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| Status |
Public on Jun 16, 2024 |
| Title |
Ferritinophagy is a Druggable Vulnerability of Quiescent Leukemic Stem Cells [scRNA-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Acute myeloid leukemia (AML) remains a challenging hematological malignancy with poor prognosis and limited treatment options. Post-therapy relapse, particularly driven by leukemic stem cells (LSCs), contributes to therapeutic failure and adverse outcome. Here, we investigated the role of quiescence and its associated molecular mechanisms in AML pathogenesis and identified potential vulnerabilities for therapeutic intervention. We found that quiescent AML cells, enriched for LSC functions, exhibited a distinct gene set that served as a significant prognostic factor for poor outcomes in AML patients. Furthermore, quiescent cells displayed heightened autophagic activity, with a reliance on ferritinophagy, a selective form of autophagy mediated by Nuclear Receptor Coactivator 4 (NCOA4), for iron bioavailability. Inhibition of NCOA4 genetically or chemically showed potent anti-leukemic effects, particularly targeting the LSC compartment. These findings uncover that ferritinophagy inhibition may represent a promising therapeutic strategy for patients with AML.
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| Overall design |
Two PDX AML samples (TUH84 and TUH102) were analyzed seven days after xenotransplantation in vivo in immunodeficient mice.
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| Contributor(s) |
Larrue C, Tamburini J |
| Citation(s) |
39047119 |
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| Submission date |
Jun 15, 2023 |
| Last update date |
Sep 16, 2024 |
| Contact name |
Jerome Tamburini |
| E-mail(s) |
jerome.tamburinibonnefoy@unige.ch
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| Organization name |
Cochin Institute
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| Lab |
jerome tamburini
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| Street address |
22 rue mechain
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| City |
paris |
| State/province |
N/A |
| ZIP/Postal code |
75014 |
| Country |
France |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (2) |
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| This SubSeries is part of SuperSeries: |
| GSE235070 |
Ferritinophagy is a Druggable Vulnerability of Quiescent Leukemic Stem Cells |
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| Relations |
| BioProject |
PRJNA984274 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE235058_RAW.tar |
38.1 Mb |
(http)(custom) |
TAR (of MTX, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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