L’érythropoïèse tardive : une mort avortée ?
; ; et al
in Hématologie (2007), 13(6), 400-408
La survie et la prolifération des progéniteurs et précurseurs érythroïdes se trouvent sous le contrôle de l’érythropoïétine (Epo), qui est le principal régulateur de l’érythropoïèse. La différenciation ... [more ▼]
La survie et la prolifération des progéniteurs et précurseurs érythroïdes se trouvent sous le contrôle de l’érythropoïétine (Epo), qui est le principal régulateur de l’érythropoïèse. La différenciation érythroïde s’effectue sous la dépendance du facteur de transcription GATA-1 qui active l’expression des gènes de différenciation et de survie. La production des globules rouges est finement régulée par l’inhibition ou au contraire par l’induction de l’apoptose des progéniteurs et des précurseurs érythroïdes. La baisse du taux d’Epo circulante ou l’induction de la voie Fas aboutissent à l’activation de la caspase-3 qui entraîne la protéolyse de GATA-1, l’arrêt de maturation et l’apoptose des érythroblastes immatures. Nous avons montré qu’une activation transitoire de la caspase-3 par la voie mitochondriale est indispensable à la maturation érythroïde. Dans ce contexte, la protéine chaperonne hsp70 joue un rôle majeur en protégeant GATA-1 du clivage par la caspase-3. La différenciation terminale est caractérisée par une réduction progressive du volume cellulaire et du noyau associée à une condensation de la chromatine. Ces changements morphologiques présentent certaines similitudes avec ceux observés dans les cellules en cours d’apoptose. L’énucléation s’effectue ensuite au sein d’îlots érythroblastiques constitués d’un macrophage central étroitement associé par des molécules d’adhérence à des érythroblastes en cours de maturation. La membrane de l’érythroblaste perd progressivement son affinité pour le macrophage alors que le noyau reste fixé, ce qui permet l’énucléation et la phagocytose du noyau par le macrophage. Les réticulocytes ainsi formés vont compléter leur maturation en perdant leurs organelles et en remodelant leur membrane. Nos études suggèrent que le devenir des précurseurs érythroïdes (apoptose versus différenciation) est déterminé par le choix des cibles clivées par les caspases. Si la fonction du clivage de certaines protéines telles que la lamine B ou acinus est bien connue, l’identité et la fonction des autres cibles clivées par les caspases au cours de la maturation terminale restent à déterminer. [less ▲]Detailed reference viewed: 57 (0 ULg)
Erythropoiesis after nonmyeloablative stem-cell transplantation is not impaired by inadequate erythropoietin production as observed after conventional allogeneic transplantation.
Baron, Frédéric ; Fillet, Georges ; Beguin, Yves
in Transplantation (2002), 74(12), 1692-6
BACKGROUND: It is now well established that after conventional allogeneic hematopoietic stem-cell transplantation (HSCT), erythropoietic recovery is impaired because erythropoietin (Epo) production ... [more ▼]
BACKGROUND: It is now well established that after conventional allogeneic hematopoietic stem-cell transplantation (HSCT), erythropoietic recovery is impaired because erythropoietin (Epo) production remains inadequate for prolonged periods of time. However, erythropoietic reconstitution after nonmyeloablative SCT (NMSCT) has never been characterized. METHODS: Twelve patients received a nonmyeloablative conditioning regimen consisting of 2 Gy total body irradiation (TBI) alone (n=6), 2 Gy TBI and fludarabine (n=3), or cyclophosphamide and fludarabine (n=3), followed by transplantation of allogeneic peripheral blood stem cells. Graft-versus-host-disease (GvHD) prophylaxis was carried out with mycophenolate mofetil (from day -1 to day 28) plus cyclosporine (from day -1 to day 120 or longer in case of chronic GvHD). Erythropoiesis was quantitated by soluble transferrin receptor (sTfR) levels, and the adequacy of Epo production was evaluated by the observed-to-predicted Epo ratio (O/P Epo). RESULTS: Mean sTfR levels decreased following the conditioning regimen but remained well within the normal range throughout the posttransplant period. The O/P Epo ratio presented an initial surge quite similar to that observed after conventional conditioning. Thereafter, the O/P Epo ratio normalized rapidly, and Epo levels remained adequate during the whole observation period. CONCLUSION: Contrarily to what is observed after myeloablative transplant, Epo levels remained adequate after NMSCT, resulting in normal erythropoiesis. These results suggest that the administration of erythropoietin therapy (rHuEpo) could be less effective after NMSCT than after conventional allogeneic transplant. [less ▲]Detailed reference viewed: 16 (2 ULg)
Erythropoiesis and erythropoietin in multiple myeloma.
