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See detailPositron emission tomography in non-Hodgkin's lymphoma (NHL): relationship between tracer uptake and pathological findings, including preliminary experience in the staging of low-grade NHL.
Jerusalem, Guy ULg; Beguin, Yves ULg

in Clinical Lymphoma (2002), 3(1), 56-61

Advances in imaging techniques have allowed more precise staging and better evaluation of the effect of new treatment modalities. The limitations of conventional morphologic imaging techniques are well ... [more ▼]

Advances in imaging techniques have allowed more precise staging and better evaluation of the effect of new treatment modalities. The limitations of conventional morphologic imaging techniques are well known. Positron emission tomography (PET) using fluorine-18-labeled fluorodeoxyglucose is now routinely used for initial staging and re-evaluation during or after treatment of Hodgkin's disease and aggressive non-Hodgkin's lymphoma (NHL), but not in low-grade NHL. In the first part of this review, the relationship between glucose metabolism as measured by PET, pathological findings including histological grade and proliferative activity, and prognosis are analyzed. In the second part, the potential role of PET in the staging and follow-up of low-grade NHL is discussed. Published data indicate that PET may contribute to the management of low-grade follicular NHL. [less ▲]

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See detailPre-emptive immunotherapy with CD8-depleted donor lymphocytes after CD34-selected allogeneic peripheral blood stem cell transplantation.
Baron, Frédéric ULg; Siquet, Jean; Schaaf-Lafontaine, Nicole ULg et al

in Haematologica (2002), 87(1), 78-88

BACKGROUND AND OBJECTIVES: To maximize graft-versus-leukemia (GVL) effects while minimizing the risk of graft-versus-host disease (GVHD), we undertook a study of allogeneic CD34-selected peripheral blood ... [more ▼]

BACKGROUND AND OBJECTIVES: To maximize graft-versus-leukemia (GVL) effects while minimizing the risk of graft-versus-host disease (GVHD), we undertook a study of allogeneic CD34-selected peripheral blood stem cell (PBSC) transplantation followed by CD8-depleted donor lymphocyte infusion (DLI). DESIGN AND METHODS: Twenty-four patients with advanced hematologic malignancies were included. PBSC were collected in matched (N=16) or one-mismatch (N=8) related donors and CD34-selected. On day 60, donors donated lymphocytes that were CD8-depleted and separated into 3 aliquots containing 2 x 10(6), 1 x 10(7) and 5 x 10(7) CD3+ cells/kg (patients 1-13) or into 2 aliquots containing 1 x 10(7) and 5 x 10(7) CD3+ cells/kg (patients 14-24). The 1st aliquot was infused on day 60 and the other 1 (2) cryopreserved and infused on days 100 (and 140). RESULTS: An average of 100%, 100% and 84% of the scheduled dose could be administered in DLI 1, 2 and 3, respectively. Although the study group was at very high risk of GVHD, the actuarial incidence of grade II-IV acute GVHD was 28% (13% for HLA-identical siblings) with only 1 patient developing grade III-IV GVHD (after DLI). The actuarial 2-year probability of extensive chronic GVHD was similarly low (13% for all patients and 0% for HLA-identical siblings). Individual cases as well as a 30% relapse rate (0% for standard-risk patients versus 55% for high-risk patients) indicated preservation of the GVL effect. INTERPRETATION AND CONCLUSIONS: We conclude that allogeneic transplantation of CD34-selected PBSC followed by pre-emptive CD8-depleted DLI is feasible with rapid engraftment and minimizes the risk of severe GVHD. Large prospective trials are required to prove that it preserves the GVL effect fully. [less ▲]

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See detailOptimization of recombinant human erythropoietin therapy after allogeneic hematopoietic stem cell transplantation.
Baron, Frédéric ULg; Sautois, Brieuc ULg; Baudoux, Etienne ULg et al

in Experimental hematology (2002), 30(6), 546-54

OBJECTIVE: Allogeneic hematopoietic stem cell transplantation (HSCT) is associated with prolonged anemia caused by defective erythropoietin (Epo) production. We enrolled 34 recipients of an allogeneic ... [more ▼]

