Myeloma cells are activated in bone marrow microenvironment by the CD180/MD-1 complex, which senses lipopolysaccharide.
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
|
Project Status |
Completed (Fiscal Year 2019)
|
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)
|
Keywords | 多発性骨髄腫 / Toll様受容体 / 骨髄微小環境 / CD180 / 感染 / 血液内科学 / 血液腫瘍学 |
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.
|
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。
|
Report
(4 results)
Research Products
(20 results)
-
[Journal Article] Soluble SLAMF7 Promotes the Growth of Myeloma Cells via Homophilic Interaction with Surface SLAMF7.2020
Author(s)
Kikuchi J, Hori M, Iha H, Toyama-Sorimachi N, Hagiwara S, Kuroda Y, Koyama D, Izumi T, Yasui H, Suzuki A, Furukawa Y.
-
Journal Title
Leukemia.
Volume: 34
Issue: 1
Pages: 180-195
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
[Journal Article] Eradication of central nervous system leukemia of T-cell origin with a brain-permeable LSD1 inhibitor.2019
Author(s)
Saito S, Kikuchi J, Koyama D, Sato S, Koyama H, Osada N, Kuroda Y, Akahane K, Inukai T, Umehara T, Furukawa Y.
-
Journal Title
Clin Cancer Res
Volume: 25
Issue: 5
Pages: 1601-1611
DOI
Related Report
Peer Reviewed
-
-
-
-
-
[Journal Article] Anti-leukemic activity of bortezomib and carfilzomib on B-cell precursor ALL with IKZF1 deletion.2017
Author(s)
Takahashi K, Inukai T, Imamura T, Yano M, , Nemoto A, Sato H, Huang M, Abe M, Kagami K, Shinohara T, Watanabe A, Somazu S, Oshiro H, Akahane K, Goi K, Kikuchi J, Furukawa Y, Goto H, Minegishi M, Iwamoto S, Sugita K.
-
Journal Title
PLoS One
Volume: 12
Issue: 12
Pages: e0188680-e0188680
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
-
-
-
[Presentation] Jiro Kikuchi, Shiori Saito, Daisuke Koyama, Shin Sato, Hiroo Koyama, Naoki Osada, Yoshiaki Kuroda, Koshi Akahane, Takeshi Inukai, Takashi Umehara, Yusuke Furukawa2018
-
-
-
-
-
-