Imperial College London
Alternate

ProfessorCristinaLo Celso

Faculty of Natural Sciences, Department of Life Sciences

Co-Director Centre for Haematology & Prof Stem Cell Biology
 
 
 
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Contact

 

c.lo-celso

 
 
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Location

 

548Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Lo:2017:10.1016/j.stem.2017.11.006,
author = {Lo, Celso C and Hawkins, ED and Akinduro, O and Duarte, D and Ang, H and De, Filippo K and Kong, I and Haltalli, M and Ruivo, N and Straszkowski, L and Vervoort, S and McLean, C and Weber, TS and Khorshed, R and Pirillo, C and Wei, A and Ramasamy, SK and Kusumbe, AP and Duffy, K and Adams, RH and Purton, LP and Carlin, LM},
doi = {10.1016/j.stem.2017.11.006},
journal = {Cell Stem Cell},
pages = {64--77.e6},
title = {Inhibition of endosteal vascular niche remodeling rescues hematopoietic stem cell loss in AML},
url = {http://dx.doi.org/10.1016/j.stem.2017.11.006},
volume = {22},
year = {2017}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Bone marrow vascular niches sustain hematopoietic stem cells (HSCs) and are drastically remodeled in leukemia to support pathological functions. Acute myeloid leukemia (AML) cells produce angiogenic factors, which likely contribute to this remodeling, but anti-angiogenic therapies do not improve AML patient outcomes. Using intravital microscopy, we found that AML progression leads to differential remodeling of vasculature in central and endosteal bone marrow regions. Endosteal AML cells produce pro-inflammatory and anti-angiogenic cytokines and gradually degrade endosteal endothelium, stromal cells, and osteoblastic cells, whereas central marrow remains vascularized and splenic vascular niches expand. Remodeled endosteal regions have reduced capacity to support non-leukemic HSCs, correlating with loss of normal hematopoiesis. Preserving endosteal endothelium with the small molecule deferoxamine or a genetic approach rescues HSCs loss, promotes chemotherapeutic efficacy, and enhances survival. These findings suggest that preventing degradation of the endosteal vasculature may improve current paradigms for treating AML.
AU  - Lo,Celso C
AU  - Hawkins,ED
AU  - Akinduro,O
AU  - Duarte,D
AU  - Ang,H
AU  - De,Filippo K
AU  - Kong,I
AU  - Haltalli,M
AU  - Ruivo,N
AU  - Straszkowski,L
AU  - Vervoort,S
AU  - McLean,C
AU  - Weber,TS
AU  - Khorshed,R
AU  - Pirillo,C
AU  - Wei,A
AU  - Ramasamy,SK
AU  - Kusumbe,AP
AU  - Duffy,K
AU  - Adams,RH
AU  - Purton,LP
AU  - Carlin,LM
DO  - 10.1016/j.stem.2017.11.006
EP  - 77
PY  - 2017///
SN  - 1875-9777
SP  - 64
TI  - Inhibition of endosteal vascular niche remodeling rescues hematopoietic stem cell loss in AML
T2  - Cell Stem Cell
UR  - http://dx.doi.org/10.1016/j.stem.2017.11.006
UR  - https://www.sciencedirect.com/science/article/pii/S1934590917304587?via%3Dihub
UR  - http://hdl.handle.net/10044/1/53606
VL  - 22
ER  -
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