in Leukemia & Lymphoma (1995), 18(5-6), 413-21
In this review, the pathophysiology and treatment of the anemia of multiple myeloma will be examined. While the anemia of cancer has multiple causes, an important component is labeled the "anemia of ... [more ▼]
In this review, the pathophysiology and treatment of the anemia of multiple myeloma will be examined. While the anemia of cancer has multiple causes, an important component is labeled the "anemia of chronic disease" which is characterized by the combination of a shortened erythrocyte survival with failure of the bone marrow to increase red cell production in compensation. Depressed erythropoiesis is itself related to a combination of factors, including impaired availability of storage iron, inadequate erythropoietin response to anemia, and overproduction of cytokines which are capable of inhibiting erythropoiesis. These cytokines are involved in the retention of iron in the reticuloendothelial system, gastrointestinal tract and hepatocytes, may interfere with erythropoietin production by the kidney, and may exert direct inhibitory effects on erythroid precursors. While overproduction of several such cytokines, including IL-6, IL-1 and TNF-alpha, has been definitely demonstrated in multiple myeloma patients, it is still unclear whether they are directly involved in the pathogenesis of the anemia which develops. Although several mechanisms, such as hemodilution, bleeding, and decreased red cell survival operate, the anemia is mostly caused by defective erythropoietic activity. This in turn is partly explained by inadequate erythropoietin (Epo) production even in some patients without renal impairment. Based on measurements of serum erythropoietin and transferrin receptor, the distinction between marrow unresponsiveness to normal Epo stimulation and deficient Epo production is important for the treatment of the anemia of multiple myeloma with recombinant human Epo. Higher doses would probably be necessary if adequate Epo production is present, whereas only replacement therapy with lower doses may be sufficient when Epo production has been shown to be inappropriate. [less ▲]Detailed reference viewed: 31 (3 ULg)
Erythropoiesis and renal transplant pregnancy.
; ; et al
in Clinical Transplantation (2000), 14(2), 127-35
OBJECTIVE: To examine erythropoiesis in renal transplant pregnancies. METHODS: Retrospective cohort study of 30 renal transplant cases and 30 age, smoking and parity-matched healthy controls with normal ... [more ▼]
OBJECTIVE: To examine erythropoiesis in renal transplant pregnancies. METHODS: Retrospective cohort study of 30 renal transplant cases and 30 age, smoking and parity-matched healthy controls with normal index pregnancy. Retrospective chart review and assay of frozen antenatal serum (for serum erythropoietin concentration [serum EPO]), transferrin receptor protein [TfR], ferritin, folate and B12) were performed. The linear regression equation for normal pregnancy controls was used to calculate predicted [serum EPO] and the observed/predicted (O/P) log [serum EPO] was plotted. The relationship between [serum EPO] and haemoglobin (Hb) among transplant cases was considered to be different from that among controls if the slope of the O/P log [serum EPO] versus Hb regression was significantly different from zero. RESULTS: The transplant (14 cadaveric) to conception interval was (median [range]) 33.5 [4, 