Identification of human hematopoietic stem cell regulators with HLA allele deficient cells behavior

• Project/Area Number: 24790968
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Hematology
• Research Institution: Kanazawa University
• Principal Investigator: KATAGIRI Takamasa 金沢大学, 保健学系, 助教 (60621159)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2013: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2012: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
• Keywords: Loss of heterogeneity / Aplastic anemia / Human Leukocyte Antigen / 病態検査学 / 血液内科学 / 免疫学 / 再生不良性貧血 / uniparental disomy / HLA

Research Abstract

The percentage of 6pLOH was different among hematopoiesis stages in human bone marrow, and the progenitor cells showed much lower percentage of 6pLOH than that of MEP and GMP.
I found approximately 30 times lower expression of CXCL12 which promotes the cell growth and proliferation cytokine than that of normal fraction with microarray analysis. As a result, I demonstrated the percentage of HLA deficient was significantly decreased, since the cell cycle was not promoted in the 6pLOH of CMP fraction with low CXCL12 and CXCR4 expression.

Research Products

• [Journal Article] Individual hematopoietic stem cells in bone marrow of patients with aplastic anemia or myelodysplastic syndrome stably give rise to limited cell lineages (2013)
  • Author(s): Takamasa Katagiri, Hiroshi Kawamoto,Takashi Nakakuki, Ken Ishiyama, Mariko Okada-Hatakeyama, Shigeki Ohtake, Yu Seiki, Kohei Hosokawa, Shinji Nakao
  • Journal Title: Stem Cells Volume: 31(3) Pages: 536-546
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/23316019
  • Peer Reviewed
• [Journal Article] Individual hematopoietic stem cells in human bone marrow of patients with aplastic anemia or myelodysplastic syndrome stably give rise to limited cell lineages (2013)
  • Author(s): Takamasa Katagiri, Hiroshi Kawamoto, Takashi Nakakuki, Ken Ishiyama, Mariko Okada-Hatakeyama, Shigeki Ohtake, Yu Seiki, Kohei Hosokawa and Shinji Nakao
  • Journal Title: STEM CELLS Volume: 31 Pages: 536-546
  • NAID: 120005253838
  • Peer Reviewed
• [Journal Article] Individual hematopoietic stem cells in human bone marrow of patients with aplastic anemia or myelodysplastic syndrome stably give rise to limited cell lineages. (2013)
  • Author(s): Katagiri T, et al.
  • Journal Title: Stem Cells Volume: 31 Issue: 3 Pages: 536-46
  • DOI: 10.1002/stem.1301
  • Peer Reviewed
• [Journal Article] Favorable outcome of patients who have 13q deletion : a suggestion for revision of the WHO 'MDS-U' designation (2012)
  • Author(s): Kohei Hosokawa, Takamasa Katagiri,Naomi Sugimori, Ken Ishiyama, Yumi Sasaki,Yu Seiki, Aiko Sato-Otsubo, Masashi Sanada,Seishi Ogawa, Shinji Nakao
  • Journal Title: Haematologica Volume: 97(12) Pages: 1845-1849
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/22689682
  • Peer Reviewed
• [Journal Article] Immunologically escaped hematopoiesis caused by HLA allelic loss in patients with aplastic anemia (2012)
  • Author(s): Takamasa Katagiri, Shinji Nakao
  • Journal Title: Rinsho Ketsueki Volume: 53(7) Pages: 651-657
  • NAID: 10030990141
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/22975765
  • Peer Reviewed
• [Journal Article] Immunologically escaped hematopoiesis caused by HLA allelic loss in patients with aplastic anemia (2012)
  • Author(s): Katagiri T, Nakao S
  • Journal Title: Rinsho Ketsueki Volume: 53 Pages: 651-657
  • NAID: 10030990141
  • Peer Reviewed
• [Journal Article] Favorable outcome of patients who have 13q deletion: a suggestion for revision of the WHO 'MDS-U' designation. (2012)
  • Author(s): Hosokawa K, et al.
