UMLS:C0002871 - FACTA Search

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Query: UMLS:C0002871 (anemia)
52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Erythropoiesis is the process leading to the formation of red cells. Our understanding of erythropoiesis regulation has been due to the characterization of the erythroblast progenitor cells BFU-E and CFU-E. These cells cannot be recognized morphologically, but they proliferate and differentiate in vitro under the effect of growth factors. They correspond to different steps in erythroblast differentiation which is in fact subjected to different regulations. BFU-E cells are the earliest cells of erythropoiesis and are regulated by such growth factors as GM-CSF, Il-3 or Il-9, which are not specific to erythropoiesis. As they differentiate, the BFU-E cells become sensitive to erythropoietin, the erythropoiesis-specific hormone secreted mainly by the kidney in response to hypoxia. The action of erythropoietin and that of other growth factors are synergistically reinforced by a non erythropoiesis-specific growth factor called Steel factor which plays a very important physiological role since defects in its synthesis caused by genetic anomalies produce a lethal anaemia in mice. CFU-E cells, which precede proerythroblasts, are the most sensitive to the action of erythropoietin both in vitro and in vivo. A better knowledge of erythropoiesis regulation mechanisms should help us in the understanding of the physiopathology of some congenital or acquired diseases, such as erythroblastopenia or polycythaemia vera.
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PMID:[Erythropoiesis and its regulation]. 823 79

3'-azido-3'-deoxythymidine (AZT), the main antiviral drug used in AIDS treatment, is known to induce anemia and neutropenia. These effects have been attributed to its toxicity to hematopoietic progenitors. In this report, we present a new approach to reduce AZT hematotoxicity by using an inhibitory factor of the hematopoietic stem cells, the tetrapeptide AcSerAspLysPro (AcSDKP, Seraspenide), which has been shown to increase the survival of mice subjected to high doses of chemotherapy and to block reversibly the cycling of human granulocyte-macrophage colony forming unit (CFU-GM) and burst forming unit erythroid (BFU-E) progenitors. Normal bone marrow mononuclear cells (BMMNC) from 14 subjects were incubated with or without AcSDKP (10(-10) M) for 20 h and with or without AZT (100 microM) for another 2 h. After washing, cells were plated in methylcellulose in the presence of interleukin 3 (IL-3), granulocyte-macrophage colony stimulating factor (GM-CSF) and erythropoietin (EPO). Under these conditions, the preincubation of cells with AcSDKP reduced significantly the toxicity of AZT to both BFU-E and CFU-GM at least in 3 out of 8 and 4 out of 10 cases, respectively. A careful statistical analysis of these observations indicates that AcSDKP may be an efficient factor in preserving progenitors against AZT-induced hematopoietic toxicity.
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PMID:The tetrapeptide AcSerAspLysPro (Seraspenide), a hematopoietic inhibitor, may reduce the in vitro toxicity of 3'-azido-3'-deoxythymidine to human hematopoietic progenitors. 824 56

Because GM-CSF possesses burst-promoting activity (BPA) and megakaryocyte colony-stimulating activity (Meg-CSF) as well as stimulating activity on granulocyte-macrophage progenitors, and erythropoietin (Epo) has thrombopoietin-like activity, the combination therapy of GM-CSF and Epo seems to be more effective for stimulating erythropoiesis and thrombocytopoiesis in patients with pancytopenia. For this reason, the combination therapy of recombinant human GM-CSF (rhGM-CSF) and rhEpo was performed in two patients with refractory anemia (RA) and aplastic anemia (AA). Epo-unresponsive anemia was remarkably improved by adding rhGM-CSF to Epo and the effect lasted for 1 1/2 months in a patient with RA, but severe anemia occurred again immediately after the discontinuation of Epo. The neutralizing antibodies against GM-CSF were not demonstrated at the phase when anemia re-progressed in this patient. In a patient with AA, anemia and thrombocytopenia, which were refractory to previous administration of rhGM-CSF, responded to the combined administration of GM-CSF and Epo. Although the effects were maintained for 3 1/2 months, the anemia and thrombocytopenia became worse again after the administration of rhGM-CSF was changed from daily to every other day. These findings suggest the usefulness of combination therapy of GM-CSF and Epo for patients with pancytopenia.
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PMID:Combination therapy with rhGM-CSF and rhEpo for two patients with refractory anemia and aplastic anemia. 824 8

