Roles of functionally disrupted niches on hematological malignancy

• Project/Area Number: 15H04859
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: Kyushu University
• Principal Investigator: Kunisaki Yuya 九州大学, 病院, 講師 (80737099)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000); Fiscal Year 2017: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2016: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000)
• Keywords: 造血幹細胞 / 白血病幹細胞 / 間葉系幹細胞 / 造血微小環境 / 白血病 / 骨髄微小環境 / 白血病ニッチ / がん幹細胞 / がん微小環境 / 加齢 / 造血器腫瘍 / 癌 / 幹細胞 / 微小環境 / 癌幹細胞 / 癌微小環境

Outline of Final Research Achievements

This study report that selected microenvironment exists and highlights the possibility of heterogeneity among mesenchymal niche cells. Recently, cellular heterogeneity within a tumor has been highlighted and among aggressively proliferating tumor cells, a small fraction is found in quiescent status, causing refractoriness to anti-cancer therapy and relapsed diseases. Even in cancer cells that appear to proliferate in an unlimited manner, environmental cues are believed to control their cell cycle status, quiescence or proliferation. Therefore, “decision” whether symmetric or asymmetric division is essential for leukemia to survive. The anatomical and functional interactions between hematopoietic cells or leukemia and their microenvironments are essential to efficiently control normal and pathological hematopoiesis. This study suggests that identification of the niches may add new concept as “anti-cancer niche” to cancer therapy.

Research Products

• [Journal Article] Identification of unipotent megakaryocyte progenitors in human hematopoiesis. (2017)
  • Author(s): K. Miyawaki. Iwasaki, T. Jiromaru, H. Kusumoto, A. Yurino, T. Sugio, Y. Uehara, J. Odawara, S. Daitoku, Y. Kunisaki, Y. Mori, Y. Arinobu, H. Tsuzuki, Y. Kikushige, T. Iino, K. Kato, K. Takenaka, T. Miyamoto, T. Maeda, *K. Akashi
  • Journal Title: Blood Volume: 印刷中 Issue: 25 Pages: 3332-3343
  • DOI: 10.1182/blood-2016-09-741611
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Differential cytokine contributions of perivascular haematopoietic stem cell niches. (2017)
  • Author(s): Asada N, Kunisaki Y, Pierce H, Wang Z, Fernandez NF, Birbrair A, Ma'ayan A, Frenette PS.
  • Journal Title: Nature Cell Biology Volume: 3 Issue: 3 Pages: 142-223
  • DOI: 10.1038/ncb3475
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Enhanced Reconstitution of Human Erythropoiesis and Thrombopoiesis in an Immunodeficient Mouse Model with Kit(Wv) Mutations. (2016)
  • Author(s): A. Yurino, K. Takenaka, T. Yamauchi, T. Nunomura, Y. Uehara, F. Jinnouchi, K. Miyawaki, Y. Kikushige, K. Kato, T. Miyamoto, H. Iwasaki, Y. Kunisaki, *K. Akashi
  • Journal Title: Stem Cell Reports Volume: 7 Issue: 3 Pages: 425-438
  • DOI: 10.1016/j.stemcr.2016.07.002
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Fetal liver hematopoietic stem cell niches associate with portal vessels (2016)
  • Author(s): Khan JA, Mendelson A, Kunisaki Y, Birbrair A, Kou Y, Arnal-Estapé A, Pinho S, Ciero P, Nakahara F, Ma'ayan A, Bergman A, Merad M, Frenette PS.
  • Journal Title: Science Volume: 351 Issue: 6269 Pages: 176-180
  • DOI: 10.1126/science.aad0084
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Neutrophil ageing is regulated by the microbiome (2015)
  • Author(s): Zhang D, Chen G, Manwani D, Mortha A, Xu C, Faith JJ, Burk RD, Kunisaki Y, Jang JE, Scheiermann C, Merad M, Frenette PS.
  • Journal Title: Nature Volume: 525 Issue: 7570 Pages: 528-532
  • DOI: 10.1038/nature15367
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Distinct vascular niches determine hematopoietic stem cell fate (2015)
  • Author(s): Kunisaki Y.
  • Journal Title: Rinsho Ketsueki Volume: 56 Issue: 6 Pages: 606-613
  • DOI: 10.11406/rinketsu.56.606
  • NAID: 130005093086
  • ISSN: 0485-1439, 1882-0824
• [Journal Article] Cancer stem cells and the niches (2015)
  • Author(s): Kunisaki Y.
  • Journal Title: Rinsho Ketsueki Volume: 73 Pages: 739-744
• [Presentation] 間葉系幹細胞による造血幹細胞制御機構 (2017)
  • Author(s): 國崎 祐哉
  • Organizer: 第122回日本解剖学会総会・全国学術集会
  • Invited
• [Presentation] 骨髄微小環境のイメージング (2016)
  • Author(s): 國崎 祐哉
  • Organizer: 第31回日本整形外科学会基礎学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2016-10-13
  • Invited
• [Presentation] 間葉系幹細胞による造血幹細胞制御機構 (2016)
  • Author(s): 國崎 祐哉
  • Organizer: 第60回日本リウマチ学会総会・学術集会
  • Place of Presentation: 東京
  • Year and Date: 2016-04-20
  • Invited
• [Presentation] 血管性ニッチによる造血幹細胞維持機構 (2015)
  • Author(s): 國崎 祐哉
  • Organizer: 第18回癌と骨病変研究会
  • Place of Presentation: 千代田放送会館、東京
  • Year and Date: 2015-11-13
  • Invited
• [Presentation] 造血幹細胞ニッチ (2015)
  • Author(s): 國崎 祐哉
  • Organizer: 第77回日本血液学会学術集会
  • Place of Presentation: 金沢
  • Year and Date: 2015-10-15
  • Invited
• [Presentation] Imaging of the bone marrow and hematopoietic stem cells (2015)
  • Author(s): Yuya Kunisaki
  • Organizer: 44th International society of experimental hematology annual meeting
  • Place of Presentation: Kyoto
  • Year and Date: 2015-09-17
  • Int'l Joint Research / Invited
• [Presentation] 骨髄微小環境による造血幹細胞制御機構 (2015)
  • Author(s): 國崎 祐哉
  • Organizer: 第39回阿蘇シンポジウム
  • Place of Presentation: 阿蘇リゾートグランヴィリオホテル、熊本
  • Year and Date: 2015-07-31
  • Invited
• [Presentation] 血管性ニッチによる造血幹細胞制御機構 (2015)
  • Author(s): 國崎 祐哉
  • Organizer: 第33回日本骨代謝学会学術集会
  • Place of Presentation: 京王プラザホテル、東京
  • Year and Date: 2015-07-23
  • Invited