Pathophysiological role of inflammatory chemokine, CCL3, in chronic myeloid leukemia
| Project/Area Number |
16K08733
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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 |
Experimental pathology
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| Research Institution | Kanazawa University |
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Principal Investigator |
BABA Tomohisa 金沢大学, がん進展制御研究所, 准教授 (00452095)
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| Research Collaborator |
Mukaida Naofumi
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 慢性骨髄性白血病 / 白血病幹細胞 / 造血幹細胞 / 炎症性ケモカイン / 細胞間競合拮抗 / ケモカイン |
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| Outline of Final Research Achievements |
Basophilia is a frequently observed hematological abnormality in chronic myeloid leukemia (CML), but its pathophysiological roles are undefined. In this study, we demonstrated that basophil-like leukemia cells proliferate and constitutively express an inflammatory chemokine, CCL3, in the bone marrow of mice developing CML. Moreover, CCL3 preferentially inhibits the proliferation of normal hematopoietic stem/progenitor cells, thereby facilitating the dominant proliferation of leukemia stem cells during the initiation process of CML development. We further demonstrated that the depletion of basophil-like leukemia cells or the oral-administration of CCL3 inhibitor efficiently prevented the CML development.
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| Academic Significance and Societal Importance of the Research Achievements |
CMLの原因遺伝子である、BCR-ABLに対するチロシンキナーゼ阻害薬（TKI）の開発により、CML患者の生命予後が劇的に改善されている。しかしながら、TKI抵抗性を示す、白血病幹細胞が治療後も残存し、再発の原因となっていることが知られている。本研究で得られた知見を基盤として、正常造血細胞と白血病幹細胞の競合的相互作用を標的とした治療戦略の確立による、CMLの根治を目的とした新たな治療法の開発が期待できる。
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Report
(4 results)
Research Products
(16 results)
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[Journal Article] Alveolar macrophages drive hepatocellular carcinoma lung metastasis by generating leukotriene B4.2018
Author(s)
Nosaka T, Baba T, Tanabe Y, Sasaki S, Nishimura T, Imamura Y, Yurino H, Hashimoto S, Arita M, Nakamoto Y, Mukaida N.
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Journal Title
J Immunol.
Volume: 200
Pages: 1839-1852
DOI
Related Report
Peer Reviewed / Open Access
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