NDLI: mTOR signaling is activated by FLT3 kinase and promotes survival of FLT3- mutated acute myeloid leukemia cells

Content Provider	Springer Nature : BioMed Central
Author	Chen, Weina Drakos, Elias Grammatikakis, Ioannis Schlette, Ellen J Li, Jiang Leventaki, Vasiliki Staikou-Drakopoulou, Efi Patsouris, Efstratios Panayiotidis, Panayiotis Medeiros, L Jeffrey Rassidakis, George Z
Abstract	Activating mutations of the FLT3 gene mediate leukemogenesis, at least in part, through activation of PI3K/AKT. The mammalian target of rapamycin (mTOR)-Raptor signaling pathway is known to act downstream of AKT. Here we show that the mTOR effectors, 4EBP1, p70S6K and rpS6, are highly activated in cultured and primary FLT3-mutated acute myeloid leukemia (AML) cells. Introduction of FLT3-ITD expressing constitutively activated FLT3 kinase further activates mTOR and its downstream effectors in BaF3 cells. We also found that mTOR signaling contributes to tumor cell survival, as demonstrated by pharmacologic inhibition of PI3K/AKT/mTOR, or total silencing of the mTOR gene. Furthermore, inhibition of FLT3 kinase results in downregulation of mTOR signaling associated with decreased survival of FLT3-mutated AML cells. These findings suggest that mTOR signaling operates downstream of activated FLT3 kinase thus contributing to tumor cell survival, and may represent a promising therapeutic target for AML patients with mutated-FLT3.
Related Links	https://molecular-cancer.biomedcentral.com/counter/pdf/10.1186/1476-4598-9-292.pdf
Ending Page	7
Page Count	7
Starting Page	1
File Format	HTM / HTML
ISSN	14764598
DOI	10.1186/1476-4598-9-292
Journal	Molecular Cancer
Issue Number	1
Volume Number	9
Language	English
Publisher	BioMed Central
Publisher Date	2010-11-10
Access Restriction	Open
Subject Keyword	Cancer Research Oncology Acute Myeloid Leukemia Rapamycin Acute Myeloid Leukemia Patient mTOR Signaling Acute Myeloid Leukemia Cell
Content Type	Text
Resource Type	Article
Subject	Oncology Molecular Medicine Cancer Research
Journal Impact Factor	27.7/2023
5-Year Journal Impact Factor	31.3/2023

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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