A5057574703- Acute Myeloid Leukemia Research
- Protein Degradation and Inhibitors
- Epigenetics and DNA Methylation
- Ubiquitin and proteasome pathways
- Genomics and Chromatin Dynamics
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Cancer-related gene regulation
- Chronic Myeloid Leukemia Treatments
- Chronic Lymphocytic Leukemia Research
- Acute Lymphoblastic Leukemia research
- Glycosylation and Glycoproteins Research
- Bacteriophages and microbial interactions
- Viral Infectious Diseases and Gene Expression in Insects
- Renal and related cancers
- Advanced biosensing and bioanalysis techniques
- Histone Deacetylase Inhibitors Research
- Hematopoietic Stem Cell Transplantation
- Cancer-related Molecular Pathways
- Cancer Research and Treatments
- Lymphoma Diagnosis and Treatment
- Chromatin Remodeling and Cancer
- Cell death mechanisms and regulation
- Pancreatic function and diabetes
- Cutaneous lymphoproliferative disorders research
- PI3K/AKT/mTOR signaling in cancer
La Ligue Contre le Cancer
2017-2024
Inserm
2011-2024
Université Paris-Saclay
2011-2024
Institut Gustave Roussy
2011-2024
University of Cambridge
2022-2024
Wellcome/MRC Cambridge Stem Cell Institute
2022-2023
Medical Research Council
2023
Université Paris Cité
2011-2020
Université Paris-Sud
2011-2019
Délégation Paris 7
2019
Acute megakaryoblastic leukemia (AMKL) is a heterogeneous disease generally associated with poor prognosis. Gene expression profiles indicate the existence of distinct molecular subgroups, and several genetic alterations have been characterized in past years, including t(1;22)(p13;q13) trisomy 21 GATA1 mutations. However, majority patients do not present known mutations, limited access to primary patient leukemic cells impedes efficient development novel therapeutic strategies. In this...
Abstract Cellular differentiation requires extensive alterations in chromatin structure and function, which is elicited by the coordinated action of transcription factors. By contrast with factors, roles factors have not been systematically characterized. Here, we combine bulk ex vivo single-cell CRISPR screens to characterize role factor families hematopoiesis. We uncover marked lineage specificities for 142 revealing functional diversity among related (i.e. barrier-to-autointegration...
Fusion oncogenes are prevalent in several pediatric cancers, yet little is known about the specific associations between age and phenotype. We observed that fusion oncogenes, such as ETO2-GLIS2, associated with acute megakaryoblastic or other myeloid leukemia subtypes an age-dependent manner. Analysis of a novel inducible transgenic mouse model showed ETO2-GLIS2 expression fetal hematopoietic stem cells induced rapid whereas adult bone marrow resulted shift toward transformation strikingly...
Super Enhancers (SEs) are clusters of regulatory elements associated with cell identity and disease. However, whether these induced by oncogenes can regulate gene modules cooperating for cancer transformation or maintenance remains elusive. To address this question, we conducted a genome-wide CRISPRi-based screening SEs in ETO2-GLIS2 + acute megakaryoblastic leukemia. This approach revealed essential leukemic growth survival that expression. In particular, identified de novo SE specific...
Abstract Transcriptional cofactors of the ETO family are recurrent fusion partners in acute leukemia. We characterized ETO2 regulome by integrating transcriptomic and chromatin binding analyses human erythroleukemia xenografts controlled depletion models. demonstrate that beyond its well‐established repressive activity, directly activates transcription MYB, among other genes. The ETO2‐activated signature is associated with a poorer prognosis but also myeloid lymphoid leukemia subtypes....
The ETO2-GLIS2 fusion oncoprotein is associated with poor prognosis pediatric acute megakaryoblastic leukemia. Recently, we observed that controls enhancers activity at genes regulating haematopoietic progenitor self-renewal and differentiation toward the megakaryocytic lineage. We also showed targeting complex stability inhibits these properties may represent a novel therapeutic strategy.
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Abstract B-cell acute lymphoblastic leukemia (B-ALL) is an aggressive hematological malignancy of B lineage progenitors. It remains a leading cause death in childhood, while outcomes adults are dismal. There therefore need to better understand drivers high-risk B-ALL and develop novel therapeutic approaches targeting these challenging patient cohorts. Loss-of-function mutations affecting CREBBP recurrent second-hit across multiple genetic subtypes associated with adverse features, including...