A5033024636- Cancer, Lipids, and Metabolism
- RNA modifications and cancer
- Ferroptosis and cancer prognosis
- Acute Myeloid Leukemia Research
- Protein Degradation and Inhibitors
- Histone Deacetylase Inhibitors Research
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Chronic Myeloid Leukemia Treatments
- Peptidase Inhibition and Analysis
- Cancer, Hypoxia, and Metabolism
- Hematopoietic Stem Cell Transplantation
- Lung Cancer Research Studies
- Epigenetics and DNA Methylation
- Chronic Lymphocytic Leukemia Research
- Sphingolipid Metabolism and Signaling
- Cancer Genomics and Diagnostics
- Immune cells in cancer
- Immune Cell Function and Interaction
- Retinoids in leukemia and cellular processes
- Multiple Myeloma Research and Treatments
- Platelet Disorders and Treatments
- Acute Lymphoblastic Leukemia research
- Signaling Pathways in Disease
- Autoimmune and Inflammatory Disorders Research
- Autophagy in Disease and Therapy
Université de Toulouse
2011-2025
Centre Hospitalier Universitaire de Toulouse
2013-2025
Université Toulouse III - Paul Sabatier
2012-2025
Institut universitaire du cancer de Toulouse Oncopole
2005-2024
Inserm
2011-2023
Centre de Recherche en Cancérologie de Toulouse
2011-2023
Centre National de la Recherche Scientifique
2005-2023
La Ligue Contre le Cancer
2019-2023
ideXlab (France)
2023
Hôpital Larrey
2018
Human leukemic stem cells, like other cancer are hypothesized to be rare, capable of incomplete differentiation, and restricted a phenotype associated with early hematopoietic progenitors or cells. However, recent work in types tumors has challenged the cell model. Using robust model xenotransplantation based on NOD/SCID/IL2Rγc-deficient mice, we confirmed that human functionally defined by us as SCID leukemia-initiating cells (SL-ICs), rare acute myelogenous leukemia (AML). In contrast...
Abstract Although transcription factor CCAAT-enhancer binding protein α (C/EBPα) is critical for normal and leukemic differentiation, its role in cell metabolic homeostasis largely unknown cancer. Here, multiomics analyses uncovered a coordinated activation of C/EBPα Fms-like tyrosine kinase 3 (FLT3) that increased lipid anabolism vivo patients with FLT3-mutant acute myeloid leukemia (AML). Mechanistically, regulated the fatty acid synthase (FASN)–stearoyl-CoA desaturase (SCD) axis to...
Abstract Donor lymphocyte infusion (DLI) prevents acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) relapses following hematopoietic stem cell transplantation. Given the life‐threatening toxicities such as graft versus host disease (GVHD), identification of variables associated with response without is warranted. We hypothesized that HLA evolutionary divergence (HED), defined by diversity between two given alleles same gene, may be a factor. A retrospective multicenter...
Most chromosomal translocations in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) involve oncogenes that are either up-regulated or form part of new chimeric genes. The t(2;11)(p21;q23) translocation has been cloned 19 cases MDS AML. In addition to this, we have shown this is associated with a strong up-regulation miR-125b (from 6- 90-fold). vitro experiments revealed was able interfere primary human CD34+ cell differentiation, also inhibited terminal (monocytic...
Abstract Autophagy has been associated with oncogenesis one of its emerging key functions being contribution to the metabolism tumors. Therefore, deciphering mechanisms how autophagy supports tumor cell is essential. Here, we demonstrate that inhibition induces an accumulation lipid droplets (LD) due a decrease in fatty acid β-oxidation, leads reduction oxidative phosphorylation (OxPHOS) acute myeloid leukemia (AML), but not normal cells. Thus, autophagic process participates catabolism...
In acute myeloid leukemia (AML), internal tandem duplication mutations in the FLT3 tyrosine kinase receptor (FLT3-ITD) account for up to 25% of cases and are associated with a poor outcome. order better target this AML subtype, comprehensive view how FLT3-ITD impacts cell biology is required. Here, we found that expression increased basal autophagy cells, both pharmacological genetic inhibition reduced primary samples lines. Conditional shRNAs against key proteins demonstrated required...
