] HLA-A allele-lacking leukocytes as a therapeutic response marker in patients with aplastic anemia (2015)
  • Author(s): 丸山 裕之、片桐 孝和、材木 義隆、丸山 佳奈、山﨑 宏人、中尾 眞二
  • Organizer: 第77回日本血液学会学術集会
  • Place of Presentation: 石川県立音楽堂（石川県）
  • Year and Date: 2015-10-16
• [Presentation] Whole blood transcriptional profiling for diagnosing autoimmune hematopoietic failure (2015)
  • Author(s): 材木 義隆、中川 紀温、井美 達也、丸山 佳奈、丸山 裕之、片桐 孝和、高松 博幸、石山 謙、 山﨑 宏人、中尾 眞二
  • Organizer: 第77回日本血液学会学術集会
  • Place of Presentation: 石川県立音楽堂（石川県）
  • Year and Date: 2015-10-16
• [Presentation] デジタルPCRを用いた6pLOHによるHLA欠失血球の検出 (2015)
  • Author(s): 材木 義隆、中川 紀温、井美 達也、本宮 佳奈、丸山 裕之、片桐 孝和、高松 博幸、柏瀬 貢一、中尾 眞二
  • Organizer: 第7回血液疾患免疫療法研究会学術集会
  • Place of Presentation: 東京大学（東京都）
  • Year and Date: 2015-09-26
• [Presentation] Hematopoiesis in Patients with Acquired Aplastic Anemia Is Supported By a Limited Number of CXCR4(-) Cells at the Common Myeloid Progenitor Level (2014)
  • Author(s): Takamasa Katagiri, Atsuo Kasada, Kana Motomiya, Yoshitaka Zaimoku, An T. T. Dao, Hiroyuki Maruyama, Ken Ishiyama, Shigeki Ohtake, Atsushi Hirao, Shinji Nakao
  • Organizer: 56th American Society of Hematology Annual Meeting
  • Place of Presentation: Moscone Center (San Francisco)
  • Year and Date: 2014-12-06 – 2014-12-09
• [Presentation] Chronological Analysis of Clonal Evolution in Acquired Aplastic Anemia. (2014)
  • Author(s): Tetsuichi Yoshizato, Bogdan Dumitriu, Hideki Makishima, Takamasa Katagiri, Ayana Kon, Michael Clemente, Masashi Sanada, Satoru Miyano, Jaroslaw P. Maciejewski, Shinji Nakao, Neal S. Young, Seishi Ogawa.
  • Organizer: 56th American Society of Hematology Annual Meeting
  • Place of Presentation: Moscone Center (San Francisco)
  • Year and Date: 2014-12-06 – 2014-12-09
• [Presentation] A Profound Decrease in FoxP3+Helios+CD4+ T Cells in a Subset of Patients with Acquired Aplastic Anemia and Pure Red Cell Aplasia: A Common Mechanism Underlying a Dependency on Cyclosporine (2014)
  • Author(s): An T. T. Dao, Kohei Hosokawa, Chiharu Sugimori, Luis J. Espinoza, Kana Maruyama, Yoshitaka Zaimoku, Hiroyuki Maruyama, Takamasa Katagiri, Hirohito Yamazaki, Hiroyuki Takamatsu, Chizuru Saito, Noriko Iwaki, Shinji Nakao.
  • Organizer: 56th American Society of Hematology Annual Meeting
  • Place of Presentation: Moscone Center (San Francisco)
  • Year and Date: 2014-12-06 – 2014-12-09
• [Presentation] Resistance of Hematopoietic Stem Cells Lacking the KIR Ligand to Autologous NK Cell Attacks in Patients with Acquired Aplastic Anemia (2014)
  • Author(s): Hiroyuki Maruyama, Luis J. Espinoza, Takamasa Katagiri, Yoshitaka Zaimoku, Koichi Kashiwase Hiroo Saji, Seishi Ogawa, Shinji Nakao.
