The Experts below are selected from a list of 1905 Experts worldwide ranked by ideXlab platform
Jean-benoît Arlet - One of the best experts on this subject based on the ideXlab platform.
-
Unexpected macrophage-independent Dyserythropoiesis in Gaucher disease
Haematologica, 2016Co-Authors: Niloofar Reihani, Jean-benoît Arlet, Michael Dussiot, Olivier Hermine, Nadia Belmatoug, Caroline Le Van Kim, Thierry Billette De Villemeur, Christian Rose, Yves Colin Aronovicz, Mélanie FrancoAbstract:Gaucher disease is a rare inherited disease caused by a deficiency in glucocerebrosidase leading to lipid accumulation in cells of mononuclear-macrophage lineage known as Gaucher cells. Visceral enlargement, bone involvement, mild anemia and thrombocytopenia are the major manifestations of Gaucher disease. We have previously demonstrated that the red blood cells from patients exhibit abnormal properties, which indicates a new role in Gaucher disease pathophysiology. To investigate whether erythroid progenitors are affected, we examined the in vitro erythropoiesis from the peripheral CD34+ cells of patients and controls. CD34− cells were differentiated into macrophages and co-cultivated with erythroblasts. We showed an accelerated differentiation of erythroid progenitors without maturation arrest from patients compared to controls. This abnormal differentiation persisted in the patients when the same experiments were performed without macrophages, which strongly suggested that Dyserythropoiesis in Gaucher disease is secondary to an inherent defect in the erythroid progenitors. The accelerated differentiation was associated with reduced cell proliferation. As a result, less mature erythroid cells were generated in vitro in the Gaucher disease cultures compared to the control. We then compared the biological characteristics of untreated patients according to their anemic status. Compared to the non-anemic group, the anemic patients exhibit higher plasma levels of growth differentiation factor-15, a marker of ineffective erythropoiesis, but they had no indicators of hemolysis and similar reticulocyte counts. Taken together, these results demonstrated an unsuspected Dyserythropoiesis that was independent of the macrophages and could participate, at least in part, to the basis of anemia in Gaucher disease.
-
Protein-based therapeutic for anemia caused by Dyserythropoiesis.
Expert review of proteomics, 2016Co-Authors: Jean-benoît Arlet, Michael Dussiot, Ivan C. Moura, Olivier Hermine, Flavia Guillem, Mathilde Lamarque, Thiago Trovati Maciel, Geneviève CourtoisAbstract:ABSTRACTIntroduction: Major advances have been recently made in understanding the molecular determinants of Dyserythropoiesis, particularly due to recent works in β-thalassemia. The purpose of this review is devoted to underline the role of some proteins recently evidenced in the field, that may be new alternative therapeutic targets in the near future to alleviate different types of anemia.Areas covered: This review covers the contemporary aspects of some proteins involved in various types of Dyserythropoiesis, including the transcriptional factor GATA-1 and its protective chaperone HSP70, but also cytokines of the transforming growth factor beta (TFG-β) family, TGF-β1 and GDF-11, and hormones as erythroferrone. It will be not exhaustive, but based on major recent published works from the literature in the past three years.Expert commentary: Sotatercept and lustatercept, two activin receptor II ligand traps that block GDF-11, are candidate drugs providing therapeutic hope in different types of ineffectiv...
-
Novel players in β-thalassemia Dyserythropoiesis and new therapeutic strategies.