  • Journal Title: Haematologica Volume: 97 Issue: 12 Pages: 1845-9
  • DOI: 10.3324/haematol.2011.061127
  • Peer Reviewed
• [Presentation] Hematopoietic stem cells deficient of inhibitory KIR ligands due to uniparental disomy in the short arm of chromosome 6 escape from the autologous NK cell attack in humans (2014)
  • Author(s): 丸山 裕之
  • Organizer: 第38回日本造血幹細胞移植学会
  • Place of Presentation: 沖縄コンベンションセンター(沖縄)
• [Presentation] Hematopoietic stem cells deficient of inhibitory KIR ligands due to uniparental disomy in the short arm of chromosome 6 escape from the autologous NK cell attack in humans (2014)
  • Author(s): 丸山 裕之、佐治 博夫、屋部登志雄、柏瀬 貢一、片桐 孝和、材木 義隆、斉藤 千鶴、細川 晃平、山崎 宏人、小川 誠司、中尾 眞二
  • Organizer: 第38回日本造血幹細胞移植学会
  • Place of Presentation: 沖縄コンベンションセンター(沖縄県)
• [Presentation] Evidence That GPI-AP-Specific Are Not Involved In The "escape"Of Piga mutant Hematopoietic Stem Cells in Aplastic Anemia (2013)
  • Author(s): Takamasa Katagiri
  • Organizer: 55th American Society of hematology Annual Meeting
  • Place of Presentation: Ernest N. Morial Convention Center (New Orleons.USA)
• [Presentation] Increased Gene Expression Of the Nr4A Family In Bone Marrow T Cells Of Patients With Early Stage Acquired Aplastic Anemia (2013)
  • Author(s): Kohei Hosokawa
  • Organizer: 55th American Society of hematology Annual Meeting
  • Place of Presentation: Ernest N. Morial Convention Center (New Orleons.USA)
• [Presentation] Prevalence, Clone Size and Lineage Diversity Of HLA-A Allele-Lacking Leukocytes In Patients With Acquired Aplastic Anemia (2013)
  • Author(s): Hiroyuki Maruyama
  • Organizer: 55th American Society of hematology Annual Meeting
  • Place of Presentation: Ernest N. Morial Convention Center (New Orleons.USA)
• [Presentation] Spectrum Of Genetic Alterations In Acquired Aplastic Anemia (2013)
  • Author(s): Tetsuichi Yoshizato
  • Organizer: 55th American Society of hematology Annual Meeting
  • Place of Presentation: Ernest N. Morial Convention Center (New Orleons.USA)
• [Presentation] Evidence that HSCs are redundant and only a limited number of HSCs support hematopoiesis in humans (2013)
  • Author(s): Takamasa Katagiri
  • Organizer: 第75回日本血液学会学術集会
  • Place of Presentation: ロイトン札幌, 札幌芸人館, 札幌市教育文化会館(北海道)
• [Presentation] Isolation of a HLA-B*4002-restricted CTL to HPCs from a patient with aplastic anemia with 6pLOH (2013)
  • Author(s): Yoshiki Akatsuka
  • Organizer: 第75回日本血液学会学術集会
  • Place of Presentation: ロイトン札幌, 札幌芸人館, 札幌市教育文化会館(北海道)
• [Presentation] Escape hematopoiesis by HSC with somatic SLIT1 mutations in patients with acquired aplastic anemia (2013)
  • Author(s): Chizuru Saito
  • Organizer: 第75回日本血液学会学術集会
  • Place of Presentation: ロイトン札幌, 札幌芸人館, 札幌市教育文化会館(北海道)
• [Presentation] Spectrum of alterations in acquired aplastic anemia (2013)
  • Author(s): Tetsuichi Yoshizato
  • Organizer: 第75回日本血液学会学術集会
  • Place of Presentation: ロイトン札幌, 札幌芸人館, 札幌市教育文化会館(北海道)
• [Presentation] Prevalence of HLA-A allele lacking leukocytes in patients with aplastic anemia at diagnosis (2013)