The effect of recombinant human erythropoietin (rhEPO) and interleukin 3 (IL3) on circulating haematopoietic progenitors consisting mainly of immature burst-forming-units-erythrocytes (BFU-E), was investigated in ten paediatric patients treated by regular haemodialysis. During a 30-week study rhEPO treatment resulted in a rise of median haemoglobin levels from 6.7 g/dl to > 10 g/dl in all patients. Before initiating rhEPO treatment the number of circulating BFU-E in chronic renal failure patients responded to grading doses of rhEPO in vitro similar to that in control children; however, the dose-response curves were not predictive for the in vivo response to rhEPO. After an initial rise in five patients BFU-E numbers declined by week 30 of rhEPO treatment. BFU-E numbers decreased to 35% of pretreatment values. The number of granulocyte-macrophage colony forming cells (GM-CFC) also decreased during rhEPO treatment. Addition of IL3 to the culture medium containing saturating concentrations of granulocyte-macrophage colony stimulating factor did not stimulate BFU-E numbers of patients before rhEPO treatment or those of controls. However, 2 weeks after start of rhEPO treatment IL3 increased the growth of patient's BFU-E in vitro to 220% of pretreatment levels, followed by a gradual decrease of stimulation until the end of observation. These findings indicate that: (1) long-term recruitment of circulating haematopoietic progenitors during rhEPO treatment is low in children with renal anaemia; (2) rhEPO sensitivity of circulating BFU-E is not predictive for the in vivo response; (3) rhEPO treatment results in enhanced sensitivity of BFU-E to IL3.
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PMID:Circulating haematopoietic progenitors during treatment of renal anaemia with recombinant human erythropoietin. 831 24

15 patients with small-cell lung cancer were treated with an "accelerated" chemotherapy consisting of standard-dose cyclophosphamide-doxorubicin-etoposide administered every 15 days (as opposed to the usual 21-day intervals) along with granulocyte-macrophage colony stimulating factor (10 micrograms/kg/day) administered prophylactically subcutaneously from day 4 to 13. The primary objective of this study was to examine the possibility of achieving a 50% dose-intensity increase by a shortening of chemotherapy intervals. 9 patients were not able to complete the planned six courses of chemotherapy owing to cumulative haematological toxicity. In fact, while leukopenia was acceptable and constant during treatment, both thrombocytopenia and anaemia progressively worsened with subsequent courses, becoming particularly severe after the 4th cycle when interruption of the treatment was often required. 13 patients who completed four courses of chemotherapy received a median of 96% of the planned dose-intensity. This corresponded with an average relative dose-intensity actually delivered of 1.44 compared with the planned dose-intensity of a standard cyclophosphamide-doxorubicin-etoposide every 21 days. In conclusion, acceleration of cyclophosphamide-doxorubicin-etoposide chemotherapy combined with granulocyte-macrophage colony stimulating factor can lead to a significant increase of dose-intensity but it is feasible only for a limited number of courses.
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PMID:High dose-intensity chemotherapy, with accelerated cyclophosphamide-doxorubicin-etoposide and granulocyte-macrophage colony stimulating factor, in the treatment of small cell lung cancer. 838 70

Cyclic neutropenia is the most frequent of the cyclic haematopoietic disorders characterized by its regular 21 d cyclic fluctuations in the number of blood neutrophils, and in many cases simultaneous fluctuations in the other blood cell lines. In this paper we describe a 77-year-old woman with a cyclic pancytopenia including all the myeloid cell lines and to some extent the lymphocytes with a constant and predictable oscillation period of about 100 d. Serial bone marrow biopsies and plasma lactoferrin measurements indicated a similar fluctuating pattern in the bone marrow production of neutrophils. Serial measurements of plasma GM-CSF concentration pointed at a simple feed-back inhibitory system. The condition was present for at least 4 years, after which it gradually improved, although the thrombocyte count still showed a fluctuating tendency after a further 4 years of observation. The clinical consequences were mild symptoms of anaemia and a few episodes of respiratory infections occurring during pancytopenic periods. We think this is the first case described in the literature with this variant of a cyclic haematopoietic disorder. The precise pathophysiological mechanism behind this condition is obscure, but probably it is due to a regulatory disturbance at a very early step in the haematopoietic stem cell hierarchy.
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PMID:Reversible adult-onset cyclic haematopoiesis with a cycle length of 100 days. 845 64