Current opinion in hematology, 2016Co-Authors: Jean-benoît Arlet, Michael Dussiot, Ivan C. Moura, Olivier Hermine, Geneviève CourtoisAbstract:Purpose of reviewThe review provides an overview of recent data regarding the molecular players in β-thalassemia Dyserythropoiesis and the corresponding therapeutic implications.Recent findingsβ-thalassemia Dyserythropoiesis is characterized by four steps: expansion of erythroid progenitors, acceler
-
An Unsuspected Dyserythropoiesis in Gaucher Disease
Blood, 2014Co-Authors: Niloofar Reihani, Jean-benoît Arlet, Olivier Hermine, Thierry Billette De Villemeur, Nadia Belmatoug, Yves Colin, Caroline Le Van Kim, Mélanie FrancoAbstract:Introduction : Gaucher disease (GD) is a lysosomal storage disorder, impairing glucosylceramide catabolism. GlcCer-laden macrophages transform into Gaucher cells and are responsible for the major GD symptoms (tissue infiltration, organomegaly, bone lesion). However, other signs of the disease such as anemia, spleen and bone infarcts might involve red blood cells (RBC). Despite the lysosomal characteristic of GD and the evidence of the central rdole of macrophages, our recent findings pointed out unexpected RBC abnormalities (Franco et al , Blood . 2013;121:546-555). These findings uncovered an overlooked aspect in GD showing that GD RBC exhibit abnormal rheological, morphological and membrane adhesion properties . Thus, RBC could be considered as culprit for ischemic events in GD. In this study, we analyzed the erythroid differentiation in GD to address the etiology of red cell abnormal behavior. We induced in vitro erythropoiesis from circulating GD patient progenitors. Methods : After purification of CD34 + cells from peripheral blood of Gaucher patients (n=20) or controls (CTL), erythroid progenitors were expanded in the absence of erythropoietin (EPO) and differentiated in a second step with erythropoietin. GD and CTL CD34 - cells were differentiated into macrophages by addition of M-CSF in the culture medium. To determine the effect of CTL and GD macrophages on normal erythropoiesis, in vitro generated macrophages were co-cultured with CTL erythroid progenitors in the presence of EPO. Proliferation of progenitors as well as erythroid differentiation were examined by flow cytometry and cytology. Results : Our preliminary results showed: (i) a dramatic decrease in proliferation of progenitors in the first step of expansion (** p p p Conclusion : We evidenced an unexpected Dyserythropoiesis characterized by accelerated erythroid differentiation in GD. The observed Dyserythropoiesis is independent of macrophage defects and is intrinsic to the GD erythroid lineage. These studies by helping to understand the role of erythroid cells in the pathophysiology of GD as well as the mechanism of anemia should prove useful for the development of additive therapies to alleviate debilitating clinical complications of this morbid disease such as osteonecrosis and splenomegaly. Disclosures Le Van Kim: SHIRE: Research Funding.
-
Ineffective Erythropoiesis in β-Thalassemia
The Scientific World Journal, 2013Co-Authors: Jean-antoine Ribeil, Jean-benoît Arlet, Michael Dussiot, Ivan C. Moura, Geneviève Courtois, Olivier HermineAbstract:In humans, β-thalassemia Dyserythropoiesis is characterized by expansion of early erythroid precursors and erythroid progenitors and then ineffective erythropoiesis. This ineffective erythropoiesis is defined as a suboptimal production of mature erythrocytes originating from a proliferating pool of immature erythroblasts. It is characterized by (1) accelerated erythroid differentiation, (2) maturation blockade at the polychromatophilic stage, and (3) death of erythroid precursors. Despite extensive knowledge of molecular defects causing β-thalassemia, less is known about the mechanisms responsible for ineffective erythropoiesis. In this paper, we will focus on the underlying mechanisms leading to premature death of thalassemic erythroid precursors in the bone marrow.
Geneviève Courtois - One of the best experts on this subject based on the ideXlab platform.
-
Protein-based therapeutic for anemia caused by Dyserythropoiesis.
