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- Fukasawa Kazuya
- Lab. Pharmacol., Dept. Bioactive Molecules, Gifu Pharmaceutical Univ. Lab. Mol. Pharmacol., Inst. Med. Pharmaceut. Health Sci., Kanazawa Univ.
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- Yamada Takanori
- Lab. Pharmacol., Dept. Bioactive Molecules, Gifu Pharmaceutical Univ.
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- Horie Tetsuhiro
- Lab. Pharmacol., Dept. Bioactive Molecules, Gifu Pharmaceutical Univ.
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- Hiraiwa Manami
- Lab. Pharmacol., Dept. Bioactive Molecules, Gifu Pharmaceutical Univ. Lab. Mol. Pharmacol., Inst. Med. Pharmaceut. Health Sci., Kanazawa Univ.
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- Kaneda Katsuyuki
- Lab. Mol. Pharmacol., Inst. Med. Pharmaceut. Health Sci., Kanazawa Univ.
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- Hirao Atsushi
- Div. of Molecular Genetics, Cancer Research Inst., Kanazawa Univ.
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- Hinoi Eiichi
- Lab. Pharmacol., Dept. Bioactive Molecules, Gifu Pharmaceutical Univ.
Bibliographic Information
- Other Title
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- 骨芽細胞のmTORC1はIL-6シグナルを介して急性骨髄性白血病の進展を促進する
Abstract
<p>Although there is increasing evidence that bone forming osteoblasts provide a microenvironment for leukemic stem cells (LSCs) and play a critical role in the maintenance and retention of LSCs, how those cells contribute to leukemia growth remains largely unclear. The mTOR complex 1 (mTORC1), a member of the serine/threonine kinases, is known to regulate the cellular function in various cell types. Using an MLL-AF9 acute myeloid leukemia (AML) mouse model, we found that AML cells enhance the mTORC1 activity in osteoblasts in vivo and in vitro. The osteoblast specific inactivation of Tsc1, a negative regulator of mTORC1, drives differentiation of hematopoietic stem cells (HSCs) toward myeloid lineage during steady state and promotes AML growth. Among the secretory factors examined, interleukine-6 (IL-6) was the most upregulated gene in Tsc1-deficient osteoblasts. Genetic inhibition of IL-6 receptor in AML cells significantly rescued tumor growth in osteoblast specific Tsc1-deficient mice. Collectively, our studies suggest mTORC1/IL-6 axis in osteoblastic niche could be a novel therapeutic target for AML.</p>
Journal
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- Proceedings for Annual Meeting of The Japanese Pharmacological Society
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Proceedings for Annual Meeting of The Japanese Pharmacological Society 93 (0), 1-SS-53-, 2020
Japanese Pharmacological Society
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Keywords
Details 詳細情報について
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- CRID
- 1390283659860034048
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- NII Article ID
- 130007811370
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- ISSN
- 24354953
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- Text Lang
- ja
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- Data Source
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- JaLC
- Crossref
- CiNii Articles
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- Abstract License Flag
- Disallowed