Molecular analysis of pediatric acute megakaryoblastic leukemia without Down syndrome

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K08157
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Jichi Medical University (2021-2023); Okayama University (2020)
• Principal Investigator: SHIMADA AKIRA 自治医科大学, 医学部, 教授 (70391836)
• Co-Investigator(Kenkyū-buntansha): 林 泰秀 群馬県衛生環境研究所, 研究企画係, 研究員 (30238133)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: AMKL / JAK阻害剤 / 次世代シーケンサー解析

Outline of Final Research Achievements

Gene panel analysis of 10 AMKL specimens revealed various gene mutations such as KIT, SPI1, GATA1, NCOR2, SETBP1, CSF3R, etc., but no commonality, suggesting a heterogenous disease.
We investigated the effects of novel agents in AMKL cell lines and found that JAK inhibitors were promising, so we investigated the impact of cytarabine and JAK inhibitors in six AMKL cell lines. In our 3D co-culture system with mesenchymal cells that mimics the bone marrow microenvironment, synergistic effects were observed in two cell lines, MOLM16 and MKPL1, and these two cell lines are now being tested in transplantation experiments in mice.

Free Research Field

小児科

Academic Significance and Societal Importance of the Research Achievements

非ダウン症の急性巨核芽球性白血病（AMKL）は予後不良であるが、遺伝子パネル解析から、変異は個々の症例で異なっていた。AMKL細胞株６種類でcytarabineとJAK阻害剤の効果について検討したところ、MOLM16とMKPL1の２種類の細胞株でシナジー効果を見られたため、この２株についてマウスの移植実験で検証中である。