Expert review of proteomics, 2016Co-Authors: Jean-benoît Arlet, Michael Dussiot, Ivan C. Moura, Olivier Hermine, Flavia Guillem, Mathilde Lamarque, Thiago Trovati Maciel, Geneviève CourtoisAbstract:ABSTRACTIntroduction: Major advances have been recently made in understanding the molecular determinants of Dyserythropoiesis, particularly due to recent works in β-thalassemia. The purpose of this review is devoted to underline the role of some proteins recently evidenced in the field, that may be new alternative therapeutic targets in the near future to alleviate different types of anemia.Areas covered: This review covers the contemporary aspects of some proteins involved in various types of Dyserythropoiesis, including the transcriptional factor GATA-1 and its protective chaperone HSP70, but also cytokines of the transforming growth factor beta (TFG-β) family, TGF-β1 and GDF-11, and hormones as erythroferrone. It will be not exhaustive, but based on major recent published works from the literature in the past three years.Expert commentary: Sotatercept and lustatercept, two activin receptor II ligand traps that block GDF-11, are candidate drugs providing therapeutic hope in different types of ineffectiv...
-
Novel players in β-thalassemia Dyserythropoiesis and new therapeutic strategies.
Current opinion in hematology, 2016Co-Authors: Jean-benoît Arlet, Michael Dussiot, Ivan C. Moura, Olivier Hermine, Geneviève CourtoisAbstract:Purpose of reviewThe review provides an overview of recent data regarding the molecular players in β-thalassemia Dyserythropoiesis and the corresponding therapeutic implications.Recent findingsβ-thalassemia Dyserythropoiesis is characterized by four steps: expansion of erythroid progenitors, acceler
-
Ineffective Erythropoiesis in β-Thalassemia
The Scientific World Journal, 2013Co-Authors: Jean-antoine Ribeil, Jean-benoît Arlet, Michael Dussiot, Ivan C. Moura, Geneviève Courtois, Olivier HermineAbstract:In humans, β-thalassemia Dyserythropoiesis is characterized by expansion of early erythroid precursors and erythroid progenitors and then ineffective erythropoiesis. This ineffective erythropoiesis is defined as a suboptimal production of mature erythrocytes originating from a proliferating pool of immature erythroblasts. It is characterized by (1) accelerated erythroid differentiation, (2) maturation blockade at the polychromatophilic stage, and (3) death of erythroid precursors. Despite extensive knowledge of molecular defects causing β-thalassemia, less is known about the mechanisms responsible for ineffective erythropoiesis. In this paper, we will focus on the underlying mechanisms leading to premature death of thalassemic erythroid precursors in the bone marrow.
Olivier Hermine - One of the best experts on this subject based on the ideXlab platform.
-
Unexpected macrophage-independent Dyserythropoiesis in Gaucher disease
Haematologica, 2016Co-Authors: Niloofar Reihani, Jean-benoît Arlet, Michael Dussiot, Olivier Hermine, Nadia Belmatoug, Caroline Le Van Kim, Thierry Billette De Villemeur, Christian Rose, Yves Colin Aronovicz, Mélanie FrancoAbstract:Gaucher disease is a rare inherited disease caused by a deficiency in glucocerebrosidase leading to lipid accumulation in cells of mononuclear-macrophage lineage known as Gaucher cells. Visceral enlargement, bone involvement, mild anemia and thrombocytopenia are the major manifestations of Gaucher disease. We have previously demonstrated that the red blood cells from patients exhibit abnormal properties, which indicates a new role in Gaucher disease pathophysiology. To investigate whether erythroid progenitors are affected, we examined the in vitro erythropoiesis from the peripheral CD34+ cells of patients and controls. CD34− cells were differentiated into macrophages and co-cultivated with erythroblasts. We showed an accelerated differentiation of erythroid progenitors without maturation arrest from patients compared to controls. This abnormal differentiation persisted in the patients when the same experiments were performed without macrophages, which strongly suggested that Dyserythropoiesis in Gaucher disease is secondary to an inherent defect in the erythroid progenitors. The accelerated differentiation was associated with reduced cell proliferation. As a result, less mature erythroid cells were generated in vitro in the Gaucher disease cultures compared to the control. We then compared the biological characteristics of untreated patients according to their anemic status. Compared to the non-anemic group, the anemic patients exhibit higher plasma levels of growth differentiation factor-15, a marker of ineffective erythropoiesis, but they had no indicators of hemolysis and similar reticulocyte counts. Taken together, these results demonstrated an unsuspected Dyserythropoiesis that was independent of the macrophages and could participate, at least in part, to the basis of anemia in Gaucher disease.
