Ferritinophagy is a Druggable Vulnerability of Quiescent Leukemic Stem Cells
Larrue, C.; Mouche, S.; Angelino, P.; Sajot, M.; Birsen, R.; Vergez, F.; Recher, C.; Mansat-De Mas, V.; Gu, Q.; Xu, J.; Tsantoulis, P.; Sarry, J.-E.; Tamburini, J.
Show abstract
Acute myeloid leukemia (AML) remains a challenging hematological malignancy with poor prognosis and limited treatment options. Leukemic stem cells (LSCs) contributes to therapeutic failure, post-therapy relapse and adverse outcome. Here, we investigated the role of quiescence and its associated molecular mechanisms in AML pathogenesis and LSCs functions, and identified potential vulnerabilities for therapeutic intervention. We found that LSC-enriched quiescent cell population exhibited a distinct gene set of prognostic significance in AML patients. Furthermore, this quiescent cells subset displayed heightened autophagic activity with a reliance on ferritinophagy, a selective form of autophagy mediated by Nuclear Receptor Coactivator 4 (NCOA4) regulating 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. One Sentence SummaryTargeting quiescent leukemic stem cells via NCOA4-dependent ferritinophagy inhibition may improve therapeutic outcomes in acute myeloid leukemia.
Matching journals
The top 5 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- A novel type of monocytic leukemia stem cell revealed by the clinical use of venetoclax-based therapy 98%
- Extracellular ATP and CD39 activate cAMP-mediated mitochondrial stress response to promote cytarabine resistance in acute myeloid leukemia 98%
- An in vivo CRISPR screening platform for prioritizing therapeutic targets in AML 98%
Similar papers in this journal
- SCD inhibition eradicates AML displaying high de novo fatty acid desaturation and synergizes with chemotherapy 97%
- AML/T cell interactomics uncover correlates of patient outcomes and the key role of ICAM1 in T cell killing of AML 97%
- Resistance to decitabine and 5-azacytidine emerges from adaptive responses of the pyrimidine metabolism network 97%
Similar papers in this journal
- Germline RUNX1 Variation and Predisposition to Childhood Acute Lymphoblastic Leukemia 97%
- CXCL8 secreted by immature granulocytes inhibits wildtype hematopoiesis in chronic myelomonocytic leukemia 96%
- Signatures of immune senescence predict outcomes and define checkpoint blockade-unresponsive microenvironments in acute myeloid leukemia 96%
Similar papers in this journal
- A JAK/STAT-Mediated Inflammatory Signaling Cascade Drives Oncogenesis In AF10-Rearranged AML 98%
- BRG1/BRM inhibitor targets AML stem cells and exerts superior preclinical efficacy combined with BET or Menin inhibitor 98%
- Leukemia escapes immunity by imposing a Type-1 regulatory program on neoantigen-specific CD4+ T cells. 96%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.