Elucidation of the molecular pathogenesis of chronic myelomonocytic leukemia

• Project/Area Number: 18K16109
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: The University of Tokyo
• Principal Investigator: Yamazaki Sho 東京大学, 医学部附属病院, 助教 (00779407)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 慢性骨髄単球性白血病 / 細胞骨格

Outline of Final Research Achievements

Chronic myelomonocytic leukemia (CMML) is a hematopoietic malignancy with a poor prognosis, and the development of targeted therapies is required. The expression level of cytoskeleton-related genes in CMML cells is higher than that of healthy bone marrow cells, so we investigated whether these genes could be a potential therapeutic target. Regulation of the transcription level of these genes did not alter functions such as leukemogenesis or hematopoietic differentiation, and we are making preparations for experiments using knockout cells and metabolome analysis.

Academic Significance and Societal Importance of the Research Achievements

慢性骨髄単球性白血病（CMML）は予後不良の血液がんの一つであり、根治治療は同種造血幹細胞移植のみである。より副作用の少ない標的治療が求められており、CMML細胞において発現レベルの高い、細胞骨格に関わる遺伝子群に注目している。本研究では、これらの遺伝子の発現レベルの調節により白血病発症能や血球分化能に明らかな影響を与えることは示されなかったが、今後遺伝子のノックアウト実験やタンパク質レベルの代謝に注目した解析を行うことで治療標的となりうるかを示せる可能性がある。