Development of new treatment for juvenile myelomonocytic leukemia focusing on hematopoietic microenvironment

• Project/Area Number: 17K10105
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Shinshu University
• Principal Investigator: Sakashita Kazuo 信州大学, 医学部附属病院, 特任研究員 (10345746)
• Co-Investigator(Kenkyū-buntansha): 中沢 洋三 信州大学, 学術研究院医学系, 教授 (60397312)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: ＰＣＤＨ１７ / PCDH17 / 白血病幹細胞 / 接着分子 / 若年性骨髄単球性白血病 / 造血環境 / 白血病性幹細胞

Outline of Final Research Achievements

The aim is to clarify the hematopoietic microenvironmental molecules involved in the onset or progression of JMML, and to try to develop a novel molecular targeted therapeutic drug that is related to various clinical features. We reported that the adhesion molecule; protocadherin (PCDH) 17 gene is involved in the development of leukemia. We also found that PCDH17 acts as a tumor suppressor gene in hematopoietic tumors, and reported its potential as a target for novel molecular therapy

Academic Significance and Societal Importance of the Research Achievements

近年、腫瘍においては増殖シグナルや腫瘍特異的発現分子を標的とした治療薬の開発がはが盛んに行われている。今回の研究の成果は従来細胞間接着分子として働いていると考えられているPCDH17が細胞増殖に深く関与し、がん抑制遺伝子としての働きがあることをみいだした。このことはPCDH17が新規の分子標的治療薬としての可能性を示したことは学術的に大きな意義があると考えられる。

Research Products

• [Journal Article] Comparative analysis of graft-versus-host disease prophylaxis with tacrolimus in combination with methylprednisolone or methotrexate after umbilical cord blood transplantation (2020)
  • Author(s): Shigemura T, Sakashita K, Okura E, Morita D, Komori K, Kurata T, Hirabayashi K, Saito S, Tanaka M, Yanagisawa R, Nakazawa Y. Comparative analysis of graft-versus-host disease prophylaxis with tacrolimus in combination with methylprednisolone or methotrexate after umbilical cord blood transplantation
  • Journal Title: Int J Hematol Volume: 111 Issue: 5 Pages: 702-710
  • DOI: 10.1007/s12185-020-02826-9
  • Peer Reviewed
• [Journal Article] Essential role of PTPN11 mutation in enhanced haematopoietic differentiation potential of induced pluripotent stem cells of juvenile myelomonocytic leukaemia. (2019)
  • Author(s): Shigemura T, Matsuda K, Kurata T, Sakashita K, Okuno Y, Muramatsu H, Yue F, Ebihara Y, Tsuji K, Sasaki K, Nakahata T, Nakazawa Y, Koike K
  • Journal Title: Br J Haematol Volume: 187 Issue: 2 Pages: 163-173
  • DOI: 10.1111/bjh.16060
  • Peer Reviewed / Open Access
• [Journal Article] Panobinostat inhibits the proliferation of CD34(+) CD38(-) cells under stimulation of hematopoietic growth factors on AGM-S3 cells in juvenile myelomonocytic leukemia. Pediatr Blood Cancer. (2018)
  • Author(s): Kurata T, Matsuda K, Hirabayashi K, Shigemura T, Sakashita K, Nakahata T, Koike K.
  • Journal Title: Pediatr Blood Cancer. Volume: 65
  • Peer Reviewed
• [Presentation] 若年性骨髄単球性白血病における晩期合併症全国調査 (2019)
  • Author(s): 大園秀一、坂下一夫、吉田奈央、角田治美、百名伸之、中山秀樹、渡邉健一郎、前田美穂
  • Organizer: 日本小児血液がん学会
• [Presentation] 2.MRD assessment of juvenile myelomonocytic leukemia using next-generation sequencing (2019)
  • Author(s): Noriko Kubota, Kazuo Sakashita, Nao Yoshida，Koshi Akahane , Takeshi Mori, Nobuhisa Takahashi, Atsushi Kikuta，Jun Kobayashi，Takashi Kurata，Eiko Hidaka,
  • Organizer: 日本血液学会