  • Author(s): Hiroyuki Maruyama
  • Organizer: 第75回日本血液学会学術集会
  • Place of Presentation: ロイトン札幌, 札幌芸人館, 札幌市教育文化会館(北海道)
• [Presentation] The CTL attack specific for non-HSC in bone marrow induces aplastic anemia (2013)
  • Author(s): 丸山 裕之
  • Organizer: 第5回造血器腫瘍免疫療法研究会学術集会
  • Place of Presentation: ウィンク愛知(愛知)
• [Presentation] SPECTRUM OF GENETIC ALTERATIONS IN ACQUIRED APLASTIC ANEMIA (2013)
  • Author(s): Tetsuichi Yoshizato
  • Organizer: 18th EUROPEAN HEMATOLOGY ASSOCIATION
  • Place of Presentation: Stockholm International Fairs & Congress Centre (スウェーデン)
• [Presentation] Detection of leukocytes lacking HLA-A alleles by flow cytometry predicts a response to immunosuppressive therapy in patients with aplastic anemia (2013)
  • Author(s): Hiroyuki Maruyama
  • Organizer: 39th Annual meeting of the European Group for Blood and Marrow Transplantaion
  • Place of Presentation: Excel London (England)
• [Presentation] Evidence That GPI-AP-Specific CTLs Are Not Involved In The “escape” Of Piga mutant Hematopoietic Stem Cells In Aplastic Anemia (2013)
  • Author(s): Takamasa Katagiri, Hiroyuki Maruyama, Shigeki Ohtake, Chizuru Saito, Kohei Hosokawa, Seishi Ogawa, and Shinji Nakao
  • Organizer: 55th American Society of Hematology Annual Meeting
  • Place of Presentation: Ernest N. MorialConvention Center (New Orleons. USA)
• [Presentation] Increased Gene Expression Of The Nr4A Family In Bone Marrow T Cells Of Patients With Early Stage Acquired Aplastic Anemia (2013)
  • Author(s): Kohei Hosokawa, Takamasa Katagiri, Chizuru Saito, Hiroyuki Maruyama, Naomi Sugimori, Hirohito Yamazaki, and Shinji Nakao
  • Organizer: 55th American Society of Hematology Annual Meeting
  • Place of Presentation: Ernest N. MorialConvention Center (New Orleons. USA)
• [Presentation] Prevalence, Clone Size and Lineage Diversity Of HLA-A Allele-Lacking Leukocytes In Patients With Acquired Aplastic Anemia (2013)
  • Author(s): Hiroyuki Maruyama, Takamasa Katagiri, Yoshitaka Zaimoku, , Chizuru Saito, , Kohei Hosokawa, , Hirohito Yamazaki, , Seishi Ogawa Shinji Nakao
  • Organizer: 55th American Society of Hematology Annual Meeting
  • Place of Presentation: Ernest N. MorialConvention Center (New Orleons. USA)
• [Presentation] Spectrum Of Genetic Alterations In Acquired Aplastic Anemia (2013)
  • Author(s): Tetsuichi Yoshizato, Bogdan Dumitriu, Takamasa Katagiri, Ayana Kon, Michael J. Clemente, Masashi Sanada, Satoru Miyano, Jaroslaw P. Maciejewski, Shinji Nakao, Neal S. Young and Seishi Ogawa
  • Organizer: 55th American Society of Hematology Annual Meeting
  • Place of Presentation: Ernest N. MorialConvention Center (New Orleons. USA)
• [Presentation] Detection of leukocytes lacking HLA-A alleles by flow cytometry predicts a response to immunosuppressive therapy in patients with aplastic anemia (2013)
  • Author(s): Hiroyuki Maruyama, Takamasa Katagiri, Kohei Hosokawa, Chizuru Saito, Hirohito Yamazaki, Shinji Nakao