OBJECTIVE: Allogeneic hematopoietic stem cell transplantation (HSCT) is associated with prolonged anemia caused by defective erythropoietin (Epo) production. We enrolled 34 recipients of an allogeneic HSCT in three consecutive trials to determine the optimal utilization of recombinant human erythropoietin (rhEpo) therapy in this setting. MATERIALS AND METHODS: In the first trial (n = 7), rhEpo 1400 U/kg/week was given from day 1 until a hemoglobin (Hb) level of 10 g/dL was achieved, for a maximum of 60 days. In the second trial, rhEpo 500 U/kg/week was given to achieve Hb levels of 13 to 14 g/dL in 13 anemic patients with fatigue 56 to 1440 days after transplant. In the third trial, rhEpo was scheduled to start on day 35 in 14 patients at a dose of 500 U/kg/week with the aim of achieving Hb levels of 13 to 14 g/dL. RESULTS: In trial 1, erythroid recovery to 1% reticulocytes and red blood cell transfusion independence were faster, but the number of transfusions was not reduced compared to 10 controls. Responses were brisk in trial 2, with transfusion independence achieved after a median of 1 week in 12 of 13 patients, and 2-g Hb increments or Hb values of 11, 12, and 13 g/dL after 6, 7, 10, and 10 weeks, respectively. Transfusions were significantly reduced in the first month of rhEpo therapy. In trial 3, transfusion independence was obtained after a median of 1 week in 13 of 14 patients, and 2-g Hb increments or Hb values of 11, 12, and 13 g/dL after 3, 4, 6, and 8 weeks, respectively. Transfusions rates were considerably reduced compared to the previous month in the same patients or compared to controls undergoing peripheral blood or marrow transplant without rhEpo. CONCLUSIONS: Anemia after allogeneic HSCT is exquisitely sensitive to rhEpo. The benefit is minimal when it is given early post-transplant, as used in all trials to date. However, the rate of major response is greater than 90% when rhEpo is started after day 35. These data provide the basis on which to conduct a prospective, randomized, placebo-controlled trial of rhEpo therapy after allogeneic HSCT. [less ▲]

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See detailErythropoiesis after nonmyeloablative stem-cell transplantation is not impaired by inadequate erythropoietin production as observed after conventional allogeneic transplantation.
Baron, Frédéric ULg; Fillet, Georges ULg; Beguin, Yves ULg

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 ▲]

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See detailPreemptive cellular immunotherapy after T-cell-depleted allogeneic hematopoietic stem cell transplantation.
Baron, Frédéric ULg; Beguin, Yves ULg

in Biology of Blood & Marrow Transplantation (2002), 8(7), 351-9

GVHD is a life-threatening complication of allogeneic hematopoietic stem cell transplantation (HSCT). GVHD is due to donor lymphocytes that are cotransplanted with donor stem cells. These donor ... [more ▼]

GVHD is a life-threatening complication of allogeneic hematopoietic stem cell transplantation (HSCT). GVHD is due to donor lymphocytes that are cotransplanted with donor stem cells. These donor lymphocytes are primed by histocompatibility differences between donors and recipients and activated by a cytokine storm caused by the conditioning regimen. The most efficient method for prevention of GVHD consists of T-cell depletion (TCD) of the graft. However, TCD usually leads to an increased risk of leukemia relapse because of the loss of the graft-versus-leukemia (GVL) effect. Several groups have studied the feasibility of preemptive donor lymphocyte infusion (DLI) to lessen the impact of TCD on leukemia relapse. Preemptive DLI is given several weeks to months after the transplantation, ie, after the cytokine storm and after the patient has recovered from conditioning-regimen-related toxicities. After briefly discussing various techniques of TCD of the graft and the efficacy of DLI, this article reviews the first clinical studies evaluating a strategy of TCD of the graft followed by preemptive DLI. [less ▲]

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See detailNonmyeloablative allogeneic hematopoietic stem cell transplantation.
Baron, Frédéric ULg; Beguin, Yves ULg

in Journal of Hematotherapy & Stem Cell Research (2002), 11(2), 243-63

Allogeneic hematopoietic stem cell transplantation (HSCT) is the most effective treatment for selected hematological malignancies. Its curative potential is largely mediated by an immune-mediated ... [more ▼]

