Leukemic stem cell and genetic analysis in Juvenile myelomonocytic Leukemia

• Project/Area Number: 26461575
• 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): 小池 健一 信州大学, 医学部, 特任教授 (40143979)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: 若年性骨髄単球性白血病 / 白血病幹細胞 / PCDH17 / 白血病性幹細胞 / 若年性骨髄単球白血病 / 幹細胞

Outline of Final Research Achievements

Juvenile myelomonocytic leukemia (JMML) is a rare myelodyasplastic/myeloproliferative disorder that occurs during infancy and early childhood. Clonogenic JMML progenitors cannot be maintained in culture because they differentiate and the leukemic clone is lost within a few weeks. Here, we demonstrated that AGM-S3 in combination with hematopoietic growth factors expand CD34+CD38－ cells in patients with JMML showing PTPN11, NRAS, or KRAS mutation in the fetal bovine serum-containing culture.
From genome-wide DNA methylation analysis, we demonstrated that there was a significant correlation between methylation status of PCDH17 and event-free survival or overall survival in ALL. PCDH17 methylation at onset may be related to poor prognosis, and a new biomarker to predict relapse in ALL. PCDH17 gene may function as a tumor suppressor gene in leukemic cells. Now we examine the rule of PCDH17 gene in JMML.

Research Products

• [Journal Article] Aberrant methylation of protocadherin 17 and its prognostic value in pediatric acute lymphoblastic leukemia (2017)
  • Author(s): Uyen TN, Sakashita K, Al-Kzayer LF, Nakazawa Y, Kurata T, Koike K.
  • Journal Title: Pediatric Blood & Cancer Volume: in press Issue: 3 Pages: 200-5
  • DOI: 10.1002/pbc.26259
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Diagnosis and Treatment of Juvenile Myelomonocytic Leukemia (2016)
  • Author(s): Sakashita K, Matsuda K, Koike K
  • Journal Title: Pediatr Int Volume: 58 Issue: 8 Pages: 681-90
  • DOI: 10.1111/ped.13068
  • Peer Reviewed / Open Access
• [Journal Article] Juvenile myelomonocytic leukemia (JMML): recent advances in molecular pathogenesis and treatment (2016)
  • Author(s): Sakashita K.
  • Journal Title: Rinsho Ketsueki Volume: 57 Issue: 2 Pages: 137-146
  • DOI: 10.11406/rinketsu.57.137
  • NAID: 130005132712
  • ISSN: 0485-1439, 1882-0824
• [Journal Article] In vitro expansion of CD34(+)CD38(-) cells under stimulation with hematopoietic growth factors on AGM-S3 cells in juvenile myelomonocytic leukemia. (2015)
  • Author(s): Sakashita K, Kato I, Daifu T, Saida S, Hiramatsu H, Nishinaka Y, Ebihara Y, Ma F, Matsuda K, Saito S, Hirabayashi K, Kurata T, Uyen Lt, Nakazawa Y, Tsuji K, Heike T, Nakahata T, Koike K.
  • Journal Title: Leukemia. Volume: 29(3) Issue: 3 Pages: 606-14
  • DOI: 10.1038/leu.2014.239
  • NAID: 120007110642
  • Peer Reviewed / Open Access