Publications by authors named "Mathilde Gotanegre"
Unlabelled: Identifying mechanisms underlying relapse is a major clinical issue for effective cancer treatment. The emerging understanding of the importance of metastasis in hematologic malignancies suggests that it could also play a role in drug resistance and relapse in acute myeloid leukemia (AML). In a cohort of 1,273 AML patients, we uncovered that the multifunctional scavenger receptor CD36 was positively associated with extramedullary dissemination of leukemic blasts, increased risk of relapse after intensive chemotherapy, and reduced event-free and overall survival.
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- Recent advances in targeted therapies for acute myeloid leukemia (AML) have not significantly addressed many cases, especially those lacking actionable therapy targets.
- In a study of 127 AML cases, 40% showed alterations in RAS pathway genes, which correlated with worse outcomes and survival rates for patients.
- The combination of the MEK inhibitor trametinib and the anti-helminthic drug pyrvinium pamoate showed promising antileukemic effects in both laboratory tests and mouse models, suggesting a potential new treatment strategy for RAS+ AML.
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- Therapy resistance is a big issue in treating acute myeloid leukemia (AML), and researchers have created a 'MitoScore' to identify patients with high oxidative phosphorylation in their cells.
- AML cells that resist treatment with cytarabine (AraC) show reliance on certain mitochondrial proteins and respond well to a combination of venetoclax (VEN) and AraC, but not to VEN with azacytidine.
- Further research found that resistant AML cells adapt by altering their mitochondrial functions, and targeting these adaptations could improve treatment outcomes, suggesting a potential strategy to alternate between VEN therapies based on MitoScore levels to boost effectiveness.
Mutations in IDH induce epigenetic and transcriptional reprogramming, differentiation bias, and susceptibility to mitochondrial inhibitors in cancer cells. Here, we first show that cell lines, PDXs, and patients with acute myeloid leukemia (AML) harboring an IDH mutation displayed an enhanced mitochondrial oxidative metabolism. Along with an increase in TCA cycle intermediates, this AML-specific metabolic behavior mechanistically occurred through the increase in electron transport chain complex I activity, mitochondrial respiration, and methylation-driven CEBPα-induced fatty acid β-oxidation of IDH1 mutant cells.
View Article and Find Full Text PDFDrug tolerant/resistant leukemic stem cell (LSC) subpopulations may explain frequent relapses in acute myeloid leukemia (AML), suggesting that these relapse-initiating cells (RICs) persistent after chemotherapy represent bona fide targets to prevent drug resistance and relapse. We uncover that calcitonin receptor-like receptor (CALCRL) is expressed in RICs, and that the overexpression of CALCRL and/or of its ligand adrenomedullin (ADM), and not CGRP, correlates to adverse outcome in AML. CALCRL knockdown impairs leukemic growth, decreases LSC frequency, and sensitizes to cytarabine in patient-derived xenograft models.
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- * In AML, early cell death from APR-246 is linked to a process called ferroptosis, which is characterized by oxidative damage and can be inhibited by substances like iron chelators and antioxidants.
- * The ability of AML cells to counteract the effects of lipid peroxides through increased uptake of cystine plays a significant role in their response to APR-246, with evidence showing that combining APR-246 with other therapies enhances cell death.
Relapses driven by chemoresistant leukemic cell populations are the main cause of mortality for patients with acute myeloid leukemia (AML). Here, we show that the ectonucleotidase CD39 (ENTPD1) is upregulated in cytarabine-resistant leukemic cells from both AML cell lines and patient samples and . CD39 cell-surface expression and activity is increased in patients with AML upon chemotherapy compared with diagnosis, and enrichment in CD39-expressing blasts is a marker of adverse prognosis in the clinics.
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- Resistance to acute myeloid leukemia (AML) treatment is common, highlighting the need to understand the mechanisms behind it.
- The study shows that inhibiting the deubiquitinylase USP7 can significantly reduce AML cell growth, disrupt DNA replication, and increase cell death, suggesting USP7 plays a critical role in drug resistance.
- A gene signature linked to USP7 is found to be more prevalent in AML relapse cases and enhances the effectiveness of cytarabine, making USP7 a promising target for overcoming treatment resistance in AML.
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- The study highlights the significance of CDC25A phosphatase in the proliferation and differentiation of acute myeloid leukemia (AML) with the FLT3-ITD mutation.
- It demonstrates that the levels of CDC25A are regulated by a connected pathway involving STAT5 and miR-16, with STAT5 activating CDC25A transcription and FLT3-ITD inhibiting miR-16 expression.
- The findings suggest that manipulating miR-16 levels can influence CDC25A expression and impact the proliferation and differentiation of AML cells, pointing to a crucial FLT3-ITD/STAT5/miR-16/CDC25A interaction in AML progression.
Chemotherapies alter cellular redox balance and reactive oxygen species (ROS) content. Recent studies have reported that chemoresistant cells have an increased oxidative state in hematologic malignancies. In this study, we demonstrated that chemoresistant acute myeloid leukemia (AML) cells had a lower level of mitochondrial and cytosolic ROS in response to cytarabine (AraC) and overexpressed myeloperoxidase (MPO), a heme protein that converts hydrogen peroxide to hypochlorous acid (HOCl), compared with sensitive AML cells.
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