Mathilde Gotanègre
A5074996222- Histone Deacetylase Inhibitors Research
- Acute Myeloid Leukemia Research
- Protein Degradation and Inhibitors
- Peptidase Inhibition and Analysis
- Lung Cancer Research Studies
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- MicroRNA in disease regulation
- Immune cells in cancer
- GDF15 and Related Biomarkers
- Epigenetics and DNA Methylation
- Chronic Myeloid Leukemia Treatments
- Adenosine and Purinergic Signaling
- Receptor Mechanisms and Signaling
- Glutathione Transferases and Polymorphisms
- Signaling Pathways in Disease
- Chemokine receptors and signaling
- PI3K/AKT/mTOR signaling in cancer
- Retinoids in leukemia and cellular processes
- Neuroblastoma Research and Treatments
- Quinazolinone synthesis and applications
- DNA Repair Mechanisms
- Drug Transport and Resistance Mechanisms
- Cancer, Hypoxia, and Metabolism
- Ubiquitin and proteasome pathways
- Mitochondrial Function and Pathology
Centre de Recherche en Cancérologie de Toulouse
2018-2023
Inserm
2019-2023
Centre National de la Recherche Scientifique
2019-2023
Université de Toulouse
2019-2023
La Ligue Contre le Cancer
2020-2023
ideXlab (France)
2021-2023
Université Toulouse III - Paul Sabatier
2018-2021
APR-246 is a promising new therapeutic agent that targets p53 mutated proteins in myelodysplastic syndromes and acute myeloid leukemia (AML). reactivates the transcriptional activity of mutants by facilitating their binding to DNA target sites. Recent studies solid cancers have found can also induce p53-independent cell death. In this study, we demonstrate AML death occurring early after exposure suppressed iron chelators, lipophilic antioxidants inhibitors lipid peroxidation, correlates...
Mutations in IDH induce epigenetic and transcriptional reprogramming, differentiation bias, susceptibility to mitochondrial inhibitors cancer cells. Here, we first show that cell lines, PDXs, patients with acute myeloid leukemia (AML) harboring an mutation displayed enhanced oxidative metabolism. Along increase TCA cycle intermediates, this AML-specific metabolic behavior mechanistically occurred through the electron transport chain complex I activity, respiration, methylation-driven...
Identifying mechanisms underlying relapse is a major clinical issue for effective cancer treatment. The emerging understanding of the importance metastasis in hematologic malignancies suggests that it could also play role drug resistance and acute myeloid leukemia (AML). In cohort 1,273 AML patients, we uncovered multifunctional scavenger receptor CD36 was positively associated with extramedullary dissemination leukemic blasts, increased risk after intensive chemotherapy, reduced event-free...
Chemotherapies alter cellular redox balance and reactive oxygen species (ROS) content. Recent studies have reported that chemoresistant cells an increased oxidative state in hematologic malignancies. In this study, we demonstrated acute myeloid leukemia (AML) had a lower level of mitochondrial cytosolic ROS response to cytarabine (AraC) overexpressed myeloperoxidase (MPO), heme protein converts hydrogen peroxide hypochlorous acid (HOCl), compared with sensitive AML cells. High MPO-expressing...
Relapses driven by chemoresistant leukemic cell populations are the main cause of mortality for patients with acute myeloid leukemia (AML). Here, we show that ectonucleotidase CD39 (ENTPD1) is upregulated in cytarabine-resistant cells from both AML lines and patient samples vivo vitro. cell-surface expression activity increased upon chemotherapy compared diagnosis, enrichment CD39-expressing blasts a marker adverse prognosis clinics. High promotes cytarabine resistance enhancing...
Abstract Drug 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 calcitonin receptor-like receptor (CALCRL) is expressed RICs, the overexpression of CALCRL and/or its ligand adrenomedullin (ADM), not CGRP, correlates adverse outcome AML. knockdown impairs...
Despite recent advances in acute myeloid leukemia (AML) molecular characterization and targeted therapies, a majority of AML cases still lack therapeutically actionable targets. In 127 with unmet therapeutic needs, as defined by the exclusion ELN favorable FLT3-ITD mutations, we identified 51 (40%) alterations RAS pathway genes (RAS+, mostly NF1, NRAS, KRAS, PTPN11 genes). 79 homogeneously treated patients from this cohort, RAS+ status were associated higher white blood cell count, LDH,...
Abstract We recently identified the CDC25A phosphatase as a key actor in proliferation and differentiation acute myeloid leukemia expressing FLT3-ITD mutation. In this paper we demonstrate that level is controlled by complex STAT5/miR-16 transcription translation pathway working downstream of receptor. First, established CHIP analysis STAT5 directly involved FLT3-ITD-dependent gene transcription. addition, determined miR-16 expression repressed activity, participates repression. accordance...
Abstract The development of resistance to conventional and targeted therapy represents a major clinical barrier in treatment acute myeloid leukemia (AML). We show that the cytarabine (AraC) its associated mitochondrial phenotype were reversed by genetic silencing or pharmacological inhibition BCL2 caspase-dependent manner. BCL2-inhibitor venetoclax (VEN) enhancement AraC efficacy was independent differentiation phenotype, characteristic response another combination VEN with hypomethylating...
<p>Single cell analysis</p>
<p>Multivariate analysis of the TUH cohort</p>
<p>Figure S2</p>
<p>Figure S3</p>
<p>Figure S1</p>
<p>CD36 gene signature</p>
<p>Human antibodies for flow cytometry analyses (TUH cohort)</p>
<p>Supplemental Text</p>
<p>Single cell analysis</p>
<p>CD36 gene signature</p>
<p>Multivariate analysis of the TUH cohort</p>
<p>Human antibodies for flow cytometry analyses (TUH cohort)</p>
<p>Supplemental Text</p>
<p>Figure S1</p>