189] months. Immunosuppressants were azathioprine (n = 25), cyclosporine (n = 22) and/or prednisone (n = 25). Cases were more often primiparous (20 vs. 7 [controls]; p = 0.01), had pre-existent hypertension (20 vs. 0 [controls]; p < 0.001), developed new/increased hypertension or pre-eclampsia (28 vs. 0 [controls]; p < 0.001) and an antenatal rise in creatinine (14 vs. 2 [controls]; p < 0.001). In early pregnancy, cases had similar EPO (15.2 [2.6, 84.6] vs. 15.7 [6.4, 41.0] [controls] U/L) but lower Hb (101 [65, 129] vs. 116 [106, 150] g/L; p < 0.001). Twenty-two (73%) cases had Hb < 100 g/L (vs. 4 [controls]; p < 0.0001); Hb was comparable at 6 wk postpartum. With advancing gestational age (GA), Hb remained stable and serum EPO increased in both groups. The slope of the O/P log [serum EPO] versus Hb for transplant cases was significantly different from zero within both the 17-28 wk (slope +/- SEM: 0.010 +/- 0.002; p < 0.0001) and the 29-42 wk GA categories (0.006 +/- 0.003; p = 0.02). Cases showed smaller rises in serum TfR (change 481 [- 1471, 2780]) vs. 1119 [- 698, 4195] [controls] ng/mL; p = 0.005). CONCLUSIONS: Anaemia frequently complicates renal transplant pregnancies, in which serum EPO is inappropriately low and the rate of erythropoiesis blunted. [less ▲]Detailed reference viewed: 22 (0 ULg)
Erythropoiesis in acromegaly : effect of GH or IGF-1 ? Data from the LAS (Liege Acromegaly Survey)
PETROSSIANS, Patrick ; ; et al
in Journal für Klinische Endokrinologie und Stoffwechsel (2012, September), 5(3), 45Detailed reference viewed: 21 (3 ULg)
Erythropoiesis in multiple myeloma: defective red cell production due to inappropriate erythropoietin production.
Beguin, Yves ; ; et al
in British Journal of Haematology (1992), 82(4), 648-53
We investigated the pathophysiology of erythropoiesis in 62 patients with multiple myeloma and examined whether it would establish a rational basis for the treatment of their anaemia with recombinant ... [more ▼]
We investigated the pathophysiology of erythropoiesis in 62 patients with multiple myeloma and examined whether it would establish a rational basis for the treatment of their anaemia with recombinant human erythropoietin. Erythropoietin (Epo) production was evaluated by serum levels and erythropoiesis was quantitated by serum transferrin receptor (TfR) levels, both assessed relative to the degree of anaemia. Instead of the expected stimulation of erythropoiesis in response to anaemia, haematocrit correlated positively with marrow erythropoietic activity, indicating that the mechanism of anaemia was primarily defective red cell production. Erythropoiesis decreased and anaemia worsened significantly with advancing clinical stage. 25% of the patients had inadequate Epo production and this proportion increased to 50% in stage 3. Inappropriate Epo production was seen in 60% of patients with renal impairment but was also observed in a number of patients with normal renal function. Erythropoiesis correlated strongly with the adequacy of Epo production, particularly in advanced disease. We conclude that most myeloma patients have defective red cell production even in the absence of massive marrow infiltration and that inappropriate Epo production contributes to their anaemia. [less ▲]Detailed reference viewed: 26 (6 ULg)
Erythropoietic activity and iron metabolism in autologous blood donors during recombinant human erythropoietin therapy.