  • Organizer: 56th American Society of Hematology Annual Meeting
  • Place of Presentation: Moscone Center (San Francisco)
  • Year and Date: 2014-12-06 – 2014-12-09
• [Presentation] Donor-Type Aplastic Anemia after Allogeneic Hematopoietic Stem Cell Transplantation: A Common Cause of Late Graft Failure in Patients with Complete Donor Chimerism (2014)
  • Author(s): Kana Maruyama, Hiroyuki Maruyama, Yoshitaka Zaimoku, An T. T. Dao, Takamasa Katagiri, Hirohito Yamazaki, Shinji Nakao
  • Organizer: 56th American Society of Hematology Annual Meeting
  • Place of Presentation: Moscone Center (San Francisco)
  • Year and Date: 2014-12-06 – 2014-12-09
• [Presentation] Evidence That HLA-B*40:02 and HLA-Α*31:01 Are Strongly Involved in the Presentation of Autoantigens to CTLs Responsible for the Development of Acquired Aplastic Anemia (2014)
  • Author(s): Yoshitaka Zaimoku, Hiroyuki Maruyama, Kana Maruyama, Takamasa Katagiri, An T. T. Dao, Hiroyuki Takamatsu, Hirohito Yamazaki, Koichi Kashiwase, Shinji Nakao.
  • Organizer: 56th American Society of Hematology Annual Meeting
  • Place of Presentation: Moscone Center (San Francisco)
  • Year and Date: 2014-12-06 – 2014-12-09
• [Presentation] Complete chronological history of clonal evolution in sMDS from acquired aplastic anemia (2014)
  • Author(s): 吉里 哲一、Bogdan Dumitriu、細川 晃平、牧島 秀樹、吉田 健¹、奥野 友介、千葉 健一、田中 洋子、白石 友一、永田 安伸、片桐 孝和、昆 彩奈、Michael Clemente、真田 昌、宮野 悟、中尾 眞二、Jaroslaw Maciejewski、Neal Young、小川 誠司
  • Organizer: 第76回日本血液学会学術集会
  • Place of Presentation: 大阪国際会議場（大阪府）
  • Year and Date: 2014-10-31 – 2014-11-02
• [Presentation] A simple method to detect 6pLOH in patients with aplastic anemia using duplex quantitative PCR (2014)
  • Author(s): 材木 義隆、丸山 裕之、片桐 孝和、本宮 佳奈、齊藤 千鶴、高松 博幸、山崎 宏人、柏瀬 貢一、中尾 眞二
  • Organizer: 第76回日本血液学会学術集会
  • Place of Presentation: 大阪国際会議場（大阪府）
  • Year and Date: 2014-10-31 – 2014-11-02
• [Presentation] Evidence for a common immune pathophysiology in acquired aplastic anemia and ulcerative colitis (2014)
  • Author(s): 丸山 裕之、材木 義隆、本宮 佳奈、斉藤 千鶴、細川 晃平、片桐 孝和、山崎 宏人、中尾 眞二.
  • Organizer: 第76回日本血液学会学術集会
  • Place of Presentation: 大阪国際会議場（大阪府）
  • Year and Date: 2014-10-31 – 2014-11-02
• [Presentation] Complete resolution of PNH induced by nilotinib in a patient complicated by CML (2014)
  • Author(s): 富永 亮、前田 彰男、五明 広志、水野 石一、村山 徹、片桐 孝和、中尾 眞二
  • Organizer: 第76回日本血液学会学術集会
  • Place of Presentation: 大阪国際会議場（大阪府）
  • Year and Date: 2014-10-31 – 2014-11-02
• [Presentation] A simple method to detect copy number-neutral 6p-loh in patients with acquired aplastic anemia using duplex quantitative PCR (2014)
  • Author(s): Yoshitaka Zaimoku, Hiroyuki Maruyama, Ayaka Amano, Noriharu Nakagawa, Chizuru Saito, Takamasa Katagiri, Hiroyuki Takamatsu, Hirohito Yamazaki, Koichi Kashiwase, Shinji Nakao
  • Organizer: 19th European Hematology Association
  • Place of Presentation: Milano Congressi (Milan)
  • Year and Date: 2014-06-12 – 2014-06-15
• [Remarks] 金沢大学研究者情報
  • URL: http://ridb.kanazawa-u.ac.jp/public/detail.php?id=4033