Olivier Kosmider
A5018074362- Acute Myeloid Leukemia Research
- RNA modifications and cancer
- Ferroptosis and cancer prognosis
- Cancer, Lipids, and Metabolism
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Otitis Media and Relapsing Polychondritis
- Chronic Lymphocytic Leukemia Research
- Chronic Myeloid Leukemia Treatments
- Vascular Anomalies and Treatments
- Immunodeficiency and Autoimmune Disorders
- Lymphoma Diagnosis and Treatment
- Hemoglobinopathies and Related Disorders
- Protein Degradation and Inhibitors
- Epigenetics and DNA Methylation
- Histone Deacetylase Inhibitors Research
- Multiple Myeloma Research and Treatments
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Cancer Genomics and Diagnostics
- Hematopoietic Stem Cell Transplantation
- Peptidase Inhibition and Analysis
- Erythrocyte Function and Pathophysiology
- Immune Cell Function and Interaction
- Hematological disorders and diagnostics
- Histiocytic Disorders and Treatments
- Retinoids in leukemia and cellular processes
Assistance Publique – Hôpitaux de Paris
2016-2025
Hôpital Cochin
2016-2025
Institut Cochin
2016-2025
Université Paris Cité
2016-2025
Centre National de la Recherche Scientifique
2016-2025
Inserm
2016-2025
Acute Leukemia French Association
2025
Délégation Paris 5
2015-2024
La Ligue Contre le Cancer
2013-2023
Sorbonne Paris Cité
2012-2023
The myelodysplastic syndromes and myeloproliferative disorders are associated with deregulated production of myeloid cells. mechanisms underlying these not well defined.We conducted a combination molecular, cytogenetic, comparative-genomic-hybridization, single-nucleotide-polymorphism analyses to identify candidate tumor-suppressor gene common patients syndromes, disorders, acute leukemia (AML). coding sequence this gene, TET2, was determined in 320 patients. We analyzed the consequences...
BACKGROUND: Risk stratification and therapeutic decision-making for myelodysplastic syndromes (MDS) are based on the International Prognostic Scoring System–Revised (IPSS-R), which considers hematologic parameters cytogenetic abnormalities. Somatic gene mutations not yet used in risk of patients with MDS. METHODS: To develop a clinical-molecular prognostic model (IPSS-Molecular [IPSS-M]), pretreatment diagnostic or peridiagnostic samples from 2957 MDS were profiled 152 genes. Clinical...
Purpose Several prognostic scoring systems have been proposed for chronic myelomonocytic leukemia (CMML), a disease in which some gene mutations—including ASXL1—have associated with poor prognosis univariable analyses. We developed and validated score overall survival (OS) based on mutational status standard clinical variables. Patients Methods genotyped ASXL1 up to 18 other genes including epigenetic (TET2, EZH2, IDH1, IDH2, DNMT3A), splicing (SF3B1, SRSF2, ZRSF2, U2AF1), transcription...
A new autoinflammatory syndrome related to somatic mutations of UBA1 was recently described and called VEXAS ('Vacuoles, E1 Enzyme, X-linked, Autoinflammatory, Somatic syndrome').To describe clinical characteristics, laboratory findings outcomes syndrome.One hundred sixteen patients with were referred a French multicentre registry between November 2020 May 2021. The frequency median parameters vital status, from diagnosis the end follow-up, recorded.The main features found be skin lesions...
Risk stratification is critical in the care of patients with myelodysplastic syndromes (MDS). Approximately 10% have a complex karyotype (CK), defined as more than two cytogenetic abnormalities, which highly adverse prognostic marker. However, CK-MDS can carry wide range chromosomal abnormalities and somatic mutations. To refine risk patients, we examined data from 359 shared by International Working Group for MDS. Mutations were underrepresented exception TP53 mutations, identified 55%...
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...
Azacitidine can be effective in myelodysplastic syndromes (MDS) associated with inflammatory/autoimmune diseases. Vacuoles, E1 Enzyme, X-linked, Autoinflammatory, Somatic syndrome (VEXAS) is a new monogenic autoinflammatory caused by somatic ubiquitin-like modifier-activating enzyme 1 (UBA1) mutation, often MDS, whose treatment difficult and not yet codified. Based on French nationwide registry of 116 patients VEXAS, we report the efficacy safety azacitidine 11 VEXAS MDS. Clinical response...
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 Acquired mutations in the UBA1 gene were recently identified patients with severe adult-onset auto-inflammatory syndrome called VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic). However, precise physiological and clinical impact of these remains poorly defined. Here we study a unique prospective cohort patients. We show that monocytes from are quantitatively qualitatively impaired display features exhaustion aberrant expression chemokine receptors. In peripheral...
Vacuoles, E1 enzyme, X-linked, autoinflammatory and somatic (VEXAS) syndrome is an adult-onset disease associated with ubiquitin-like modifier-activating enzyme 1 (UBA1) mutations. We aimed to evaluate the efficacy safety of targeted therapies.
Abstract Most cellular ubiquitin signaling is initiated by UBA1, which activates and transfers to tens of E2 enzymes. Clonally acquired UBA1 missense mutations cause an inflammatory-hematologic overlap disease called VEXAS (vacuoles, E1, X-linked, autoinflammatory, somatic) syndrome. Despite extensive clinical investigation into this lethal disease, little known about the underlying molecular mechanisms. Here, dissecting VEXAS-causing mutations, we discovered that p.Met41 alter cytoplasmic...
Acquired somatic deletions and loss-of-function mutations in one or several codons of the TET2 (Ten-Eleven Translocation-2) gene were recently identified hematopoietic cells from patients with myeloid malignancies, including myeloproliferative disorders myelodys-plastic syndromes. The present study was designed to determine prevalence alterations chronic myelomonocytic leukemias.Blood bone marrow collected 88 phase leukemia 14 acute transformation a previously disease. Polymerase chain...
Four hundred and nine patients with chronic myelomonocytic leukemia (CMML) were included in the international collaborative study (268 (66%) 141 (34%) from Mayo clinic French consortium respectively). Thirty percent displayed an abnormal karyotype, including; 72% sole, 16% two, 11% complex abnormalities. The most common abnormalities included; +8 (23%), -Y (20%), -7/7q-(14%), 20q- (8%), +21 der(3q) (8%). Patients karyotype more likely to be elderly (P = 0.03), anemic 0.0009), have...