; ; Beguin, Yves et al
in European Journal of Clinical Investigation (1994), 24(6), 426-32
The use of recombinant human erythropoietin (rhEPO) to intensify the erythropoietic response in autologous donors may reduce homologous blood requirement. We studied the effect of subcutaneous rhEPO (500 ... [more ▼]
The use of recombinant human erythropoietin (rhEPO) to intensify the erythropoietic response in autologous donors may reduce homologous blood requirement. We studied the effect of subcutaneous rhEPO (500 U kg-1 body weight twice weekly during a 3 week period) on variables of erythropoiesis and iron metabolism in 62 autologous blood donors, of whom 32 received rhEPO (epo group) and 30 did not (control group). Patients donated only 2 units of blood and received oral iron in order to restrict phlebotomy-induced decrease of iron stores. Pre-phlebotomy haemoglobin concentration (14.0 +/- 0.8 g dl-1) was completely regenerated in the epo group at surgery (13.7 +/- 1.3 g dl-1); haemoglobin concentration in the control group fell from 13.5 +/- 1.4 g dl-1 to 11.6 +/- 1.4 g dl-1 after the phlebotomies and did not improve during the pre-operative phase. Total erythropoietic activity expressed as serum transferrin receptor concentration (sTfR) showed a 4-fold increase from 3.8 +/- 0.9 micrograms ml-1 to 14.9 +/- 4.8 micrograms ml-1 in the epo group. Effective erythropoietic activity measured by absolute reticulocyte count, however, declined after the fourth rhEPO injection in the epo group. Serum ferritin was lower in the epo group, but no differences in serum iron, transferrin concentration and transferrin saturation were observed between the groups. A marked increase in free erythrocyte protoporphyrin (FEP) was observed in the epo group, whereas FEP levels in the controls remained within normal ranges. Despite oral iron supplementation and the limited number of phlebotomies, the effect of rhEPO therapy in autologous donors is restricted by iron depletion. [less ▲]Detailed reference viewed: 42 (4 ULg)
Erythropoietin and platelet production.
in Haematologica (1999), 84(6), 541-7
BACKGROUND AND OBJECTIVE: Erythropoietin (Epo) is the primary growth factor for the red cell lineage but treatment with recombinant human Epo (rHuEpo) has been shown to increase platelet counts. In ... [more ▼]
BACKGROUND AND OBJECTIVE: Erythropoietin (Epo) is the primary growth factor for the red cell lineage but treatment with recombinant human Epo (rHuEpo) has been shown to increase platelet counts. In several animal species treatment with rHuEpo stimulated platelet production, but platelet counts tended to normalize after 1-2 weeks and large, chronic doses even caused thrombocytopenia. This paper aims to review the evidence about the effects of Epo on megakaryopoiesis. INFORMATION SOURCES: I examined the literature published in journals covered by Medline(R)a concerning the effects of Epo, hypoxia and iron deficiency on megakaryopoiesis and platelets. The reference list of each article was reviewed to try to identify further contributions. STATE OF THE ART: In vivo data have shown that moderate Epo stimulation, i.e. that produced by standard doses of rHuEpo, short-term hypoxia or moderate iron deficiency, causes a moderate elevation of platelet counts, whereas intense Epo stimulation, as produced by high doses of rHuEpo, prolonged hypoxia or severe iron deficiency, causes some degree of thrombocytopenia. In the latter case, there appears to be a diphasic response to Epo, the initial positive response (a stimulation of platelet production) being followed by thrombocytopenia. Contrarily to the thrombocytopenia due to increased platelet destruction induced by other growth factors, Epo-induced thrombocytopenia is the result of an inhibition of platelet production. CONCLUSION AND PERSPECTIVE: Stem-cell competition between erythroid and platelet precursors appears to be the cause of these phenomena in situations of prolonged, intense stimulation by Epo. In vitro data support the existence of a common erythrocytic and megakaryocytic precursor. It remains to be determined whether these effects of rHuEpo are a result of the dose itself or of the magnitude of the erythropoietic effect of that dose. It is not known whether a lower dose given in a patient with decreased marrow function would bring about the same biological effects as those induced by high doses of rHuEpo in the presence of a normal marrow function. Caution should be exercised before using high doses of hematopoietic growth factors. [less ▲]Detailed reference viewed: 25 (0 ULg)
Erythropoietin and the anemia of cancer.
