Leukemic stem cell and genetic analysis in Juvenile myelomonocytic Leukemia

2016 Fiscal Year Final Research Report

• 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)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 若年性骨髄単球性白血病 / 白血病幹細胞 / PCDH17

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.

Free Research Field

小児血液腫瘍