Development of Novel Leukemia Therapeutics Targeting Circadian Rhythm Regulatory Molecules

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K15392
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52010:General internal medicine-related
• Research Institution: Kyushu University
• Principal Investigator: Kimura Tomoko (兵田朋子) 九州大学, 医学研究院, 助教 (20632772)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 概日リズム / 急性白血病 / CK2 / ミトコンドリア代謝

Outline of Final Research Achievements

In human and mouse hematologic tumor cell lines, inhibition of circadian rhythm regulators with the new compound had a growth inhibitory effect and loss or prolongation of circadian rhythm was observed in the spleen and bone marrow of leukemic mice. Gene expression analysis showed that factors related to mitochondrial function were significantly decreased. It was suggested that the anti-tumor effect may be caused by induction of metabolic and proliferative inhibition by reducing mitochondrial function in leukemia cells.

Free Research Field

血液検査学

Academic Significance and Societal Importance of the Research Achievements

地球上に生息するほぼすべての生物が有する概日リズムは、様々な疾患の発病との関連が報告されている。我々は概日リズム調節因子を抑制する新規化合物が、抗白血病効果を持つことを示し、概日リズムと急性骨髄性白血病（AML）を直接関連付ける新たな作用機序の一端を解明した。現在使用されている抗がん剤とは異なる作用点を持つ、より選択性の高い抗白血病治療薬となる可能性が示唆された。