Seven patients, 3 men and 4 women 48-72 years of age and suffering from idiopathic myelofibrosis were given a combination of recombinant human erythropoietin (r-hu-Epo), interferon-alpha-2b (IFN) and GM-CSF, in an attempt to treat their pancytopenia and marrow fibrosis. The dose of r-hu-Epo was 200 U/kg 3 times weekly, that of IFN was 3 x 10(6)/U 3 times weekly, and that of GM-CSF was 250 micrograms/m2/daily. The duration of therapy ranged from 3 to 6 months for r-hu-Epo and IFN and was 3 weeks for GM-CSF. The treatment regimen had a beneficial effect on all patients. The levels of hemoglobin increased in all patients but particularly in 5 (2 of whom had been dependent on red blood cell transfusions). Splenomegaly decreased significantly in 4 patients. Fibrosis in the bone marrow decreased in 2 patients. Three patients also had an increase in the number of white blood cells during the therapy with GM-CSF. We observed mild side effects in 6 of our patients. One patient had severe side effects from IFN and treatment was discontinued. In conclusion, the combination of r-hu-Epo, IFN and GM-CSF may improve the anemia (due to r-hu-Epo), increase the white blood cell count (due to GM-CSF) and reduce the marrow fibrosis (probably due to IFN) in patients with idiopathic myelofibrosis.
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PMID:Combination therapy with recombinant human erythropoietin, interferon-alpha-2b and granulocyte-macrophage colony-stimulating factor in idiopathic myelofibrosis. 870 5

We have previously demonstrated that continuous administration of dose-escalation zidovudine (AZT) in either normal or LP-BM5 MuLV immunodeficient virus-infected mice (MAIDS) was associated with the development of anemia, neutropenia, and thrombocytopenia. Hematopoietic growth factors/cytokines are being evaluated to determine their efficacy in ameliorating the hematopoietic toxicity associated with AZT. In normal mice receiving AZT, an increase in only plasma erythropoietin and not GM-CSF, Meg-CSF or TNF-alpha has been reported. This article describes studies that investigated the effect of combination interleukin-3 (IL-3) and granulocyte-macrophage colony stimulating factor (GM-CSF) administered in normal non-viral, viral-infected, and viral-infected C57BL6 mice receiving dose-escalation AZT, i.e. 0.1 mg/ml, 1.0 mg/ml, and 2.5 mg/ml placed in the drinking water. Non-viral control mice responded to IL-3/GM-CSF by increasing erythropoiesis, myelopoiesis and platelet production measured by increased bone marrow and spleen derived erythroid, myeloid and platelet precursor stem cells cultured in semi-solid media. Virus-infected control mice not receiving IL-3/GM-CSF developed pancytopenia. Administration of IL-3/GM-CSF to virus-infected mice receiving dose-escalation AZT did not ameliorate the peripheral pancytopenia associated with immunodeficiency disease and AZT treatment, even though erythroid, myeloid and platelet precursor progenitor cells were increased at certain times when compared to either normal or viral-infected mice receiving IL-3/GM-CSF. These results indicate that the combination use of IL-3 and GM-CSF in vivo is only a partially effective growth factor/cytokine treatment to ameliorate the hematopoietic toxicity associated with the use of the anti-viral drug zidovudine.
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PMID:Effect of combination interleukin-3 (IL-3) and granulocyte-macrophage colony stimulating factor (GM-CSF) on hematopoiesis administered to retrovirus-infected immunodeficient mice receiving dose-escalation zidovudine (AZT). 878 16

