Sökning: (WFRF:(Giustacchini A)) pers:(Neo WH)
> (2017) >
Niche-mediated depl...
Niche-mediated depletion of the normal hematopoietic stem cell reservoir by Flt3-ITD-induced myeloproliferation
-
Mead, AJ (författare)
-
Neo, WH (författare)
-
Barkas, N (författare)
-
visa fler...
-
Matsuoka, S (författare)
-
Giustacchini, A (författare)
-
Facchini, R (författare)
-
Thongjuea, S (författare)
-
Jamieson, L (författare)
-
Booth, CAG (författare)
-
Fordham, N (författare)
-
Di Genua, C (författare)
-
Atkinson, D (författare)
-
Chowdhury, O (författare)
-
Repapi, E (författare)
-
Gray, N (författare)
-
Kharazi, S (författare)
-
Clark, SA (författare)
-
Bouriez, T (författare)
-
- Woll, P (författare)
- Karolinska Institutet
-
Suda, T (författare)
-
Nerlov, C (författare)
-
- Jacobsen, SEW (författare)
- Karolinska Institutet
-
visa färre...
-
(creator_code:org_t)
- 2017-06-21
- 2017
- Engelska.
-
Ingår i: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 214:7, s. 2005-2021
- Relaterad länk:
-
https://rupress.org/...
-
visa fler...
-
http://kipublication...
-
https://doi.org/10.1...
-
visa färre...
Abstract
Ämnesord
Stäng
- Although previous studies suggested that the expression of FMS-like tyrosine kinase 3 (Flt3) initiates downstream of mouse hematopoietic stem cells (HSCs), FLT3 internal tandem duplications (FLT3 ITDs) have recently been suggested to intrinsically suppress HSCs. Herein, single-cell interrogation found Flt3 mRNA expression to be absent in the large majority of phenotypic HSCs, with a strong negative correlation between Flt3 and HSC-associated gene expression. Flt3-ITD knock-in mice showed reduced numbers of phenotypic HSCs, with an even more severe loss of long-term repopulating HSCs, likely reflecting the presence of non-HSCs within the phenotypic HSC compartment. Competitive transplantation experiments established that Flt3-ITD compromises HSCs through an extrinsically mediated mechanism of disrupting HSC-supporting bone marrow stromal cells, with reduced numbers of endothelial and mesenchymal stromal cells showing increased inflammation-associated gene expression. Tumor necrosis factor (TNF), a cell-extrinsic potent negative regulator of HSCs, was overexpressed in bone marrow niche cells from FLT3-ITD mice, and anti-TNF treatment partially rescued the HSC phenotype. These findings, which establish that Flt3-ITD–driven myeloproliferation results in cell-extrinsic suppression of the normal HSC reservoir, are of relevance for several aspects of acute myeloid leukemia biology.
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas
- Av författaren/redakt...
-
Mead, AJ
-
Neo, WH
-
Barkas, N
-
Matsuoka, S
-
Giustacchini, A
-
Facchini, R
-
visa fler...
-
Thongjuea, S
-
Jamieson, L
-
Booth, CAG
-
Fordham, N
-
Di Genua, C
-
Atkinson, D
-
Chowdhury, O
-
Repapi, E
-
Gray, N
-
Kharazi, S
-
Clark, SA
-
Bouriez, T
-
Woll, P
-
Suda, T
-
Nerlov, C
-
Jacobsen, SEW
-
visa färre...
- Artiklar i publikationen
-
The Journal of e ...
- Av lärosätet
-
Karolinska Institutet