-
Protein-based therapeutic for anemia caused by Dyserythropoiesis.
Expert review of proteomics, 2016Co-Authors: Jean-benoît Arlet, Michael Dussiot, Ivan C. Moura, Olivier Hermine, Flavia Guillem, Mathilde Lamarque, Thiago Trovati Maciel, Geneviève CourtoisAbstract:ABSTRACTIntroduction: Major advances have been recently made in understanding the molecular determinants of Dyserythropoiesis, particularly due to recent works in β-thalassemia. The purpose of this review is devoted to underline the role of some proteins recently evidenced in the field, that may be new alternative therapeutic targets in the near future to alleviate different types of anemia.Areas covered: This review covers the contemporary aspects of some proteins involved in various types of Dyserythropoiesis, including the transcriptional factor GATA-1 and its protective chaperone HSP70, but also cytokines of the transforming growth factor beta (TFG-β) family, TGF-β1 and GDF-11, and hormones as erythroferrone. It will be not exhaustive, but based on major recent published works from the literature in the past three years.Expert commentary: Sotatercept and lustatercept, two activin receptor II ligand traps that block GDF-11, are candidate drugs providing therapeutic hope in different types of ineffectiv...
-
Novel players in β-thalassemia Dyserythropoiesis and new therapeutic strategies.
Current opinion in hematology, 2016Co-Authors: Jean-benoît Arlet, Michael Dussiot, Ivan C. Moura, Olivier Hermine, Geneviève CourtoisAbstract:Purpose of reviewThe review provides an overview of recent data regarding the molecular players in β-thalassemia Dyserythropoiesis and the corresponding therapeutic implications.Recent findingsβ-thalassemia Dyserythropoiesis is characterized by four steps: expansion of erythroid progenitors, acceler
-
An Unsuspected Dyserythropoiesis in Gaucher Disease
Blood, 2014Co-Authors: Niloofar Reihani, Jean-benoît Arlet, Olivier Hermine, Thierry Billette De Villemeur, Nadia Belmatoug, Yves Colin, Caroline Le Van Kim, Mélanie FrancoAbstract:Introduction : Gaucher disease (GD) is a lysosomal storage disorder, impairing glucosylceramide catabolism. GlcCer-laden macrophages transform into Gaucher cells and are responsible for the major GD symptoms (tissue infiltration, organomegaly, bone lesion). However, other signs of the disease such as anemia, spleen and bone infarcts might involve red blood cells (RBC). Despite the lysosomal characteristic of GD and the evidence of the central rdole of macrophages, our recent findings pointed out unexpected RBC abnormalities (Franco et al , Blood . 2013;121:546-555). These findings uncovered an overlooked aspect in GD showing that GD RBC exhibit abnormal rheological, morphological and membrane adhesion properties . Thus, RBC could be considered as culprit for ischemic events in GD. In this study, we analyzed the erythroid differentiation in GD to address the etiology of red cell abnormal behavior. We induced in vitro erythropoiesis from circulating GD patient progenitors. Methods : After purification of CD34 + cells from peripheral blood of Gaucher patients (n=20) or controls (CTL), erythroid progenitors were expanded in the absence of erythropoietin (EPO) and differentiated in a second step with erythropoietin. GD and CTL CD34 - cells were differentiated into macrophages by addition of M-CSF in the culture medium. To determine the effect of CTL and GD macrophages on normal erythropoiesis, in vitro generated macrophages were co-cultured with CTL erythroid progenitors in the presence of EPO. Proliferation of progenitors as well as erythroid differentiation were examined by flow cytometry and cytology. Results : Our preliminary results showed: (i) a dramatic decrease in proliferation of progenitors in the first step of expansion (** p p p Conclusion : We evidenced an unexpected Dyserythropoiesis characterized by accelerated erythroid differentiation in GD. The observed Dyserythropoiesis is independent of macrophage defects and is intrinsic to the GD erythroid lineage. These studies by helping to understand the role of erythroid cells in the pathophysiology of GD as well as the mechanism of anemia should prove useful for the development of additive therapies to alleviate debilitating clinical complications of this morbid disease such as osteonecrosis and splenomegaly. Disclosures Le Van Kim: SHIRE: Research Funding.