Abstract We aimed to study the prognostic impact of mutational landscape in primary and secondary myelofibrosis. The included 479 patients with myelofibrosis recruited from 24 French Intergroup Myeloproliferative Neoplasms (FIM) centers. molecular was studied by high-throughput sequencing 77 genes. A Bayesian network allowed identification genomic groups whose a multistate model considering transitions 3 conditions: myelofibrosis, acute leukemia, death. Results were validated using an...
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...
Abstract Focal adhesion kinase (FAK) is a nonreceptor tyrosine playing an important role in cell motility and survival. However, very little known about FAK normal leukemic myeloid cells. In this study, protein expression mRNA were detected 25 of 60 cases (42%) acute leukemia (AML). Whereas was expressed 46% CD34+ AML cells, it not purified Conversely, the homologue proline-rich 2 (PYK2) found to be both When expressed, displayed phosphorylation on Tyr-397, step for its activation. Moreover,...
Anthracyclines such as daunorubicin (DNR) generate radical oxygen species (ROS), which account, at least in part, for their cytotoxic effect. We observed that early ceramide generation (within 6–10 min) through neutral sphingomyelinase stimulation was inhibitable by the antioxidants <i>N-</i>acetylcysteine and pyrrolidine dithiocarbamate, led to a decrease apoptosis (>95% DNA fragmentation after 6 h). Furthermore, we DNR triggers c-Jun N-terminal kinase (JNK) transcription factor...
Hemophagocytic lymphohistiocytosis is a condition of immune dysregulation characterized by severe organ damage induced hyperinflammatory response and uncontrolled T-cell macrophage activation. Secondary hemophagocytic typically occurs in association with infections or malignancies. Patients acute myeloid leukemia may be prone to develop because an impaired high susceptibility infections. In series 343 patients treated intensive chemotherapy over 5-year period our center, we identified 32...
Acute myeloid leukemias (AML) with myelodysplasia-related changes (AML-MRC) are defined by the presence of multilineage dysplasia (MLD), and/or myelodysplastic syndrome (MDS)-related cytogenetics, previous MDS. The goal this study was to identify distinct biological and prognostic subgroups based on mutations ASXL1, RUNX1, DNMT3A, NPM1, FLT3 TP53 in 125 AML-MRC patients according MLD, cytogenetics outcome. ASXL1 (n=26, 21%) were associated a higher proportion marrow dysgranulopoiesis (mutant...
Chronic myeloid leukaemia (CML) is characterised by a progression from chronic towards an acute phase. We previously reported that signal transducer and activator of transcription 3 (STAT3), major oncogenic signalling protein, the target p210-BCR-ABL in murine embryonic stem (ES) cell model primary CD34+ CML cells. This activation was associated with inhibition differentiation ES The present study found BCR-ABL greatly phosphorylated STAT3 Ser727 residue and, to lesser extent, Tyr705...
Abstract Classifications of acute myeloid leukemia (AML) patients rely on morphologic, cytogenetic, and molecular features. Here we have established a novel flow cytometry-based immunophenotypic stratification showing that AML blasts are blocked at specific stages differentiation where features normal myelopoiesis preserved. Six differentiation-arrest categories based CD34, CD117, CD13, CD33, MPO, HLA-DR expression were identified in two independent cohorts 2087 1209 patients. Hematopoietic...
The Janus kinase 2 (JAK2)-driven myeloproliferative neoplasms (MPNs) are chronic malignancies associated with high-risk complications and suboptimal responses to JAK inhibitors such as ruxolitinib. A better understanding of cellular changes induced by ruxolitinib is required develop new combinatory therapies improve treatment efficacy. Here, we demonstrate that autophagy in JAK2V617F cell lines primary MPN patient cells through the activation protein phosphatase 2A (PP2A). Inhibition or PP2A...