0000000000385150

AUTHOR

Philippe Leboulch

showing 2 related works from this author

Optimization of retroviral-mediated gene transfer to human NOD/SCID mouse repopulating cord blood cells through a systematic analysis of protocol var…

1999

Abstract Retroviral transduction of human hematopoietic stem cells is still limited by lack of information about conditions that will maximize stem cell self-renewal divisions in vitro. To address this, we first compared the kinetics of entry into division of single human CD34 + CD38 − cord blood (CB) cells exposed in vitro to three different flt3-ligand (FL)-containing cytokine combinations. Of the three combinations tested, FL + hyperinterleukin 6 (HIL-6) yielded the least clones and these developed at a slow rate. With either FL + Steel factor (SF) + HIL-6 + thrombopoietin (TPO) or FL + SF + interleukin 3 (IL-3) + IL-6 + granulocyte-colony-stimulating factor (G-CSF), >90% of the cells th…

Cancer ResearchGenetic VectorsCD34Antigens CD34Stem cell factorMice SCIDCD38BiologyImmunophenotypingViral vectorMiceNAD+ NucleosidaseAntigens CDMice Inbred NODTransduction GeneticGeneticsAnimalsHumansADP-ribosyl CyclaseMolecular BiologyInterleukin 3Membrane GlycoproteinsGene Transfer TechniquesInfant NewbornMembrane ProteinsCell BiologyHematologyFetal BloodADP-ribosyl Cyclase 1Antigens DifferentiationVirologyMolecular biologyHaematopoiesisRetroviridaeCord bloodStem cellCell DivisionExperimental Hematology
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HSP70 sequestration by free α-globin promotes ineffective erythropoiesis in β-thalassaemia

2014

International audience; β-Thalassaemia major (β-TM) is an inherited haemoglobinopathy caused by a quantitative defect in the synthesis of β-globin chains of haemoglobin, leading to the accumulation of free α-globin chains that form toxic aggregates. Despite extensive knowledge of the molecular defects causing β-TM, little is known of the mechanisms responsible for the ineffective erythropoiesis observed in the condition, which is characterized by accelerated erythroid differentiation, maturation arrest and apoptosis at the polychromatophilic stage. We have previously demonstrated that normal human erythroid maturation requires a transient activation of caspase-3 at the later stages of matur…

Ineffective erythropoiesisCytoplasmErythroblastsCell SurvivalMutantApoptosis[ SDV.BBM.BM ] Life Sciences [q-bio]/Biochemistry Molecular Biology/Molecular biologyalpha-globin[SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC]Biologymedicine.disease_causeProtein Refolding03 medical and health sciences0302 clinical medicinealpha-GlobinsBone Marrowhemic and lymphatic diseasesmedicineHumans[ SDV.MHEP.HEM ] Life Sciences [q-bio]/Human health and pathology/HematologyErythropoiesisGATA1 Transcription FactorHSP70 Heat-Shock ProteinsMolecular Targeted TherapyCells CulturedHSP70030304 developmental biologyRegulation of gene expressionCell Nucleus0303 health sciencesMultidisciplinaryCaspase 3beta-Thalassemia[ SDV.BC.BC ] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC]GATA1[SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry Molecular Biology/Molecular biologyMolecular biologyHsp70Enzyme ActivationKineticsGene Expression RegulationCytoplasm030220 oncology & carcinogenesisChaperone (protein)biology.proteinErythropoiesisbeta-ThalassaemiaProtein Binding
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