Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0596978 (Leukemia)
 15,069 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sera of 25 healthy controls and 75 patients suffering from myelodysplastic syndromes (MDS) were investigated for serum concentration of interleukin-1 alpha (IL-1 alpha), IL-3, IL-6, granulocyte-colony-stimulating factor (G-CSF), granulocyte-macrophage-CSF (GM-CSF), erythropoietin (Epo), and tumor necrosis factor-alpha (TNF-alpha). According to French-American-British (FAB) classification, 21 refractory anemia (RA), seven refractory anemia with ring sideroblasts (RARS), 15 chronic myelomonocytic leukemia (CMML), 12 refractory anemia with excess of blasts (RAEB), and 20 RAEB in transformation (RAEBt) were examined. TNF-alpha levels were inversely correlated with lower levels of hemoglobin concentration (r = -0.31, p = 0.005), irrespective of the requirements for transfusion in anemic MDS patients. Significant differences in TNF-alpha levels between CMML (26.2 +/- 5.9 pg/ml) and the FAB subgroups (16.1 +/- 1.6 pg/ml) were detected. There was an overall inverse relationship between the level of erythropoietin and the degree of anemia, but a wide range of Epo response between patients with similar hemoglobin concentrations. Serum levels of IL-1 alpha and GM-CSF were undetected in most of the patients. In 57% of the samples there were detectable levels of G-CSF, without a correlation of the serum levels with blood cell counts, nor with any of the FAB subcategories. Overall, 29% and 25% of the patient sera exhibited elevated IL-3 and IL-6 levels, respectively. There was no correlation of the serum levels with any of the blood counts, other cytokines, nor FAB subcategories. In conclusion, simple negative feedback mechanism between a specific cytokine and the production of blood cells seems not to be the case in MDS, except for red cell production and erythropoietin concentration. Our data may suggest the involvement of TNF-alpha in the pathogenesis of anemia in MDS.
Leukemia 1992 Dec
PMID:Measurement of serum cytokine levels in patients with myelodysplastic syndromes. 128 Jul 51

As an introduction to a Satellite Symposium on the utilization of recombinant human erythropoietin (rHu-EPO) in hematology (Leukemia & Lymphoma 1992; 7 (Suppl.2): 94-100) a contribution to its mechanism of action was presented, and is published here. In three patients with advanced Hodgkin's disease treated with combination chemotherapy (MOPP) incorporating vincristine, and receiving at the same time a fixed daily dose of 8000 U of rHu-EPO subcutaneously for 10 to 15 days because of myelosuppressive anemia, myeloaspirates were performed one week before and 24 hours after the administration of vincristine. A dramatic accumulation of arrested metaphases in all stages of erythroblasts was found, while there was no augmentation of granulocytic metaphases. This is a further confirmation, following a previous contribution (Marmont AM: Haematol 1991; 76, 251-255), of the demonstration in man of the combined effects of erythropoietin as an erythroid mitogen and vincristine as a mitotic blocker.
Leukemia 1992 Nov
PMID:Selective metaphasic arrest of erythroblasts by vincristine in patients receiving high doses of recombinant human erythropoietin for myelosuppressive anemia. 143 24

C57BL/6J murine bone marrow cells, infected with a retroviral vector (MP Zen) carrying a monkey erythropoietin cDNA, were transplanted into lethally irradiated syngeneic recipients to study the effect of erythropoietin production by hemopoietic cells. High levels of erythropoietin were recorded in the plasma (median value: 1.2 u/ml) and in media conditioned by peritoneal, spleen, and bone marrow cells from recipient mice. In transplanted mice, the hematocrit was elevated (90 +/- 5%) and the mice died at a mean of 71 days after transplantation. In the blood, platelet counts were usually low and nucleated blood cells slightly elevated. Spleen weight increased 5-fold and bone marrow cellularity decreased slightly. There was a 9.9-fold increase in erythroblast numbers, a 2-fold reduction of lymphocytes, and no variation of the myeloid cells when the total cellularity of bone marrow, spleen, peripheral blood, and peritoneal cells were considered. Calculation of the total numbers of progenitor cells in these organs revealed a 18-fold increase in erythroid colony-forming units (CFU-E) but no significant variation of the erythroid burst-forming units (BFU-E), and myeloid progenitor cell numbers. A variable proportion of CFU-E, (12% or 24% in bone marrow or spleen, respectively) was able to proliferate in unstimulated cultures. Erythropoietic amplification occurred in the spleen and there was a redistribution of the BFU-E and myeloid cells from the bone marrow to the spleen. No significant extramedullary erythropoiesis was seen. This study emphasizes the erythroid specificity of erythropoietin and shows that elevated dysregulated erythropoietin production by hemopoietic cells leads to a fatal polycythemia without erythroid neoplastic transformation.
Leukemia 1992 Feb
PMID:Fatal polycythemia induced in mice by dysregulated erythropoietin production by hematopoietic cells. 155 41