-
Ineffective Erythropoiesis in β-Thalassemia
The Scientific World Journal, 2013Co-Authors: Jean-antoine Ribeil, Jean-benoît Arlet, Michael Dussiot, Ivan C. Moura, Geneviève Courtois, Olivier HermineAbstract:In humans, β-thalassemia Dyserythropoiesis is characterized by expansion of early erythroid precursors and erythroid progenitors and then ineffective erythropoiesis. This ineffective erythropoiesis is defined as a suboptimal production of mature erythrocytes originating from a proliferating pool of immature erythroblasts. It is characterized by (1) accelerated erythroid differentiation, (2) maturation blockade at the polychromatophilic stage, and (3) death of erythroid precursors. Despite extensive knowledge of molecular defects causing β-thalassemia, less is known about the mechanisms responsible for ineffective erythropoiesis. In this paper, we will focus on the underlying mechanisms leading to premature death of thalassemic erythroid precursors in the bone marrow.
Michael Dussiot - One of the best experts on this subject based on the ideXlab platform.
-
Unexpected macrophage-independent Dyserythropoiesis in Gaucher disease
Haematologica, 2016Co-Authors: Niloofar Reihani, Jean-benoît Arlet, Michael Dussiot, Olivier Hermine, Nadia Belmatoug, Caroline Le Van Kim, Thierry Billette De Villemeur, Christian Rose, Yves Colin Aronovicz, Mélanie FrancoAbstract:Gaucher disease is a rare inherited disease caused by a deficiency in glucocerebrosidase leading to lipid accumulation in cells of mononuclear-macrophage lineage known as Gaucher cells. Visceral enlargement, bone involvement, mild anemia and thrombocytopenia are the major manifestations of Gaucher disease. We have previously demonstrated that the red blood cells from patients exhibit abnormal properties, which indicates a new role in Gaucher disease pathophysiology. To investigate whether erythroid progenitors are affected, we examined the in vitro erythropoiesis from the peripheral CD34+ cells of patients and controls. CD34− cells were differentiated into macrophages and co-cultivated with erythroblasts. We showed an accelerated differentiation of erythroid progenitors without maturation arrest from patients compared to controls. This abnormal differentiation persisted in the patients when the same experiments were performed without macrophages, which strongly suggested that Dyserythropoiesis in Gaucher disease is secondary to an inherent defect in the erythroid progenitors. The accelerated differentiation was associated with reduced cell proliferation. As a result, less mature erythroid cells were generated in vitro in the Gaucher disease cultures compared to the control. We then compared the biological characteristics of untreated patients according to their anemic status. Compared to the non-anemic group, the anemic patients exhibit higher plasma levels of growth differentiation factor-15, a marker of ineffective erythropoiesis, but they had no indicators of hemolysis and similar reticulocyte counts. Taken together, these results demonstrated an unsuspected Dyserythropoiesis that was independent of the macrophages and could participate, at least in part, to the basis of anemia in Gaucher disease.
-
Protein-based therapeutic for anemia caused by Dyserythropoiesis.