  • Organizer: 39th Annual meeting of the European Group for Blood and Marrow Transplantation, Hematology Medical Congress
  • Place of Presentation: Excel London （イギリス）
• [Presentation] SPECTRUM OF GENETIC ALTERATIONS IN ACQUIRED APLASTIC ANEMIA (2013)
  • Author(s): Tetsuichi Yoshizato, Kohei Hosokawa, Kenichi Yoshida, Yusuke Okuno, Kenichi Chiba, Hiroko Tanaka, Yuichi Shiraishi, Yasunobu Nagata, Takamasa Katagiri, Ayana Kon, Masashi Sanada, Satoru Miyano, Shinji Nakao, Seishi Ogawa
  • Organizer: 18th EUROPEAN HEMATOLOGY ASSOCIATION
  • Place of Presentation: Stockholm International Fairs & Congress Centre （スウェーデン）
• [Presentation] The CTL attack specific for non-HSCs in bone marrow induces aplastic anemia. (2013)
  • Author(s): 丸山 裕之、片桐 孝和、中尾 眞二
  • Organizer: 第5回造血器腫瘍免疫療法研究会学術集会
  • Place of Presentation: ウインク愛知（愛知）
• [Presentation] Evidence that HSCs are redundant and only a limited number of HSCs support hematopoiesis in humans (2013)
  • Author(s): Takamasa katagiri, Chizuru Saito, Hiroyuki Maruyama, Kohei Hosokawa, Shigeki Ohtake, Hirohito Yamazaki, Shinji Nakao
  • Organizer: 第75回日本血液学会学術集会
  • Place of Presentation: ロイトン札幌、さっぽろ芸人館、札幌市教育文化会館（北海道）
• [Presentation] Isolation of a HLA-B*4002-restricted CTL to HPCs from a patient with aplastic anemia with 6pLOH (2013)
  • Author(s): Yoshiki Akatsuka, Kohei Hosokawa, Akinao Okamoto, Youko, Inaguma, Takamasa Katagiri, Ayako Demachi-Okamura, Kiyotaka Kuzushima, Nobuhiko Emi, Shinji Nakao
  • Organizer: 第75回日本血液学会学術集会
  • Place of Presentation: ロイトン札幌、さっぽろ芸人館、札幌市教育文化会館（北海道）
• [Presentation] Escape hematopoiesis by HSC with somatic SLIT1 mutaions in patients with acquired aplastic anemia (2013)
  • Author(s): Chizuru Saito, Kohei Hosokawa, Hiroyuki Maruyama, Takamasa Katagiri, Akinori Kanai, Hirotaka Matsui, Toshiya Inaba, Akari Kazami, Masafumi Taniwaki, Hirohito Yamazaki, Shinji Nakao
  • Organizer: 第75回日本血液学会学術集会
  • Place of Presentation: ロイトン札幌、さっぽろ芸人館、札幌市教育文化会館（北海道）
• [Presentation] Spectrum of genetic alterations in acquired aplastic anemia (2013)
  • Author(s): Tetsuichi Yoshizato, Takamasa Katagiri, Bogdan Dumitriu, Kenichi Yoshida, Yusuke Okuno, Kenichi Chiba, Hiroko Tanaka, Yuichi Shiraishi, Yasunobu Nagata, Ayana Kon, Masashi Sanada, Satoru Miyano, Neal Young, Shinji Nakao, Seishi Ogawa
  • Organizer: 第75回日本血液学会学術集会
  • Place of Presentation: ロイトン札幌、さっぽろ芸人館、札幌市教育文化会館（北海道）
• [Presentation] Prevalenece of HLA-A allele lacking leukocytes in patients with aplastic anemia at diagnosis (2013)
  • Author(s): Hiroyuki Maruyama, Takamasa Katagiri, Chizuru Saito, Kohei Hosokawa, Hirohito Yamazaki, Shinji Nakao
  • Organizer: 第75回日本血液学会学術集会
  • Place of Presentation: ロイトン札幌、さっぽろ芸人館、札幌市教育文化会館（北海道）
• [Presentation] Detection of leukocytes lacking HLA-A alleles by flow cytometry predicts a response to immunosuppressive therapy in patients with aplastic anemia (2013)
  • Author(s): H Maruyama, T Katagiri, K Hosokawa, C Saito, H Yamazaki, S Nakao.
  • Organizer: 39th Annual meeting of the European Group for Blood and Marrow Transplantation.
