Analysis of exacerbation mechanism by KL-6 and MUC1-galectin in multiple myeloma

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08374
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Dokkyo Medical University (2019-2020); Nippon Medical School (2018)
• Principal Investigator: Tamura Hideto 獨協医科大学, 医学部, 教授 (70256949)
• Co-Investigator(Kenkyū-buntansha): 石橋 真理子 日本医科大学, 医学部, 助教 (20599047)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 多発性骨髄腫 / KL-6 / 予後不良因子 / MUC1

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.

Free Research Field

血液腫瘍学

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。