Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mice with W mutations characterized by hypopigmentation, sterility, anemia, and mast cell deficiency have abnormalities in c-kit, a receptor with tyrosine kinase activity. Recently, the ligand for c-kit was cloned by investigators in several laboratories. Zsebo et al identified and cloned a gene for a cytokine termed stem cell factor (SCF) in the medium conditioned by buffalo rat liver cells, and this cytokine proved to be c-kit ligand. We have examined the effects of recombinant rat SCF (rrSCF) on colony formation from primitive hematopoietic progenitors in culture. rrSCF and erythropoietin (Ep) supported formation of granulocyte/macrophage (GM) colonies as well as a small number of multilineage and blast cell colonies from marrow cells of normal mice. We then examined the effects of rrSCF using marrow and spleen cells of mice that had been treated with 150 mg/kg 5-fluorouracil (5-FU). Unlike single factors, combinations of factors such as rrSCF plus interleukin-3 (IL-3), rrSCF plus IL-6, and rrSCF plus granulocyte colony-stimulating factor (G-CSF) markedly stimulated the growth of multilineage colonies. In contrast to these factor combinations and a combination of IL-3 and IL-6, a combination of rrSCF and IL-4 did not support multilineage colony formation. Mapping studies of the development of multipotential blast cell colonies further indicated that rrSCF, like IL-6, G-CSF, and IL-11, shortens the dormant period in which the stem cells reside. When we tested the effects of rrSCF using pooled blast cells, which are highly enriched for progenitors and are devoid of stromal cells, rrSCF plus Ep supported formation of only a few multilineage colonies, indicating that rrSCF itself is ineffective in support of the proliferation of multipotential progenitors. However, rrSCF supported formation of a significant number of neutrophil and neutrophil/macrophage colonies from pooled blast cells, indicating that rrSCF is able to support directly the proliferation of progenitors in neutrophil/monocyte lineages. c-kit ligand may play important roles in adult hematopoiesis.
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PMID:Enhancement of murine blast cell colony formation in culture by recombinant rat stem cell factor, ligand for c-kit. 171 19

Hematopoietic dysfunction with peripheral cytopenias is a common complication of human immunodeficiency virus (HIV) infection. Symptomatic anemia is the most common cytopenia and occurs in the presence and absence of myelosuppressive drug therapy such as zidovudine. Drug-induced neutropenia and immune thrombocytopenia are also frequent and occur in up to 50% of acquired immunodeficiency syndrome (AIDS) patients. Attempts to reduce the impact of bone marrow failure have focused on dose reduction of zidovudine, ganciclovir, and chemotherapy, and the use of recombinant hematopoietic hormones such as erythropoietin (EPO) and granulocyte colony-stimulating factor (G-CSF). Despite these maneuvers, approximately 30% of patients with AIDS receiving zidovudine will become transfusion-dependent. This has led to investigations of other cytokines that may increase blood cell formation. The recent identification of decreased number and proliferation of hematopoietic progenitors in patients with HIV infection suggests that agents which have activity on progenitor cell pools may have clinical utility. We demonstrate that human stem cell factor (HuSCF) increases burst-forming unit-erythroid (BFU-E), colony-forming unit-granulocyte-monocyte (CFU-GM), and CFU-Mix formation in vitro in normal and HIV-infected individuals. HuSCF also decreases the sensitivity of BFU-E to inhibition by zidovudine without altering HIV replication in lymphocytes or monocytes, altering peripheral blood mononuclear cell proliferation to phytohemagglutinin (PHA) and interleukin-2 (IL-2) or altering the effectiveness of zidovudine or dideoxyinosine in inhibiting HIV replication in lymphocytes or monocytes. These studies suggest that HuSCF may have clinical utility in HIV infection as an adjunctive treatment for HIV-related cytopenias.
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PMID:Potential use of human stem cell factor as adjunctive therapy for human immunodeficiency virus-related cytopenias. 172 Jun 98

Mouse strains carrying mutations at the Dominant White Spotting (W) locus or the Steel (Sl) locus are anemic and display defects in pigmentation and gametogenesis. In W mutants the anemia is due to a deficiency of hemopoietic stem cells and, in Sl mutants, to a deficiency of supporting stromal cells in the bone marrow. The W locus encodes the c-kit proto-oncogene product, a cell surface receptor with protein-tyrosine kinase activity, and the Sl locus encodes its ligand, a hemopoietic cytokine known variously as Steel factor (SLF), mast cell growth factor, stem cell factor, and Kit ligand. SLF can synergize with a number of other cytokines to stimulate growth of hemopoietic progenitors in vitro and stimulates blood cell production in vivo in animals. Here we review the biological activities of SLF, with particular emphasis on its effects on hemopoietic stem and progenitor cells. We also discuss present knowledge of the molecules involved in SLF-triggered signal transduction, and speculate on potential therapeutic applications for SLF in human disease.
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PMID:The kit receptor and its ligand, steel factor, as regulators of hemopoiesis. 172 56

