A5089115198- Acute Myeloid Leukemia Research
- Multiple Myeloma Research and Treatments
- Erythrocyte Function and Pathophysiology
- Hematopoietic Stem Cell Transplantation
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Neonatal Health and Biochemistry
- Blood properties and coagulation
- Single-cell and spatial transcriptomics
- Chronic Lymphocytic Leukemia Research
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Epigenetics and DNA Methylation
- Acute Lymphoblastic Leukemia research
- CRISPR and Genetic Engineering
- Hemoglobinopathies and Related Disorders
- Chronic Myeloid Leukemia Treatments
- Immune Cell Function and Interaction
- Hematological disorders and diagnostics
- Sepsis Diagnosis and Treatment
- Cytomegalovirus and herpesvirus research
- Histone Deacetylase Inhibitors Research
- RNA modifications and cancer
- Retinoids in leukemia and cellular processes
- CAR-T cell therapy research
- RNA Research and Splicing
- Virus-based gene therapy research
Centre Hospitalier Universitaire Amiens-Picardie
2015-2025
Université de Picardie Jules Verne
2017-2025
Boston Children's Hospital
2021-2025
Harvard University
2021-2025
Broad Institute
2021-2025
Dana-Farber Cancer Institute
2021-2025
Howard Hughes Medical Institute
2024-2025
Boston Children's Museum
2024
Hématopoïèse et immunologie
2018-2022
Hôpital Nord
2013-2014
Systematic evaluation of the impact genetic variants is critical for study and treatment human physiology disease. While specific mutations can be introduced by genome engineering, we still lack scalable approaches that are applicable to important setting primary cells, such as blood immune cells. Here, describe development massively parallel base-editing screens in hematopoietic stem progenitor Such enable functional variant effects across any differentiation state. Moreover, they allow...
Abstract The human blood system is maintained through the differentiation and massive amplification of a limited number long-lived haematopoietic stem cells (HSCs) 1 . Perturbations to this process underlie diverse diseases, but clonal contributions haematopoiesis how changes with age remain incompletely understood. Although recent insights have emerged from barcoding studies in model systems 2–5 , simultaneous detection cell states phylogenies natural barcodes humans remains challenging....
Abstract CPX-351 is a liposomal formulation of cytarabine and daunorubicin approved for the treatment adults with newly diagnosed, therapy-related acute myeloid leukemia (t-AML) or AML myelodysplasia-related changes (MRC-AML). We retrospectively analyzed efficacy safety in real-world setting 103 patients from 12 French centers, including evaluation molecular abnormalities at baseline minimal residual disease (MRD) responding patients, compared historical data set Bordeaux-Toulouse DATAML...
Gene therapy using hematopoietic stem and progenitor cells is altering the therapeutic landscape for patients with hematologic, immunologic, metabolic disorders but has not yet been successfully developed individuals bone marrow failure syndrome Diamond-Blackfan anemia (DBA). More than 30 mutations cause DBA through impaired ribosome function lead to inefficient translation of erythroid master regulator GATA1, providing a potential avenue intervention applicable all DBA, irrespective...
Hereditary xerocytosis is a dominantly inherited red cell membrane disorder caused in most cases by gain-of-function mutations PIEZO1, encoding mechanosensitive ion channel that translates mechanic stimulus into calcium influx. We found PIEZO1 was expressed early erythroid progenitor cells, and investigated whether it could be involved erythropoiesis, besides having role the homeostasis of mature hydration. In UT7 chemical activation using YODA1 repressed glycophorin A expression 75%. This...
Older adults with acute myeloid leukemia (AML) have a poor prognosis because frailty and the characteristics of disease limit use intensive chemotherapy (ICT). Treatment 5-azacitidine (5-AZA) or low-dose cytarabine (Cytarabine) (LDAC) - without venetoclax is currently recommended in this setting. However, we lack real-life data on response rates treatment outcomes. We conducted retrospective, multicenter registry study 279 older AML (median [interquartile range (IQR)] age: 76 [70-81]) having...
Most phenotype-associated genetic variants map to noncoding regulatory regions of the human genome, but their mechanisms remain elusive in most cases. We developed a highly efficient strategy, Perturb-multiome, simultaneously profile chromatin accessibility and gene expression single cells with CRISPR-mediated perturbation master transcription factors (TFs). examined connection between TFs, accessible regions, across genome throughout hematopoietic differentiation. discovered that within...
Abstract The selenoprotein glutathione peroxidase 4 (GPX4), the only member of family able to directly reduce cell membrane–oxidized fatty acids and cholesterol, was recently identified as central regulator ferroptosis. GPX4 knockdown in mouse hematopoietic cells leads hemolytic anemia increased spleen erythroid progenitor death. role during human erythropoiesis is unknown. Using vitro differentiation, we show here that GPX4-irreversible inhibition by 1S,3R-RSL3 (RSL3) its short hairpin...
The diagnosis of myelodysplastic syndromes (MDS) might be challenging and relies on the convergence cytological, cytogenetic, molecular factors. Multiparametric flow cytometry (MFC) helps diagnose MDS, especially when other features do not contribute to decision-making process, but its usefulness remains underestimated, mostly due a lack standardization cytometers. We present here an innovative model integrating artificial intelligence (AI) with MFC improve classification MDS. develop...
Most phenotype-associated genetic variants map to non-coding regulatory regions of the human genome. Moreover, associated with blood cell phenotypes are enriched in active during hematopoiesis. To systematically explore nature these regions, we developed a highly efficient strategy, Perturb-multiome, that makes it possible simultaneously profile both chromatin accessibility and gene expression single cells CRISPR-mediated perturbation range master transcription factors (TFs). This approach...
Monoclonal gammopathy of unknown significance (MGUS), smouldering multiple myeloma (SMM), and (MM) are very common neoplasms. However, it is often difficult to distinguish between these entities. In the present study, we aimed classify most powerful markers that could improve diagnosis by multiparametric flow cytometry (MFC). The study included 348 patients based on two independent cohorts. We first assessed how representative data were in discovery cohort (123 MM, 97 MGUS) then analysed...
CPX-351 has been approved for patients with therapy-related acute myeloid leukemia (t-AML) or AML myelodysplasia-related changes (MRC-AML). No extensive data are available on measurable residual disease (MRD) and long-term clinical outcome using in real life. We retrospectively collected from 168 36 centers France Italy who had received 1 2 cycles of induction CPX-351. All were aged >18 years newly diagnosed, untreated t-AML MRC-AML. With a median follow-up 3 years, the overall survival (OS)...
The impact of consolidation on response rates and PFS has recently been demonstrated after induction autotransplantation upfront in Multiple Myeloma (MM). We further showed that patients ≥VGPR following the intensification procedure benefited most from consolidation. Question remains as to benefit for PR at completion - feature partial resistance regimen. collected data 54 newly diagnosed MM treated with VTd-auto-VTd regimen reached only procedure. Overall, 37 (68%) improved depth (≥VGPR)...
Over the past 2 decades, it has become evident that a significant proportion of acute myeloid leukemia (AML) occurs on background predisposing germline aberrations. The diagnosis these disorders is clinical interest as may imply specific management AML patients, especially for selection intrafamilial hematopoietic stem cell (HSC) donors, well genetic counseling and/or surveillance in other family members. However, determination an underlying predisposition remains challenging1-3 and not...