Development of innovative molecular targeted therapeutics based on elucidation of dynamics of CML stem cells in hypoxic environment

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K07171
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor therapeutics
• Research Institution: Kyoto Prefectural Institute of Public Health and Environment (2018); Kyoto University (2016-2017)
• Principal Investigator: MAEKAWA TAIRA 京都府保健環境研究所, その他部局等, 所長 (80229286)
• Co-Investigator(Kenkyū-buntansha): 平位 秀世 京都大学, 医学研究科, 助教 (50315933)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 慢性骨髄性白血病 / 白血病幹細胞 / インターフェロン

Outline of Final Research Achievements

Chronic myelogenous leukemia (CML) has become an era of therapeutic remission and cure with tyrosine kinase inhibitors, and eradication of CML stem cells has become a pressing issue. Interferon (IFN) -α, which was once used as a first-line drug for CML treatment, has unknown mechanisms of action despite its cytogenetic effects in some cases. We attempted to elucidate the dynamics of CML stem cells in a hypoxic environment using hypoxic-adapted CML cell lines and patient cells that are "stem-like". As a result, it was revealed that IFN-α cooperates with BCR-ABL to activate the transcription factor C / EBPβ and induce the differentiation of CML stem cells into myeloid cells and their depletion.

Free Research Field

血液内科学

Academic Significance and Societal Importance of the Research Achievements

慢性骨髄性白血病の実験動物モデル及び患者から提供を受けた白血病細胞を用いて検討し、インターフェロンが白血病の原因遺伝子と協調して働き、白血病幹細胞の枯渇を誘導することがわかりました。白血病幹細胞は、白血病の治療抵抗性や再発の原因となると考えられており、本研究成果は一部の白血病においてインターフェロンを工夫して投与することによって治療成績がさらに改善する可能性を示唆するものです。