Exploring biomarkers concerning NK immunity that favor treatment discontinuation in CML patients
| Project/Area Number |
17K09908
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Saga University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
安藤 寿彦 佐賀大学, 医学部, 准教授 (30363097)
久保田 寧 佐賀大学, 医学部, 講師 (60570413)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | 慢性骨髄性白血病 / チロシンキナーゼ阻害剤 / 免疫 / NK 免疫 / NK 細胞 / バイオマーカー |
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| Outline of Final Research Achievements |
We reported that patients with chronic myeloid leukemia (CML) who had polymorphisms such as KIR3DL1*005 on NK cells had significantly better response to tyrosine kinase inhibitors (TKIs) (Cancer Immunol Res 2018).
Based on the difference in the results of second-line dasatinib discontinuation study (Lancet Haematol 2015) and first-line dasatinib discontinuation study (Lancet Haematol 2020) both which we performed, we confirmed that the sustained molecular response after dasatinib discontinuation depended not on NK immunity but on T cell immunity (in submission).
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| Academic Significance and Societal Importance of the Research Achievements |
TKIs によってCMLの予後は格段に改善し、ほぼ健常人と同等の生命予後となった。しかし長期的な TKIs 服用による有害事象や高額な費用が問題となってきた。我々は、1次使用でも2次使用でも半数近い患者がダサチニブが中止できること、そして免疫細胞は効果発現と中止後の維持では、NK細胞とT細胞などの免疫細胞が役割分担しながら働いていることを明らかにした。
これらの結果は、CML患者の予後をさらに改善するでなく、個人の経済的負担そして国全体の医療費の削減にも貢献できる成果である。
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Report
(4 results)
Research Products
(19 results)
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[Journal Article] C/EBPβ is a critical mediator of IFNα-induced exhaustion of chronic myeloid leukemia stem cells.2019
Author(s)
Yokota A, Hirai H, Sato R, Adachi H, Sato F, Hayashi Y, Sato A, Kamino N, Miura Y, Nakano M, Tenen DG, Kimura S, Tashiro K, Maekawa T
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Journal Title
Blood Advances
Volume: 3
Issue: 3
Pages: 476-488
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] HMGCLL1 is a predictive biomarker for deep molecular response to imatinib therapy in chronic myeloid leukemia.2018
Author(s)
Park J.-H., Woo Y.-M., Youm E., Hamad N., Won H.-H., Naka K., Park E.-J., Park J.-H., Kim H.J., Kim S.-H., Kim H., Ahn J.-S., Sohn S.-K., Moon J.-H., Jung C.-W., Park S., Lipton J., Kimura S., Jong-Won Kim J.-W., Kim D.
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Journal Title
Leukemia
Volume: epub ahead of print
Issue: 6
Pages: 1439-1450
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Feasibility of the Imatinib Stop Study in the Japanese Clinical Setting: Delightedly Overcome CML Expert Stop TKI Trial (DOMEST Trial).2018
Author(s)
Fujisawa S, Ueda Y, Usuki K, Kobayashi K, Kondo E, Doki N, Nakao T, Kanda Y, Kosugi N, Kosug H, Kumagai T, Harada H, Shikami M, Maeda Y, Sakura T, Inokuchi K, Saito A, Nawa Y, Ogasawara M, Nishida J, Kondo T, Yoshida C, Kuroda H, Tabe Y, Maeda Y, Imajo K, Kojima K, Morita S, Komukai S, Kawaguchi A, Sakamoto J, Kimura S
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Journal Title
International Journal of Clinical Oncology
Volume: 24
Issue: 4
Pages: 445-453
DOI
Related Report
Peer Reviewed
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