Stem cell factor (SCF) promotes the growth of multilineage hematopoietic cells. SCF is a product of the steel (Sl) locus of the mouse, and it is a ligand for the c-kit proto-oncogene receptor. Previous studies have investigated the distribution of SCF mRNA in developing and adult tissues of the rat, including the brain. However, there have been conflicting reports on the distribution of SCF mRNA in adult rat brain. Specially noteworthy was one report of the absence of SCF mRNA in adult hippocampus, while another group reported the presence of that mRNA in the dentate gyrus of the hippocampus. We conducted this study to determine the precise localization of SCF mRNA in adult brain, and were especially interested in determining whether that mRNA is localized in adult hippocampus. We used in situ hybridization histochemistry to demonstrate that the gene encoding SCF is actively expressed in neuron-like cells in various regions of adult rat brain. Our data show that SCF mRNA is present in neuron-like cells in the thalamus, cerebral cortex, cerebellum, and hippocampus, particularly in the dentate gyrus, but also in CA1, CA2, and CA3. We did not localize SCF mRNA in glia-like cells. Dyskeratosis congenita is a severe human disorder, associated with dyskeratosis, anemia, and mental retardation. It has been postulated that dyskeratosis congenita is due to a deficiency in SCF function. It is unknown why patients with dyskeratosis congenita suffer from mental retardation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Localization of stem cell factor mRNA in adult rat hippocampus. 748 32

The immunomodulator AS101 has previously been found to induce mouse and human hematopoietic cells to secrete cytokines such as interleukin-1 alpha (IL-1 alpha), IL-2, tumor necrosis factor-alpha (TNF-alpha), and gamma interferon (IFN-gamma). The compound was shown to protect mice from lethal and sublethal effects of chemotherapy and irradiation. AS101 prevented the decrease in the number of bone marrow (BM) and spleen myeloid progenitor cells, and increased the survival of lethally treated mice. In this study, we show a dose-dependent response of AS101 in the induction of high secretion levels of IL-6, IL-3, granulocyte-macrophage colony-stimulating factor (GM-CSF), and stem cell factor (SCF). Since these growth factors are known to induce the proliferation and differentiation of multilineage progenitors, including megakaryocytic and erythroid progenitors, we designed this study to evaluate the role of AS101 in attenuating thrombocytopenia, anemia, and multilineage myelosuppression associated with chemotherapy. We demonstrate that pretreatment of mice with AS101 24 hours before intraperitoneal injection of 250 mg/kg cyclophosphamide (CYP) or intravenous injection of 150 mg/kg 5-fluorouracil (5-FU) significantly increased the number of circulating white blood cells (WBC) and platelets. The numbers of both neutrophils and lymphocytes were significantly increased in AS101-treated mice subjected to chemotherapy. In addition, AS101 attenuated erythropenia caused by 5-FU. It could also increase megakaryocyte and erythroid progenitor cells (CFU-MK and CFU-E) in the BM of treated mice severely affected by chemotherapy. We demonstrate that the protective effect of AS101 could be abrogated by treatment with anti-IL-1R or anti-SCF antibodies. We suggest that the endogenous production of cytokines such as IL-1, IL-6, IL-3, SCF, and GM-CSF in mice treated with AS101 offers protection to circulating blood elements and ameliorates the reconstitution of megakaryocytic and erythroid progenitors. The simultaneous protection by AS101 of multilineage cell compartments is probably due to stimulation by AS101 of a selective subpopulation of primitive stem cells resistant to chemotherapy. On the basis of these studies, phase II clinical trials with patients treated with chemotherapy in combination with AS101 have been initiated.
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PMID:Effect of the immunomodulator AS101 on chemotherapy-induced multilineage myelosuppression, thrombocytopenia, and anemia in mice. 749 64

Stem cell factor (SCF) is characterized by its capacity to synergize dramatically with other haemopoietic growth factors in in vitro erythroid, myeloid, and lymphoid progenitor culture systems. We have measured serum SCF concentrations by enzyme immunoassay in 85 patients with myelodysplasia (MDS). Serum samples were taken in 1988-89 and in 1991-92 and stored at -20 degrees C. Mean serum SCF concentration in the MDS patients was 2.81 ng/ml (range 0.6-8.0). This was significantly lower (P = 0.0001) than the values for 234 normal subjects; mean 3.30 ng/ml (range 1.3-8.0). No significant relationship between SCF concentration and peripheral blood counts, bone marrow parameters, red cell transfusion status, survival or FAB subtype was found, although a trend of decreasing SCF concentration from refractory anaemia through sideroblastic anaemia and chronic myelomonocytic leukaemia to refractory anaemia with excess blasts was seen. The reduced SCF serum concentration in some patients with myelodysplasia suggests a rationale for therapy with recombinant SCF in these patients.
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PMID:Serum stem cell factor concentration in patients with myelodysplastic syndromes. 750 11