Expert review of proteomics, 2016Co-Authors: Jean-benoît Arlet, Michael Dussiot, Ivan C. Moura, Olivier Hermine, Flavia Guillem, Mathilde Lamarque, Thiago Trovati Maciel, Geneviève CourtoisAbstract:ABSTRACTIntroduction: Major advances have been recently made in understanding the molecular determinants of Dyserythropoiesis, particularly due to recent works in β-thalassemia. The purpose of this review is devoted to underline the role of some proteins recently evidenced in the field, that may be new alternative therapeutic targets in the near future to alleviate different types of anemia.Areas covered: This review covers the contemporary aspects of some proteins involved in various types of Dyserythropoiesis, including the transcriptional factor GATA-1 and its protective chaperone HSP70, but also cytokines of the transforming growth factor beta (TFG-β) family, TGF-β1 and GDF-11, and hormones as erythroferrone. It will be not exhaustive, but based on major recent published works from the literature in the past three years.Expert commentary: Sotatercept and lustatercept, two activin receptor II ligand traps that block GDF-11, are candidate drugs providing therapeutic hope in different types of ineffectiv...
-
Novel players in β-thalassemia Dyserythropoiesis and new therapeutic strategies.
Current opinion in hematology, 2016Co-Authors: Jean-benoît Arlet, Michael Dussiot, Ivan C. Moura, Olivier Hermine, Geneviève CourtoisAbstract:Purpose of reviewThe review provides an overview of recent data regarding the molecular players in β-thalassemia Dyserythropoiesis and the corresponding therapeutic implications.Recent findingsβ-thalassemia Dyserythropoiesis is characterized by four steps: expansion of erythroid progenitors, acceler
-
Ineffective Erythropoiesis in β-Thalassemia
The Scientific World Journal, 2013Co-Authors: Jean-antoine Ribeil, Jean-benoît Arlet, Michael Dussiot, Ivan C. Moura, Geneviève Courtois, Olivier HermineAbstract:In humans, β-thalassemia Dyserythropoiesis is characterized by expansion of early erythroid precursors and erythroid progenitors and then ineffective erythropoiesis. This ineffective erythropoiesis is defined as a suboptimal production of mature erythrocytes originating from a proliferating pool of immature erythroblasts. It is characterized by (1) accelerated erythroid differentiation, (2) maturation blockade at the polychromatophilic stage, and (3) death of erythroid precursors. Despite extensive knowledge of molecular defects causing β-thalassemia, less is known about the mechanisms responsible for ineffective erythropoiesis. In this paper, we will focus on the underlying mechanisms leading to premature death of thalassemic erythroid precursors in the bone marrow.
S. N. Wolff - One of the best experts on this subject based on the ideXlab platform.
-
Ringed sideroblasts: a frequent observation after bone marrow transplantation.
Modern Pathology, 1995Co-Authors: William R. Macon, Tham Kt, John P. Greer, S. N. WolffAbstract:Dyserythropoiesis after bone marrow transplantation is common, but the presence of ringed sideroblasts (RS) has not been evaluated fully. To examine for RS, a combined silver and Perls' Prussian blue stain, shown previously to be more sensitive for detecting RS than Perls' Prussian blue stain alone, was used on post-transplant marrow aspirate sections from 39 patients who received marrow transplants (allogeneic, 28; autologous, 11) for a variety of disorders. Marrow aspirate sections were available for comparison from 11 of these patients before any treatment as well as from five patients with normal marrows and normal peripheral blood cell counts. Aspirates were not performed on donor marrows. By the modified silver stain, RS were present in 34 (87%) patients whose marrows were sampled 0.5 to 39 (median, 1.5) months post-transplant including 10 of 11 patients with autologous transplants (no graft versus host disease prophylaxis). In contrast, seven of 36 (19%) of these marrows contained RS when stained with Perls' reaction alone. Only one of 11 pretransplant marrows and none of five normal marrows contained RS when stained by either method. These results demonstrate that RS are present in most post-transplant marrows even beyond the usual period of reconstitution (28 days), and this finding can be included among the features of Dyserythropoiesis seen after transplantation. RS apparently are not related to pretransplant pathology or post-transplant therapy. This study also confirms previous observations that modified silver stains are more sensitive for detecting RS than Perls' Prussian blue stain.