in Acta Clinica Belgica (1996), 51(1), 36-52
The pathogenesis of the anemia of cancer involves the combination of a shortened erythrocyte survival in circulation with the failure of bone marrow to increase red cell production in compensation ... [more ▼]
The pathogenesis of the anemia of cancer involves the combination of a shortened erythrocyte survival in circulation with the failure of bone marrow to increase red cell production in compensation. Inappropriate red cell production is itself related to a conjunction of factors, including impaired availability of reticuloendothelial storage iron, inadequate erythropoietin (Epo) response to anemia, and overproduction of cytokines which are capable of inhibiting erythropoiesis. Many of these cytokines may interfere with erythropoietin production by the kidney. Consequently inadequate serum erythropoietin levels are often encountered in cancer patients, though more frequently in those with solid tumors or multiple myeloma than in those with other hematologic malignancies. There is little evidence supporting a negative impact of chemotherapy, including cisplatin, on erythropoietin production. Rather, chemotherapy usually causes a transient elevation of serum Epo. Red cell transfusions are often administered to cancer patients, possibly resulting, among other deleterious effects, in enhancement of tumor growth. Recombinant human erythropoietin (rHuEpo) has thus been proposed as an alternative. RHuEpo has been shown to be safe and effective in correcting the anemia of cancer and reducing the need for transfusions. The response rate is as good in hematologic malignancies as in solid tumors, but it is extremely poor in those with myelodysplastic syndromes. The effect of rHuEpo does not differ among patients receiving or not receiving chemotherapy, including cisplatin. The probability of response is also similar in patients with adequate or inappropriate erythropoietin production before therapy, although the doses used are usually 2 to 3 times higher than in renal failure patients. [less ▲]Detailed reference viewed: 21 (2 ULg)
Erythropoietin improves quality of life--a response.
; ; Van Steen, Kristel et al
in Lancet Oncology (2002), 3(9), 527Detailed reference viewed: 7 (2 ULg)
Erythropoietin therapy after allogeneic hematopoietic cell transplantation : a prospective randomised trial.
JASPERS, Aurélie ; Baron, Frédéric ; WILLEMS, Evelyne et al
in Belgian Journal of Hematology (2013, January)
Based on the impairment of erythropoietin production after allogeneic hematopoietic cell transplantation (HCT), we previously reported in a phase-2 trial that recombinant human erythropoietin (rhEPO ... [more ▼]
Based on the impairment of erythropoietin production after allogeneic hematopoietic cell transplantation (HCT), we previously reported in a phase-2 trial that recombinant human erythropoietin (rhEPO) therapy was very efficient when started one month after transplantation. We also demonstrated that anemia after nonmyeloabalative (NM) HCT was less sensitive to rhEPO therapy than after conventional allogeneic HCT. This prompted us to confirm these findings in a prospective randomised trial. One hundred and thirty-one patients were randomised (1:1) between no treatment (arm 1) or erythropoietin (Neorecormon) at the dose of 500 U/kg/week (arm 2). Once the target Hb (13g/dL) has been attained, the dose of rhEPO was reduced by half, while it was withheld when Hb was = 14g/dL. Cohort A included 42 patients on day 28 after myeloablative HCT, cohort B 39 patients on day 28 after NMHCT, and cohort C 50 patients on day 0 of NMHCT. Primary endpoints included proportion of complete correctors (i.e. patients reaching Hb = 13g/dL) and median time to achieve Hb correction in each arm. The proportion of complete correctors before day 126 posttransplant was 0% in group 1A vs 52.4% in group 2A, 0% in group 1B vs 69.5% in group 2B and 19.1% in group 1C vs 70.2% in group 2C. Median time to achieve Hb = 13g/dL was not reached in group 1B vs 49 days in group 2B; 363 and 59 days in groups 1A and 1B respectively and 363 and 87 days in groups 3A and 3B respectively (figure 1). Hb evolution in each group is shown in figure 2. Seventyone patients (47/62 in control groups and 24/57 in treated groups, p=0.0003) required red blood cell transfusions. The difference was most pronounced in cohort B. There was no difference in rates of thrombo-embolic events or other complications between the two arms. In conclusion, this is the first trial to demonstrate that EPO therapy hastens erythroid recovery and decreases transfusion requirements when started one month after allogeneic HCT. [less ▲]Detailed reference viewed: 29 (11 ULg)
