Elucidation of the function of exhaustion-related molecules in human leukemic stem cells
Project/Area Number |
16H06250
|
Research Category |
Grant-in-Aid for Young Scientists (A)
|
Allocation Type | Single-year Grants |
Research Field |
Hematology
|
Research Institution | Kyushu University |
Principal Investigator |
|
Project Period (FY) |
2016-04-01 – 2019-03-31
|
Project Status |
Completed (Fiscal Year 2018)
|
Budget Amount *help |
¥24,050,000 (Direct Cost: ¥18,500,000、Indirect Cost: ¥5,550,000)
Fiscal Year 2018: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
Fiscal Year 2017: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
Fiscal Year 2016: ¥8,450,000 (Direct Cost: ¥6,500,000、Indirect Cost: ¥1,950,000)
|
Keywords | TIM-3 / 白血病幹細胞 / Want pathway / TIM-3分子 / 癌 |
Outline of Final Research Achievements |
In the present study, we tried to clarify the function of TIM-3 signaling in human acute myeloid leukemia stem cells. TIM-3 has been originally identified as a T-cell exhaustion marker; however, its function and signaling in leukemic stem cells are still elusive. We identified that galectin-9, a ligand for TIM-3, ligation to TIM-3 recruits HCK to its cytoplasmic tail and HCK is subsequently activated in leukemic stem cells, leading to the activation of canonical Wnt pathway through the interaction with p-120 catenin even in the absence of Wnt ligands. TIM-3 signaling directly activates the canonical Wnt pathway and induces the aberrant beta-catenin accumulation independent of conventional Wnt ligands. Thus, TIM-3 signaling is a novel and specific canonical Wnt pathway regulator in human leukemic stem cells.
|
Academic Significance and Societal Importance of the Research Achievements |
Canonical Wnt pathway関連遺伝子変異によるβカテニン活性化機構が多くの固形腫瘍では知られている一方で、ヒト急性骨髄性白血病においてはそのような遺伝子変異が認められないことから全く異なるメカニズムでβカテニン活性化が生じていると考えられてきたが詳細は不明であった。本研究により、白血病幹細胞特異的分子であるTIM-3シグナルとその下流の分子群がCanonical Wnt pathwayを直接活性化する新しい分子機構であることを見出した。すなわち、ヒト急性骨髄性白血病における遺伝子変異非依存的βカテニン活性化機構としてTIM-3シグナルとその下流分子群の同定に至った。
|
Report
(4 results)
Research Products
(14 results)
-
-
[Journal Article] Human herpes virus-6-associated encephalitis/myelitis mimicking calcineurin inhibitor induced pain syndrome in allogeneic stem cell transplantation recipients.2018
Author(s)
Yoshimoto G, Mori Y, Kato K, Shima T, Miyawaki K, Kikushige Y, Kamezaki K, Numata A, Maeda T, Takenaka K, Iwasaki H, Teshima T, Akashi K, Miyamoto T
-
Journal Title
Biol Blood Marrow Transplant
Volume: 24
Issue: 12
Pages: 2540-2548
DOI
Related Report
Peer Reviewed
-
[Journal Article] E-cadherin regulates proliferation of colorectal cancer stem cells through NANOG.2018
Author(s)
Tamura S, Isobe T, Ariyama H, Nakano M, Kikushige Y, Takaishi S, Kusaba H, Takenaka K, Ueki T, Nakamura M, Akashi K, Baba E.
-
Journal Title
Oncology Reports
Volume: 40 (2)
Pages: 693-703
DOI
Related Report
Peer Reviewed / Open Access
-
[Journal Article] Identification of unipotent megakaryocyte progenitors in human hematopoiesis.2017
Author(s)
K. Miyawaki. Iwasaki, T. Jiromaru, H. Kusumoto, A. Yurino, T. Sugio, Y. Uehara, J. Odawara, S. Daitoku, Y. Kunisaki, Y. Mori, Y. Arinobu, H. Tsuzuki, Y. Kikushige, T. Iino, K. Kato, K. Takenaka, T. Miyamoto, T. Maeda, *K. Akashi
-
Journal Title
Blood
Volume: 印刷中
Issue: 25
Pages: 3332-3343
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
-
[Journal Article] Mobilization of human immature hematopoietic progenitors through combinatory use of bortezomib and immunomodulatory drugs.2017
Author(s)
T. Tochigi, T. Aoki, *Y. Kikushige, T. Kamimura, Y. Ito, T. Shima, T. Yamauchi, Y. Mori, G. Yoshimoto, K. Kamezaki, K. Kato, K. Takenaka, H. Iwasaki, K. Akashi, T. Miyamoto
-
Journal Title
Int J Hematol
Volume: 105
Issue: 4
Pages: 423-432
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
-
[Journal Article] Enhanced Reconstitution of Human Erythropoiesis and Thrombopoiesis in an Immunodeficient Mouse Model with Kit(Wv) Mutations.2016
Author(s)
A. Yurino, K. Takenaka, T. Yamauchi, T. Nunomura, Y. Uehara, F. Jinnouchi, K. Miyawaki, Y. Kikushige, K. Kato, T. Miyamoto, H. Iwasaki, Y. Kunisaki, *K. Akashi
-
Journal Title
Stem Cell Reports
Volume: 7
Issue: 3
Pages: 425-438
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
-
-
-
-
-
-
-
-