mTORC1 in osteoblastic niche regulates progression of acute myeloid leukemia.

Fukasawa Kazuya, Horie Tetsuhiro, Hiraiwa Manami, Yamada Takanori, Iezaki Takashi, Kaneda Katsuyuki, Hirao Atsushi, Hinoi Eiichi

doi:10.1254/jpssuppl.92.0_1-ss-47

Bibliographic Information

Other Title

骨芽細胞による白血病進展制御機構の解明研究

Abstract

<p>Hematopoieticstem cells(HSCs) and leukemic stem cells(LSCs) have self-renewal ability to maintain normal hematopoiesis and leukemia propagation, respectively. Recently, it has been reported that bone forming osteoblasts provide a microenvironment for LSCs and are implicated in pathogenesis and progression of leukemia as an osteoblastic niche in bone marrow. The mTOR complex 1 (mTORC1), a member of the serine/threonine kinases, is known to regulate the cellular function in various cell types. Although the role of osteoblastic mTORC1 on bone mass accrual has been investigated, here we show a critical role of mTORC1 in regulating normal hematopoiesis and leukemia progression through its expression in osteoblasts in mice. Using a mouse models of acute myeloid leukemia (AML), we revealed that AML cells enhance the mTORC1 activity in osteoblasts in vivo and in vitro. Subsequent analyses determined that inactivation of Tsc1, a negative regulator of mTORC1, in osteoblasts results in a marked acceleration of AML. These findings highlight a critical role of mTORC1 in normal hematopoiesis and leukemia propagation, at least in part, through its expression in osteoblastic niche.</p>

Journal

Proceedings for Annual Meeting of The Japanese Pharmacological Society

Proceedings for Annual Meeting of The Japanese Pharmacological Society 92 (0), 1-SS-47-, 2019

Japanese Pharmacological Society

Details 詳細情報について

CRID: 1390002184884316928

NII Article ID: 130007812833

DOI: 10.1254/jpssuppl.92.0_1-ss-47

ISSN: 24354953

Web Site: https://www.jstage.jst.go.jp/article/jpssuppl/92/0/92_1-SS-47/_pdf

Text Lang: ja

Data Source

JaLC
Crossref
CiNii Articles

Abstract License Flag: Disallowed

Export