Allogeneic hematopoietic stem cell transplantation (HSCT) is the most effective treatment for selected hematological malignancies. Its curative potential is largely mediated by an immune-mediated destruction of malignant cells by donor lymphocytes termed graft-versus-leukemia (GVL) effect. However, because of its toxicity, conventional allogeneic HSCT is restricted to younger and fitter patients. These observations led several groups to set up new (less toxic) transplant protocols (nonmyeloablative stem cell transplantation or NMSCT) based on a two-step approach: first, the use of immunosuppressive (but nonmyeloablative) preparative regimens providing sufficient immunosuppression to achieve engraftment of allogeneic hematopoietic stem cells and, in a second step, destruction of malignant cells by the GVL effect. Preliminary results showed that NMSCT were feasible with a relatively low transplant-related mortality (TRM), even in patients older than 65 years. In addition, strong antitumor responses were observed in several hematological malignancies as well as in some patients with renal cell carcinoma. After discussing the mechanisms and efficacy of the GVL effect as well as the rationale for NMSCT strategies, this article reviews the first results of ongoing clinical trials. Innovative modalities that may permit amplification of the GVL effect while minimizing the risk of GVHD are discussed. Because the benefits of NMSCT over alternative forms of treatment remain to be demonstrated, this strategy should be restricted to patients included in clinical trials. [less ▲]

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See detailNonmyeloablative stem cell transplantation with CD8-depleted or CD34-selected peripheral blood stem cells.
Baron, Frédéric ULg; Baudoux, Etienne ULg; Frere, Pascale ULg et al

in Journal of Hematotherapy & Stem Cell Research (2002), 11(2), 301-14

To decrease the incidence of graft-versus-host disease (GVHD) observed after nonmyeloablative stem cell transplantation (NMSCT), we studied the feasibility of CD8-depleted or CD34-selected NMSCT followed ... [more ▼]

To decrease the incidence of graft-versus-host disease (GVHD) observed after nonmyeloablative stem cell transplantation (NMSCT), we studied the feasibility of CD8-depleted or CD34-selected NMSCT followed by CD8-depleted preemptive donor lymphocyte infusion (DLI) given in incremental doses on days 40 and 80. Fourteen patients with high-risk malignancies and an HLA-identical sibling (n = 8) or alternative donor (n = 6) but ineligible for a conventional transplant were included. Nonmyeloablative conditioning regimen consisted in 2 Gy total body irradiation (TBI) alone, 2 Gy TBI and fludarabine (previously untreated patients) or cyclophosphamide and fludarabine (patients who had previously received > or =12 Gy TBI). Patients 1-4 (controls) received unmanipulated peripheral blood stem cells (PBSC) and DLI and patients 5-14 CD8-depleted or CD34-selected PBSC followed by CD8-depleted DLI. Post-transplant immunosuppression was carried out with cyclosporine A (CsA) and mycophenolate mofetil (MMF). Initial engraftment was seen in all patients, but 1 patient (7%) later rejected her graft. The actuarial 180-day incidence of grades II-IV acute GVHD was 75% for patients 1-4 versus 0% for patients 5-14 (p = 0.0019). Five of 14 patients were in complete remission (CR) 180 days after the transplant and 6/14 had partial responses. The 1-year survival rate was 69%, and nonrelapse and relapse mortality rates were 16 and 18%, respectively. We conclude that CD8-depleted or CD34-selected NMSCT followed by CD8-depleted DLI is feasible and considerably decreases the incidence of acute GVHD while preserving engraftment and apparently also the graft-versus-leukemia (GVL) effect. Further studies are needed to confirm this encouraging preliminary report. [less ▲]

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See detailRetrospective comparison of CD34-selected allogeneic peripheral blood stem cell transplantation followed by CD8-depleted donor lymphocyte infusions with unmanipulated bone marrow transplantation.
Baron, Frédéric ULg; Baudoux, Etienne ULg; Fillet, Georges ULg et al

in Hematology (2002), 7(3), 137-43

We have previously reported the feasibility of allogeneic CD34-selected PBSC transplantation followed by pre-emptive CD8-depleted DLI (study group). In this report, we retrospectively compare the clinical ... [more ▼]