  • Place of Presentation: ExCel London (London)
• [Presentation] SLIT1 Mutation in Patients with Acquired Aplastic Anemia : Its Relevance in Immune Pathophysiology (2012)
  • Author(s): Chizuru Saito
  • Organizer: 54th American society of Hematology Annual meeting
  • Place of Presentation: Georgia World Congress (Atlanta)
• [Presentation] GPI-AP specific CTL are not involved in the escape of PIGA mutant stem cells in aplastic anemia (2012)
  • Author(s): Takamasa Katagiri
  • Organizer: 第74回日本血液学会学術集会
  • Place of Presentation: 京都国際会館(京都)
• [Presentation] Spectrum of genetic alterations in aplastic anemia (2012)
  • Author(s): Tetsuichi Yodhizato
  • Organizer: 第74回日本血液学会学術集会
  • Place of Presentation: 京都国際会館(京都)
• [Presentation] CD109 deficiency induces preferential proliferation of PIGA mutant hematopoietic stem cell (2012)
  • Author(s): Kohei Hosokawa
  • Organizer: 第74回日本血液学会学術集会
  • Place of Presentation: 京都国際会館(京都)
• [Presentation] Clinical significance of plasma thrombopoietin levels in the management of bone marrow failure (2012)
  • Author(s): Chizuru Saito
  • Organizer: 第74回日本血液学会学術集会
  • Place of Presentation: 京都国際会館(京都)
• [Presentation] Minimum PNH clone size associated with clinical hemolysis in patients with bone marrow failure (2012)
  • Author(s): Hiroyuki Maruyama
  • Organizer: 第74回日本血液学会学術集会
  • Place of Presentation: 京都国際会館(京都)
• [Presentation] SLIT1 Mutation in Patients with Acquired Aplastic Anemia: Its Relevance in Immune Pathophysiology (2012)
  • Author(s): Chizuru Saito, Kohei Hosokawa, Takamasa Katagiri, Akinori Kanai, Hirotaka Matsui, Toshiya Inaba, Masafumi Taniwaki, Hirohito Yamazaki, and Shinji Nakao.
  • Organizer: 54th American Society of Hematology Annual Meeting
  • Place of Presentation: Georgia World Congress Center(Atlanta)
• [Presentation] GPI-AP specific CTL are not involved in the escape of PIGA mutant stem cells in aplastic anemia (2012)
  • Author(s): Takamasa Katagiri, Seishi Ogawa, Shigeki Ohtake, Yu Seiki, Kohei Hosokawa, Shinji Nakao
  • Organizer: 第74回日本血液学会学術集会
  • Place of Presentation: 京都国際会館（京都府）
• [Presentation] Spectrum of genetic alterations in aplastic anemia (2012)
  • Author(s): T Yoshizato, T Katagiri, K Yoshida, Y Okuno, K Chiba, H Tanaka, Y Shiraishi, Y Nagata, K Hosokawa, A Kon, M Sanada, S Miyano, S Nakao, S ogawa.
  • Organizer: 第74回日本血液学会学術集会
  • Place of Presentation: 京都国際会館（京都府）
• [Presentation] CD109 deficiency induces preferential proliferation of PIGA mutant hematopoietic stem cells (2012)
  • Author(s): Kohei Hosokawa, Takamasa Katagiri, Chizuru Saito, Espinoza Luis, Yumi Sasaki, Yu Seiki, Yasuhiko Yamamoto, Hirohito Yamazaki, Shinji Nakao.
  • Organizer: 第74回日本血液学会学術集会
  • Place of Presentation: 京都国際会館（京都府）
• [Presentation] Clinical significance of plasma thrombopoietin levels in the management of bone marrow failure (2012)
  • Author(s): Chizuru Saito, Kohei Hososkawa, Hiroyuki Maruyama, Yu Seiki, Takamasa Katagiri, Hiroyuki Takamatsu, Hirohito Yamazaki, Shinji Nakao
  • Organizer: 第74回日本血液学会学術集会
  • Place of Presentation: 京都国際会館（京都府）
• [Presentation] Minimum PNH clone size associated with clinical hemolysis in patients with bone marrow failure (2012)
  • Author(s): Hiroyuki Maruyama, Yumi Sasaki, Takamasa Katagiri, Kohei Hosokawa, Chizuru Saito, Yu Seiki, Kanako Mochizuki, Hiroyuki Takamatsu, Chiharu Sugimori, Hirohito Yamazaki, Shinji Nakao
  • Organizer: 第74回日本血液学会学術集会
  • Place of Presentation: 京都国際会館（京都府）
• [Book] 再生不良性貧血における6 番染色体短腕CNN-LOH によるHLA アレル欠失血球の出現とその臨床的意義, 臨床免疫・アレルギー科(Clinical Immunology & Allergology) (2013)
  • Author(s): 片桐 孝和
• [Book] 臨床免疫アレルギー科(Clinical Immunology & Allergoology) (2013)
  • Author(s): 片桐 孝和
  • Total Pages: 8
  • Publisher: 科学評論社
• [Remarks]
  • URL: http://research-er.jp/researchers/view/60621159/