We attempted to develop a purification method for cell cycle-dormant murine multipotential progenitors that is simple and has a high recovery. Multilineage colony formation from mice that had been treated with 150 mg/kg 5-fluorouracil was assayed in cultures containing interleukin-3, interleukin-6, and erythropoietin. The cells with density 1.0631-1.0770 g/cm3 were approximately 40-fold enriched for multipotential progenitors. Negative immunomagnetic selection with a panel of lineage-specific monoclonal antibodies including anti-B220, anti-Gr-1, anti-Mac-1, anti-L3T4, and anti-Lyt-2 resulted in a cumulative 150-fold enrichment. When the density-separated and lineage-negative cells were further enriched by fluorescence-activated cell sorting with monoclonal antibody D7 (anti-Ly-6A/E), total enrichment averaged 800-fold and recovery was 17%. The method described here provides a relatively simple technique for the isolation of the multipotential progenitors and should be useful for the studies of regulation of hemopoiesis.
Leukemia 1992 Mar
PMID:Enrichment of murine marrow cells for progenitors of multilineage hemopoietic colonies. 156 55

Recombinant human erythropoietin (rhEpo) was given i.v. at a dose of 50 U/kg/tid to eight patients undergoing an HLA-matched, ABO-compatible bone marrow transplantation (BMT), from day +1 up to day +30. Compared to the data recorded in 13 similar BMT patients who had not received the hormone, the administration of rhEpo resulted in a faster erythroid engraftment: in fact, the time required to reach a stable hematocrit value greater than or equal to 35% decreased from 123.0 to 58.0 days after BMT. Moreover, the number of blood reticulocytes on day +21 was about fourfold greater in the rhEpo group than in the controls, while the number of the most immature, high RNA content reticulocytes (HFR), as determined by a flow cytometric technique, was more than sixfold greater; finally, the recovery time of both total and HFR reticulocytes was significantly reduced by rhEpo. The stimulation of erythroid progenitors also resulted in a reduction in red blood cell (RBC) transfusion requirements: the number of RBC units delivered in the first 30 days following BMT decreased from 8.1 in the controls to 4.0, while the total number of RBC units before transfusion independence was about threefold lower than in the control. Finally, the time of transfusion dependence was significantly shortened by rhEpo. No clinically significant adverse effect directly attributable to rhEpo was recorded. These data suggest that the administration of rhEpo may be beneficial in hastening erythroid engraftment, and possibly in reducing RBC transfusion requirements following BMT.
Leukemia 1992 Mar
PMID:Stimulation of erythroid engraftment by recombinant human erythropoietin in ABO-compatible, HLA-identical, allogeneic bone marrow transplant patients. 156 59

Nine patients with myelodysplastic syndromes and one patient with agnogenic myeloid metaplasia have been treated with recombinant human erythropoietin (rhEpo), at the dose of 150 U/kg/day. Although serum Epo levels were correlated with hemoglobin concentrations in the whole population of patients, they clearly appeared inadequate in some instances, if compared to those of a group of control subjects with iron deficiency anemia. Moreover, no correlation was found between serum Epo and reticulocytes. Six patients showed a partial or complete response to the treatment and the outcome was not correlated with the pre-therapy serum Epo levels; however, serum Epo was less than 100 mU/ml in three of four patients who achieved a complete response. The mechanism(s) by which Epo stimulated erythrocyte production in myelodysplastic patients is unclear, because the number of both the reticulocytes and erythroid progenitors remained unchanged during and at the conclusion of a three months' therapy. Further studies are needed to better define the optimal dosage required to correct anemia in myelodysplastic syndromes, and to clarify rhEpo mechanism of action in these diseases.
Leukemia 1992 Apr
PMID:Recombinant human erythropoietin for treatment of myelodysplastic syndromes. 158 94

