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| Status |
Public on Nov 01, 2017 |
| Title |
Selective endosteal remodeling of blood vessels in acute myeloid leukemia promotes malignancy at the expense of hematopoietic stem cells |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Hematopoietic stem cell (HSC) function requires bone marrow vascular niches, which have been proposed to be co-opted by leukemia cells to support their propagation. Acute myeloid leukemia (AML) cells produce angiogenic factors; however, anti-angiogenic therapies have not improved AML patient outcome. Using intravital microscopy we uncovered hierarchical vascular remodeling with AML progression. AML cells outcompete non-malignant hematopoiesis by gradual elimination of stroma cells, endosteal endothelium, and osteoblastic cells. While central marrow remains vascularized and splenic vascular niches expand, the remodeled endosteal regions lose the ability to retain HSCs. Overall, the endosteal endothelium microenvironment is altered by AML, yet by preserving it we rescue HSC loss and promote chemotherapeutic efficacy. Our findings suggest therapies targeting the endosteal vasculature may improve existing AML therapeutic regimes.
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| |
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| Overall design |
RNA-Seq analysis on different AML clones versus HSC controls
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| |
|
| Contributor(s) |
Duarte D |
| Citation(s) |
29276143 |
| |
| Submission date |
Oct 19, 2017 |
| Last update date |
May 15, 2019 |
| Contact name |
Isabella Kong |
| Organization name |
The Walter and Eliza Hall Institute of Medical Research
|
| Street address |
1G Royal Parade
|
| City |
Parkville |
| State/province |
VIC |
| ZIP/Postal code |
3052 |
| Country |
Australia |
| |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
|
| Samples (27)
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| Relations |
| BioProject |
PRJNA414975 |
| SRA |
SRP120494 |
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