Myeloma cells are activated in bone marrow microenvironment by the CD180/MD-1 complex, which senses lipopolysaccharide.

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K09937
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Jichi Medical University
• Principal Investigator: Kikuchi Jiro 自治医科大学, 医学部, 准教授 (60371035)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 多発性骨髄腫 / Toll様受容体 / 骨髄微小環境

Outline of Final Research Achievements

Multiple myeloma (MM) is one of the most intractable malignancies characterized by the infiltration and growth of malignant plasma cells in the bone marrow. Elucidation of the mechanisms underlying cell adhesion-mediated drug resistance may prolong remission and ultimately improve the survival of MM patients. We found that CD180, a non-canonical LPS receptor, was markedly up-regulated in marrow microenvironment. Bacterial LPS enhanced the growth of MM cells in positive correlation with the expression levels of CD180 in vitro and in vivo. Promoter analyses identified IKZF1 as a pivotal transcriptional activator of the CD180 gene. Immunomodulatory drugs (IMiDs) could prevent the LPS-triggered activation of myeloma cells by targeting CD180. Taken together, IMiDs prevented the infection-triggered disease progression via inhibition of CD180 expression and would be effective for prolonging survival in MM patients.

Free Research Field

血液腫瘍学

Academic Significance and Societal Importance of the Research Achievements

本研究は、病態の進展に与える感染の影響や、その機序におけるCD180の役割を明らかにした初めての報告である。また、CD180発現の阻害に働く免疫調節薬が感染に伴う病態の進展の予防にも有効となる可能性を示す等、臨床的に意義のある研究内容と言える。