| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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)
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| 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.
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