We have previously reported the feasibility of allogeneic CD34-selected PBSC transplantation followed by pre-emptive CD8-depleted DLI (study group). In this report, we retrospectively compare the clinical outcome of the 24 patients included in this study with an historical group of 35 patients receiving unmanipulated marrow (BMT group). Patients in the study group had significantly faster neutrophil and platelet recovery and were discharged earlier than BMT patients. The actuarial 150-day (after DLI) probability of developing grade II-IV acute GVHD was 28% for the study group versus 62% for the BMT group (p=0.002). The actuarial 2-year probability of developing chronic GVHD was similar (37 versus 36% (NS)) but chronic GVHD was significantly delayed in the study group (p=0.003). The actuarial 2-year probability of relapse was 30% in the study group versus 33% in the BMT group (NS). The actuarial 2-year probability of survival was 45% in the study group versus 43% in the BMT group (NS). We conclude that allogeneic transplantation of CD34-selected PBSC followed by pre-emptive CD8-depleted DLI is feasible with rapid engraftment and minimizes the risk of severe GVHD. Large prospective trials are required to confirm these results. [less ▲]

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See detailInternational forum. Use of umbilical cord blood progenitor cells as an alternative for bone marrow transplantation.
Engelfriet, C. P.; Reesink, H. W.; Wagner, J. E. et al

in Vox Sanguinis (2002), 83(2), 172-87

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See detailStunting may determine the severity of malaria-associated anemia in African children.
Verhoef, Hans; West, Clive E; Veenemans, Jacobien et al

in Pediatrics (2002), 110(4), 48

OBJECTIVE: Evidence from previous studies that malnourished children are protected against malaria is controversial. In individuals repeatedly exposed to malaria, immunity may develop first against severe ... [more ▼]

OBJECTIVE: Evidence from previous studies that malnourished children are protected against malaria is controversial. In individuals repeatedly exposed to malaria, immunity may develop first against severe disease, then against pyrogens, and last, against parasites. If this is true, this would suggest that reduced immune function that may exist in stunted children exacerbates the severity of malarial signs and symptoms, rather than the occurrence of parasitemia. On the other hand, several studies have suggested that malnourished children are protected to some degree against malaria. Our aim was to evaluate whether observational data support the hypothesis that nutritional inadequacies that cause stunting modify the associations between malaria and hematologic indicators such as hemoglobin concentration and serum concentrations of C-reactive protein and soluble transferrin receptor (sTfR). We showed earlier that increased serum concentrations of these receptors in asymptomatic malaria may be explained, at least in part, by increased erythropoiesis to compensate for malaria-induced hemolysis. METHODOLOGY: Community-based cluster survey among Kenyan children aged 2 to 36 months asymptomatic for malaria or anemia (n = 318). RESULTS: When adjusted for age and wasting, the malaria-associated decrease in mean hemoglobin concentration was 8.5 g/L and 15.8 g/L in nonstunted and stunted children, respectively. The malaria-associated increase in geometric mean serum concentrations of sTfR was 1.1-fold and 1.8-fold in nonstunted and stunted children, respectively. The malaria-associated increase in geometric mean serum concentrations of C-reactive protein was 1.4-fold and 2.3-fold in nonstunted and stunted children, respectively. Thus, children with malaria and those who were stunted suffered from more severe anemia and had higher serum concentrations of C-reactive protein and sTfR than would be expected from the combined effect of the 2 working independently. CONCLUSIONS: Our results are consistent with the notion that the nutritional inadequacies causing stunting also impair host immunity, thus increasing the degree to which malaria is associated with decreased concentrations of hemoglobin, with increased inflammation, and with increased iron demand in developing erythroblasts. Increased intake of micronutrients may not only reduce stunting and nutritional anemia, but also reduce malaria-associated anemia. [less ▲]

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See detailPrediction of response and other improvements on the limitations of recombinant human erythropoietin therapy in anemic cancer patients.
Beguin, Yves ULg

in Haematologica (2002), 87(11), 1209-21

BACKGROUND AND OBJECTIVES: The majority of cancer patients suffer from chronic anemia. While recombinant human erythropoietin (rHuEPO) offers many of the advantages of blood transfusions, response rates ... [more ▼]