In patients with hairy cell leukemia (HCL), we measured serum levels of monocyte colony-stimulating factor (M-CSF), interleukin-6 (IL-6), and erythropoietin during various degrees of pancytopenia characteristic for this disease. Serial sera from 12 HCL patients during various stages of the disease were analyzed. No correlation was found between the levels of M-CSF or IL-6 and the numbers of circulating monocytes or platelets, normal values of M-CSF (4 to 10 mg/l), and IL-6 (3-50 U/ml) being detected during all stages of the disease. In contrast, erythropoietin levels were inversely related with the hemoglobin concentration (r = -0.79), indicating the presence of a normal feedback mechanism for this factor in patients with HCL.
Leukemia 1992 Jul
PMID:Serum monocyte colony-stimulating factor, erythropoietin and interleukin-6 in relation to pancytopenia in hairy cell leukemia. 162 96

Hemopoietic growth factors are used with increasing frequency in the treatment of patients with myelodysplastic syndromes (MDS). While a response occurs regularly, it has not been unequivocally resolved whether this effect is due to the stimulation of normal hemopoiesis or to induced maturation of the abnormal clone. To determine whether selective responses to colony-stimulating factors of normal versus abnormal clones occurred, cytogenetic analysis was performed on bone marrow cells of MDS patients before and during in vivo treatment with granulocyte-macrophage colony-stimulating factor (GM-CSF) or recombinant human erythropoietin (rhEPO). A proliferation of additional clones could be demonstrated by karyotypic analysis in one patient during GM-CSF therapy and in two patients during rhEPO treatment. Two patients, initially with completely normal cytogenetics, developed a mixture of normal and abnormal metaphases during treatment. Two patients, initially with all abnormal metaphases, developed normal metaphases during treatment with GM-CSF. A mosaic of normal and abnormal metaphases was present in six patients. The percentage of abnormal metaphases increased in three patients during GM-CSF treatment, and in one patient during rhEPO therapy. The cytogenetic anomalies in one patient persisted after clinical response to treatment, suggesting that GM-CSF enhanced maturation of the abnormal clone. These data indicate that cytokine therapy in MDS may have diverse effects on hematopoiesis.
Leukemia 1992 Aug
PMID:Cytogenetic effects on cells derived from patients with myelodysplastic syndromes during treatment with hemopoietic growth factors. 164 Jul 27

The recently derived J2E cell lines differentiate in response to erythropoietin. However, during the course of growth in culture, a subclone has emerged which fails to synthesize hemoglobin or show accelerated proliferation following hormonal stimulation. The inability to respond to erythropoietin is not due to autocrine production of the hormone by these cells. Moreover, it appears unlikely that the block occurs at the level of the erythropoietin receptor as the number of receptors per cell was only marginally reduced and both ligand binding and internalization were normal. It is likely, therefore, that the intracellular signal transduction mechanism is faulty or a defect in hemoglobin production has developed.
Leukemia 1990 Jan
PMID:Evolution of a mutant J2E erythroid cell line which does not respond to erythropoietin. 168 37

The effects of recombinant human tumor necrosis factor alpha (TNF alpha) on colony growth were studied using highly enriched progenitor cells from normal human bone marrow. Supplementation of TNF to culture resulted in a dose-dependent suppression of granulocyte colony-stimulating factor (G-CSF) induced granulocytic colony formation and also erythropoietin (Epo) induced erythroid burst formation. However, the number of erythroid bursts, stimulated by interleukin-3 (IL-3) plus Epo, increased when TNF was added at comparable concentrations. Further, TNF enhanced eosinophilic colony growth induced by IL-3 or granulocytic-macrophage colony-stimulating factor (GM-CSF). In GM-CSF cultures TNF (100-1000 U/ml) also induced granulocytic and macrophage colonies. The addition of neutralizing antibodies against G-CSF, GM-CSF, or interleukin-6 (IL-6) to culture did not abrogate the observed effects of TNF, so that stimulation of myeloid colony growth was unlikely to result from the secondary induction of G-CSF or GM-CSF. TNF therefore exerts favourable effects on hematopoietic progenitors responsive to the more primitive colony-stimulating factors (IL-3, GM-CSF) and potent negative effects on precursors reactive to the single lineage G-CSF and Epo. These contrasting effects of TNF suggest that TNF, when available to marrow progenitors at similar tissue concentrations, may drive hematopoiesis within the progenitor cell compartment into selected directions.
Leukemia 1991 Jan
PMID:Positive and negative effects of tumor necrosis factor on colony growth from highly purified normal marrow progenitors. 170 38


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