Erythropoietin therapy after allogeneic hematopoietic cell transplantation : a prospective randomized trial
JASPERS, Aurélie ; Baron, Frédéric ; WILLEMS, Evelyne et al
in Blood (in press)
We conducted a prospective randomized trial to assess hemoglobin (Hb) response to recombinant human erythropoietin (rhEPO) therapy after hematopoietic cell transplantation (HCT). Patients (n=131) were ... [more ▼]
We conducted a prospective randomized trial to assess hemoglobin (Hb) response to recombinant human erythropoietin (rhEPO) therapy after hematopoietic cell transplantation (HCT). Patients (n=131) were randomized (1:1) between no treatment (control arm) or erythropoietin (Neorecormon®) at 500 U/kg/week (EPO arm). Patients were also stratified in 3 cohorts: patients undergoing myeloablative HCT with rhEPO to start on day 28, patients given nonmyeloablative HCT (NMHCT) with rhEPO to start on day 28, and patients also given NMHCT but with rhEPO to start on day 0. The proportion of complete correctors (i.e. achieving Hb ≥ 13 g/dL) before day 126 post-transplant (primary endpoint) was 8.1% in the control arm (median not reached) and 63.1% in the EPO arm (median time 90 days) (p<0.001). Hb levels were higher and transfusions requirements decreased (p<0.001) in the EPO arm, but not during the first month in the nonmyeloablative cohort starting rhEPO on day 0. There was no difference in rates of thrombo-embolic events or other complications between the 2 arms. This is the first randomized trial to demonstrate that rhEPO therapy hastens erythroid recovery and decreases transfusion requirements when started one month after allogeneic HCT. There was no benefit to start rhEPO earlier after NMHCT. [less ▲]Detailed reference viewed: 11 (2 ULg)
Erythropoïétine : utilisation diagnostique et thérapeutique
Beguin, Yves ; Fillet, Georges
in Revue de l’Association Belge des Technologues de Laboratoire = Tijdschrift van de Belgische Vereniging van Laboratoriumtechnologen (1991), 18(3), 161-168
L'érythropoïétine est une hormone produite par le rein en réponse à une hypoxie rénale et qui stimule l'activité érythropoïétique de la moelle osseuse. Le dosage de l'érythropoïétine sérique, toujours ... [more ▼]
L'érythropoïétine est une hormone produite par le rein en réponse à une hypoxie rénale et qui stimule l'activité érythropoïétique de la moelle osseuse. Le dosage de l'érythropoïétine sérique, toujours interprété en fonction de l'hématocrite circulant, est utile dans le diagnostic différentiel des polyglobulies et dans certains cas particuliers d'anémie. L'utilisation thérapeutique de l'érythropoïétine recombinante a permis de corriger l'anémie de l'insuffisance rénale chronique et est actuellement étudiée dans d'autres indications telles que les anémies inflammatoires. [less ▲]Detailed reference viewed: 41 (4 ULg)
Erythropoietine: utilisation diagnostique et therapeutique.
Beguin, Yves ; Fillet, Georges
in Revue Médicale de Liège (1990), 45(6), 261-7Detailed reference viewed: 24 (4 ULg)
Erzählen von Differenzen. Nach 25 Jahren Auseinandersetzung mit Uwe Johnsons Werk veröffentlicht Norbert Mecklenburg seinen zweiten Sammelband, Nachbarschaften mit Unterschieden
in Literaturkritik.de (2005), 9Detailed reference viewed: 23 (7 ULg)
Erzählte Kindsbräute bei Heinrich von Kleist, E.T.A. Hoffmann und Theodor Storm
in Detering, Heinrich; Fasold, Regina; Stein, Malte (Eds.) Zwischen Mignon und Lulu. Das Phantasma der Kindsbraut in Biedermeier und Realismus (2010)Detailed reference viewed: 47 (0 ULg)