Analysis of exacerbation mechanism by KL-6 and MUC1-galectin in multiple myeloma
| Project/Area Number |
18K08374
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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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| Review Section |
Basic Section 54010:Hematology and medical oncology-related
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| Research Institution | Dokkyo Medical University (2019-2020)
Nippon Medical School (2018) |
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Principal Investigator |
Tamura Hideto 獨協医科大学, 医学部, 教授 (70256949)
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| Co-Investigator(Kenkyū-buntansha) |
石橋 真理子 日本医科大学, 医学部, 助教 (20599047)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 多発性骨髄腫 / KL-6 / 予後不良因子 / MUC1 / galectin-3 |
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| Outline of Final Research Achievements |
The purpose of this study was to determine the function of KL-6, a sialylated carbohydrate glycoprotein present in human MUC1 mucin, in the pathophysiology of multiple myeloma (MM). In the analysis of newly diagnosed MM patients, those with high levels of KL-6 (n=22) had lower hemoglobin and higher LDH levels and significantly shorter progression-free survival time compared with the normal-level group (n=173). Next, we established a KL-6-producing cell line from a refractory, rapidly progressing MM patient. It exhibited complex karyotypes including the 1q21+, CD28+CD229+ phenotype and high proliferative potential but the same sensitivity to anti-myeloma drugs as other MM cell lines.
Those results suggest that KL-6 is directly associated with MM disease progression. Further studies are underway to clarify the related gene expression and mechanisms of proliferation potential.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究により、新規MM患者の約10%が示す血清KL-6高値の臨床的意義が明らかとなり、血清KL-6が予後の予測、治療の選択に役立つことが示唆された。また、MM細胞におけるKL-6産生とMUC1 mRNAと細胞膜タンパク発現、MUC1遺伝子多型などとの関連が解明され、本研究の学術的意義が示された。さらに、MMにおけるKL-6は腫瘍細胞増殖に重要な役割を果たしており、Gal-3ーMUC1-KL-6相互作用が、形質細胞白血病進展に関与する可能性があり、KL-6を標的とした新規治療法の開発が期待された。
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Report
(4 results)
Research Products
(2 results)