BACKGROUND AND OBJECTIVES: The majority of cancer patients suffer from chronic anemia. While recombinant human erythropoietin (rHuEPO) offers many of the advantages of blood transfusions, response rates to this treatment are variable and in some trials a large proportion of patients (30 50%) did not respond. This failure may be due to factors related to the underlying disease, the chemotherapy given or functional iron deficiency. An accurate means of predicting response to rHuEPO would be beneficial to both healthcare providers and patients. EVIDENCE AND INFORMATION SOURCES: Data were identified by searches of the published literature, including PubMed, references from relevant reviews, and abstracts presented at recent international oncology and hematology meetings. Only papers in English published between 1990 and 2002 were included. References were selected according to direct relevance to the topic discussed and availability. STATE OF THE ART: The best algorithms for predicting response appear to be those combining an assessment of the adequacy of endogenous erythropoietin production together with some early indicators of erythropoietic marrow response. Further characterization of the dose-response relationship of erythropoietic agents may allow better understanding of ways in which response may be enhanced. Adequate iron availability could also contribute to better response rates. PERSPECTIVES: Further characterization of the predictors of response for current and upcoming erythropoietic agents may enhance the management of anemia associated with cancer, and provide more convenient, effective, and flexible therapy. [less ▲]

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See detailComment etablir le bilan de fin de traitement des patients atteints de lymphomes non-hodgkiniens (LNH) de malignite intermediaire ou elevee?
Warland, V.; Jerusalem, Guy ULg; Hustinx, Roland ULg et al

in Revue Médicale de Liège (2002), 57(12), 779-84

Incomplete regression of a lymphomatous mass after chemotherapy and/or radiotherapy constitutes a major problem in the treatment of lymphoma. In patients with persisting tumor, it could be reasonable to ... [more ▼]

Incomplete regression of a lymphomatous mass after chemotherapy and/or radiotherapy constitutes a major problem in the treatment of lymphoma. In patients with persisting tumor, it could be reasonable to use salvage therapy and possibly hematopoietic stem cell transplantation at the time of minimal disease rather than at the time of clinically overt relapse. The authors reviewed the most appropriate imaging techniques for the assessment of response to treatment. The limitations of CT and MRI for predicting the nature of residual masses are well known. 67Ga scintigraphy has become a standard procedure for the posttreatment evaluation of patients with lymphoma, but it appears that 18F-FDG PET may be a more effective method. Personal experience in the field of PET scan is reported. Although PET should be considered the noninvasive imaging modality of choice, a histological confirmation of residual disease is always necessary before starting salvage therapy. 18F-fluorodeoxyglucose is not a tumor specific radiotracer. [less ▲]

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See detailOutpatient and home parenteral antibiotic therapy (OHPAT) in low-risk febrile neutropenia: consensus statement of a Belgian panel.
Beguin, Yves ULg; Benoit, Yves; Crokaert, F. et al

in Acta Clinica Belgica (2002), 57(6), 309-16

Febrile neutropenia requires adequate antibiotic treatment. A subgroup of patients are only at low risk for complications and could be treated at home/as outpatients (OHPAT) after a short initial ... [more ▼]

Febrile neutropenia requires adequate antibiotic treatment. A subgroup of patients are only at low risk for complications and could be treated at home/as outpatients (OHPAT) after a short initial admission for work up. This position paper by a Belgian panel of experts presents criteria defining low-risk in febrile neutropenia, gives an overview of the existing experience and examines the present obstacles to a more widespread use of OHPAT in this country. [less ▲]

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See detailPredictive factors for response of anemia to recombinant human erythropoietin
Beguin, Yves ULg

in Nowrousian, M. R. (Ed.) Recombinant human erythropoietin (rhEPO) in clinical oncology (2002)

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See detailIncreased binding and defective migration across fibronectin of cycling hematopoietic progenitor cells.
Giet, Olivier ULg; Van Bockstaele, Dirk R; Di Stefano, Ivano et al

in Blood (2002), 99(6), 2023-31

Engraftment of hematopoietic progenitor cells has been shown to decrease during cell cycle transit. We studied cell cycle-associated changes in adhesion and migration of mitotically activated cord blood ... [more ▼]

