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Differential Reponses of Hematopoietic Stem and Progenitor Cells to mTOR Inhibition
Joint Authors
LaRue, Amanda C.
Yang, Aimin
Xiao, Xia
Zhao, Mingfeng
Schulte, Bradley A.
Wang, Gavin Y.
Source
Issue
Vol. 2015, Issue 2015 (31 Dec. 2015), pp.1-9, 9 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2015-06-28
Country of Publication
Egypt
No. of Pages
9
Abstract EN
Abnormal activation of the mammalian target of rapamycin (mTOR) signaling pathway has been observed in a variety of human cancers.
Therefore, targeting of the mTOR pathway is an attractive strategy for cancer treatment and several mTOR inhibitors, including AZD8055 (AZD), a novel dual mTORC1/2 inhibitor, are currently in clinical trials.
Although bone marrow (BM) suppression is one of the primary side effects of anticancer drugs, it is not known if pharmacological inhibition of dual mTORC1/2 affects BM hematopoietic stem and progenitor cells (HSPCs) function and plasticity.
Here we report that dual inhibition of mTORC1/2 by AZD or its analogue (KU-63794) depletes mouse BM Lin−Sca-1+c-Kit+ cells in cultures via the induction of apoptotic cell death.
Subsequent colony-forming unit (CFU) assays revealed that inhibition of mTORC1/2 suppresses the clonogenic function of hematopoietic progenitor cells (HPCs) in a dose-dependent manner.
Surprisingly, we found that dual inhibition of mTORC1/2 markedly inhibits the growth of day-14 cobblestone area-forming cells (CAFCs) but enhances the generation of day-35 CAFCs.
Given the fact that day-14 and day-35 CAFCs are functional surrogates of HPCs and hematopoietic stem cells (HSCs), respectively, these results suggest that dual inhibition of mTORC1/2 may have distinct effects on HPCs versus HSCs.
American Psychological Association (APA)
Yang, Aimin& Xiao, Xia& Zhao, Mingfeng& LaRue, Amanda C.& Schulte, Bradley A.& Wang, Gavin Y.. 2015. Differential Reponses of Hematopoietic Stem and Progenitor Cells to mTOR Inhibition. Stem Cells International،Vol. 2015, no. 2015, pp.1-9.
https://search.emarefa.net/detail/BIM-1076271
Modern Language Association (MLA)
Yang, Aimin…[et al.]. Differential Reponses of Hematopoietic Stem and Progenitor Cells to mTOR Inhibition. Stem Cells International No. 2015 (2015), pp.1-9.
https://search.emarefa.net/detail/BIM-1076271
American Medical Association (AMA)
Yang, Aimin& Xiao, Xia& Zhao, Mingfeng& LaRue, Amanda C.& Schulte, Bradley A.& Wang, Gavin Y.. Differential Reponses of Hematopoietic Stem and Progenitor Cells to mTOR Inhibition. Stem Cells International. 2015. Vol. 2015, no. 2015, pp.1-9.
https://search.emarefa.net/detail/BIM-1076271
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1076271