Myeloid cells arise from a common stem cell whose development is regulated by stimulatory and inhibitory growth factors. Pluripotential hematopoietic stem cells are most influenced by IL-3, GM-CSF, and stem cell factor while committed progenitor cells are regulated by variable concentrations of GM-CSF, G-CSF, M-CSF, IL-5, Epo, and Tpo. As a result of their common origin, a key point to remember about myeloproliferative disorders is the involvement of multiple cell lines in dysplastic and neoplastic conditions. Dysplastic changes may signal early neoplastic changes with cases progressing to acute leukemia. Myelodysplastic syndrome (MDS) is associated with anemia or multiple cytopenias, normal to hypercellular bone marrow, ineffective hematopoiesis, and less than 30% blast cells of all nucleated cells in the bone marrow. Chronic myeloid leukemias also have less than 30% blast cells of all nucleated cells in the bone marrow and are distinguished from MDS by elevated cell counts of one or more cell lines with mature forms predominating. Acute myeloid leukemias, often the end result of all myeloproliferative disorders, are recognized by equal or greater 30% blast cells of all nucleated cells in the bone marrow. Additional diagnostic information from cytochemical stains, immunohistochemical staining, and cytogenetic analysis can influence the final diagnosis when morphology alone is equivocal. In conclusion, prognosis and response to treatment are best determined by application of a uniform set of standards in evaluating hematolymphatic neoplasia. Critical to diagnosis are complete blood and bone marrow evaluations including observation for dysplastic changes and blast cell quantitation. In addition, evidence for tissue infiltration identified through cytologic or histologic evaluations of lymph node, spleen, or liver is recommended.
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PMID:Myelopoiesis and myeloproliferative disorders. 886 89

The normal proto-oncogene c-fms encodes the macrophage growth factor (M-CSF) receptor involved in growth, survival, and differentiation along the monocyte-macrophage lineage of hematopoietic cell development. A major portion of our research concerns unraveling the temporal, molecular, and structural features that determine and regulate these events. Previous results indicated that c-fms can transmit a growth signal as well as a signal for differentiation in the appropriate cells. To investigate the role of the Fms tyrosine autophosphorylation sites in proliferation vs. differentiation signaling, four of these sites were disrupted and the mutant receptors expressed in a clone derived from the myeloid FDC-P1 cell line. These analyses revealed that: (1) none of the four autophosphorylation sites studied (Y697, Y706, Y721, and Y807) are essential for M-CSF-dependent proliferation of the FDC-P1 clone; (2) Y697, Y706, and Y721 sites, located in the kinase insert region of Fms, are not necessary for differentiation but their presence augments this process; and (3) the Y807 site is essential for the Fms differentiation signal: its mutation totally abrogates the differentiation of the FDC-P1 clone and conversely increases the rate of M-CSF-dependent proliferation. This suggests that the Y807 site may control a switch between growth and differentiation. The assignment of Y807 as a critical site for the reciprocal regulation of growth and differentiation may provide a paradigm for Fms involvement in leukemogenesis, and we are currently investigating the downstream signals transmitted by the tyrosine-phosphorylated 807 site. In Fms-expressing FDC-P1 cells, M-CSF stimulation results in the rapid (30 sec) tyrosine phosphorylation of Fms on the five cytoplasmic tyrosine autophosphorylation sites, and subsequent tyrosine phosphorylation of several host cell proteins occurs within 1-2 min. Complexes are formed between Fms and other signal transduction proteins such as Grb2, Shc, Sos1, and p85. In addition, a new signal transduction protein of 150 kDa is detectable in the FDC-P1 cells. The p150 is phosphorylated on tyrosine, and forms a complex with Shc and Grb2. The interaction with Shc occurs via a protein tyrosine binding (PTB) domain at the N-terminus of Shc. The p150 is not detectable in Fms signaling within fibroblasts, yet the PDGF receptor induces the tyrosine phosphorylation of a similarly sized protein. In hematopoietic cells, this protein is involved in signaling by receptors for GM-CSF, IL-3, KL, MPO, and EPO. We have now cloned a cDNA for this protein and found at least one related family member. The related family member is a Fanconia Anemia gene product, and this suggests potential ways the p150 protein may function in Fms signaling.
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PMID:Growth and differentiation signals regulated by the M-CSF receptor. 898 70

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