Engraftment of hematopoietic progenitor cells has been shown to decrease during cell cycle transit. We studied cell cycle-associated changes in adhesion and migration of mitotically activated cord blood CD34+ cells. Migration toward medium conditioned by the stromal-derived factor-1-producing cell line MS-5 was studied in bovine serum albumin- and fibronectin (Fn)-coated transwells. Migration was reduced in cycling CD34+ cells and long-term culture-initiating cells (LTC-ICs) compared with their noncycling counterparts across Fn but not across bovine serum albumin. Conversely, Fn binding was higher in cycling CD34+ cells and LTC-ICs compared with noncycling progenitor cells, while adhesion of both subsets to bovine serum albumin was undetectable. The contribution of alpha4 and alpha5 integrins in mediating adhesion and migration of activated CD34+ cells onto Fn was analyzed by neutralization experiments. While alpha4-mediated Fn binding decreased during G(2)/M, alpha5 integrin-mediated adhesion increased during transit from G(0)/G(1) to S and G(2)/M phases. As for migration, the contribution of alpha4 integrin was similar in all phases, whereas alpha5-directed migration was lower in G(2)/M compared with G(0)/G(1) and S phases. Defective migration of cycling CD34+ cells was not due to differences in alpha5 integrin expression. In conclusion, chemotaxis across Fn is less efficient in cycling progenitor cells in correlation with an increased Fn binding capacity. In addition, alpha4 and alpha5 integrin functions are independently modulated during cell cycle transit. [less ▲]

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See detailAdhesion of synchronized human hematopoietic progenitor cells to fibronectin and vascular cell adhesion molecule-1 fluctuates reversibly during cell cycle transit in ex vivo culture.
Huygen, Sandra; Giet, Olivier ULg; Artisien, Vincent et al

in Blood (2002), 100(8), 2744-52

Ex vivo expansion of hematopoietic stem/progenitor cells may result in defective engraftment. Human cord blood CD34(+) progenitor cells were synchronized and assayed for adhesion and migration onto ... [more ▼]

Ex vivo expansion of hematopoietic stem/progenitor cells may result in defective engraftment. Human cord blood CD34(+) progenitor cells were synchronized and assayed for adhesion and migration onto fibronectin (Fn) and vascular cell adhesion molecule-1 (VCAM-1) at different stages of a first cell cycle executed ex vivo. During S phase transit, adhesion to Fn was transiently increased while binding to VCAM-1 was reversibly decreased, after which adhesion to both ligands returned to baseline levels with cell cycle completion. Transmigration across Fn and VCAM-1 decreased irreversibly during S phase progression. The function of alpha4 and alpha5 integrins was assessed with specific neutralizing antibodies. In uncultured CD34(+) cells and long-term culture-initiating cells (LTC-ICs), both adhesion and migration on Fn were inhibited by anti-alpha4 but not by anti-alpha5 antibodies. In mitotically activated CD34(+) cells and LTC-ICs, adhesion and migration on Fn were mainly dependent on alpha5 integrin and to a lesser extent on alpha4 integrin. Changes in integrin function were not dependent on parallel modulation of integrin expression. In conclusion, Fn and VCAM-1 binding of progenitor cells fluctuates reversibly during cell cycle transit ex vivo. In addition, our data show that mitogenic activation induces a shift from a dominant alpha4 to a preferential alpha5 integrin-dependent interaction with Fn. [less ▲]

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See detailMonitoring of erythropoiesis by the serum transferrin receptor and erythropoietin.
Fillet, Georges ULg; Beguin, Yves ULg

in Acta Clinica Belgica (2001), 56(3), 146-54

Virtually all cells have transferrin receptors (a transmembrane glycoprotein) on their surface but in a normal adult, 80% of them are in the erythroid marrow. Some of them are lost into the circulation ... [more ▼]

Virtually all cells have transferrin receptors (a transmembrane glycoprotein) on their surface but in a normal adult, 80% of them are in the erythroid marrow. Some of them are lost into the circulation where they can be measured by immuno-assays. A direct and highly significant correlation exists between serum transferrin receptor level and erythron transferrin uptake in humans. The measurement of serum transferrin receptor has wide clinical applications for the quantitation of erythropoiesis. It can be used to study erythropoiesis in situations in which ferrokinetics is not acceptable such as pregnancy. It is particularly useful for serial studies, e.i., for monitoring the recovery of erythropoiesis after stem cell transplantation or after treatment with erythropoietin. Combined with the determination of serum erythropoietin, both evaluated in relation to the degree of anemia, they provide a physiological approach to the diagnosis of anemia. Thus, the simultaneous determination of hematocrit, reticulocytes, serum transferrin receptor and serum erythropoietin has high discriminatory value in distinguishing between a defect in erythroid proliferation, maturation or red cell survival. It is also particularly useful for detecting the presence of multiple mechanisms of anemia in the same patient. [less ▲]

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