Human recombinant stem cell factor (rSCF) was tested for its capability of improving the defective growth of hemopoietic progenitors in 28 cases of myelodysplastic syndromes (MDS). In vitro growth and response to rSCF were quite variable. However, in most cases, rSCF stimulated CFU-GM growth induced by rG-CSF, rGM-CSF, rIL-3, 5637 conditioned medium (50-1400% enhancement). rSCF effect was slightly more evident on day 14 CFU-GM and in the presence of rIL-3. BFU-E growth induced by rEPO or rIL-3 + rEPO was enhanced by rSCF in about 50% of cases, in linear correlation with the levels of patients' hemoglobin. rSCF did not increase CFU-E growth, whereas it slightly stimulated CFU-Mk in 33% of the cases. EPO, SCF and, particularly, their combination, enhanced the recovery of normal CFU-E and BFU-E after 7 days of liquid culture. This was less evident in cultures of MDS patients. Conversely, CFU-GM generation in long term liquid cultures, although highly variable, was stimulated by rSCF and, above all, by rSCF + rG-CSF, similarly to what was observed with normal bone marrow samples. SCF seems to enhance in vitro erythropoiesis only in MDS cases presenting without severe anemia. It has little effect on megakaryocytopoiesis, while it seems to be more active on CFU-GM growth and maintenance.
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PMID:Stem cell factor improvement of proliferation and maintenance of hemopoietic progenitors in myelodysplastic syndromes. 750 32

Recombinant cytokines such as stem cell factor (SCF) are currently being tested for the ability to ameliorate 3'azido-3'deoxythymidine (AZT)-induced anemia in AIDS patients. Recently, we showed that SCF greatly increased burst-forming units-erythroid (BFU-E) but failed to increase hematocrits of AZT-treated immune-deficient (MAIDS) mice. We reasoned that hemin, previously shown to both enhance BFU-E proliferation and accelerate erythroid maturation, might bring about differentiation of this large SCF-induced pool of BFU-E and further protect BFU-E from AZT's toxic effect. We therefore studied, in vitro, the effect of combinations of hemin and SCF on growth of BFU-E from MAIDS mice. Hemin, at concentrations of 10 to 100 microM, ameliorated the growth-inhibitory effect of AZT. 50 microM hemin increased the ED50 of AZT from 1 x 10(-7) M to 1.7 x 10(-6) M. SCF also ameliorated AZT-induced toxicity, but to a lesser extent. SCF and hemin increased the number of BFU-E colonies observed in the presence of AZT in an additive fashion. The resistance of BFU-E to AZT's cytotoxic effect was greater in cultures receiving hemin and SCF together than in cultures receiving SCF or hemin alone. Zinc and tin protoporphyrins (Zn and Sn PP) increased the numbers of BFU-E observed. However, neither zinc nor tin protoporphyrins increased the ED50 of AZT. Combinations of SCF and hemin may prove useful in ameliorating AZT toxicity in both immune-suppressed mice and human immunodeficiency virus (HIV)-infected patients.
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PMID:Amelioration of azidothymidine-induced erythroid toxicity by hemin and stem cell factor in immune-suppressed mice. 751 46

Circulating haemopoietic progenitor cells from premature infants were assessed for their ability to respond to interleukin 3, granulocyte-macrophage colony stimulating factor and stem cell factor (SCF) in vitro. All three cytokines increased the number of colonies derived from burst forming units erythroid (BFU-E), colony forming units granulocyte-macrophage (CFU-GM) and multi-lineage progenitors (CFU-Mix) grown in the presence of erythropoietin (Epo). The size and haemoglobin content of BFU-E derived colonies also increased in the presence of the cytokines. Of those tested, SCF was found to be the most potent additive to Epo for the enhanced growth of BFU-E and CFU-Mix. In short-term liquid cultures without Epo, SCF alone induced globin synthesizing cells. Progenitors from premature infants were at least as responsive to all three cytokines as those from healthy adults. The use of SCF in combination with Epo in the prevention or treatment of anaemia in premature infants warrants further investigation.
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PMID:The in vitro effects of stem cell factor, interleukin 3 and granulocyte-macrophage colony stimulating factor on haemopoietic progenitor cells from premature infants. 751 35

We examined the combined effects of stem cell factor (SCF), or interleukin-3 (IL-3) with erythropoietin on the development of haemopoietic progenitors in 19 patients with aplastic anaemia (AA) and eight normal controls by using an in vitro clonal assay. SCF significantly enhanced the growth of total erythroid colonies (erythroid bursts, mixed colonies) in 11 patients and all normal controls, whereas IL-3 did so in only three patients. The number of SCF- or IL-3-dependent erythroid colonies was substantially lower in AA patients than in the controls. Comparison of the capacity of SCF and IL-3 to increase total erythroid colony growth indicated that half of the AA patients responded more strongly to SCF than the normal controls, while few patients responded in such a manner to IL-3. These findings suggest that SCF in vivo will have a more dramatic effect than IL-3 in improving anaemia in patients with AA.
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PMID:Stem cell factor enhances the growth of primitive erythroid progenitors to a greater extent than interleukin-3 in patients with aplastic anaemia. 752 18


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