Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026986 (myelodysplastic syndrome)
 14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A novel long-term cultured interleukin (IL)-3-dependent human myelodysplastic cell line, MDS92, was shown to contain several myeloid-lineage cells such as neutrophils, macrophages, eosinophils, and a small number of megakaryocyte-lineage cells. Therefore this cell line possesses at least bipotential characteristics of myeloid- and megakaryocyte-lineages. Granulocyte colony-stimulating factor clearly promoted the neutrophil alkaline phosphatase activity of MDS92 cells. To the contrary, the incidence and growth of CD41-positive cells were hardly affected by the addition of IL-6, IL-11, c-mpl ligand (thrombopoietin, TPO) or erythropoietin. TPO slightly supported the growth of CD34-positive cell fraction, but not CD41-positive cell fraction of MDS92 cells in combination with IL-3 or Steel factor. This cell line will be a useful tool for the study of MDS stem cells, but the mechanism of commitment of differentiation in MDS stem cells remains unknown.
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PMID:A novel factor-dependent human myelodysplastic cell line, MDS92, contains haemopoietic cells of several lineages. 854 20

The myelodysplastic syndromes (MDS) are a heterogeneous group of disorders characterized by peripheral blood cytopenias with a hypercellular bone marrow exhibiting dyspoiesis. The MDS range from those with a relatively indolent course (e.g., refractory anemia with or without ringed sideroblasts) to more aggressive disorders (e.g., refractory anemia with excess blasts [RAEB], and RAEB in transformation [RAEB-T]), which may exhibit a clinical course indistinguishable from acute myeloid leukemia (AML). Supportive care is the standard treatment for most patients, particularly those who are elderly, with the judicious use of blood components and antibiotics. For younger patients with RAEB and RAEB-T, antileukemic therapy might be considered, since the outcome is similar to that of patients with AML. Promising new chemotherapy agents currently in clinical trials include the topoisomerase I inhibitor, topotecan. The only curative treatment for MDS is allogeneic bone marrow transplantation, with long-term survival in approximately 40%, but with treatment-related deaths in 25%-40%. Factors predicting outcome include age, cytogenetics, number of blasts, and others. Myeloid growth factors (e.g., G-CSG, GM-CSF), increase the granulocyte count in most patients and may be useful in the setting of an active infection, although the prophylactic use of these agents does not improve survival. Erythropoietin increases the hematocrit in about 20% of patients. Growth factors being evaluated for their role in enhancing platelet counts include interleukin 11, stem cell factor, and megakaryocyte growth and development factor (thrombopoietin). Newer strategies to improve the outcome of patients with MDS should be based on an increased understanding of the biology of these disorders.
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PMID:The Myelodysplastic Syndromes. 1038 27

The myelodysplastic syndromes (MDS) are a heterogenous family of hematologic disorders characterized by ineffective hematopoiesis. Because of the variability between patients regarding prognosis and morbidity related to the disease, consensus regarding the management of these patients has been difficult. Over the past several years, new prognostic scoring systems such as the International Prognostic Scoring System (IPSS) have attempted to provide a projection for long-term stability of the percentage of patients who have "low-grade" or indolent MDS. Unfortunately, its lack of prospective use in clinical trials and other settings has thus far failed to validate it as a functional decision-making tool. Thus, investigators have hypothesized that separating patients based on more simplistic treatment-oriented guidelines may be more efficient. For the majority of patients with MDS, no curative option exists. Patients who are young enough and have an available matched sibling or matched unrelated donor may undergo an allogeneic bone marrow transplant (BMT) with a potential cure rate of 30% to 50%. The major issue regarding this approach is the relatively high morbidity and the risk that the patient's lives may be shortened, that their quality of life will be worsened, or that no overall benefit will occur (relapse). Compounding the issue of selection and timing for BMT is the fact that the best results in terms of relapse-free survival appear to be in the subset of patients with early or low-grade MDS, characterized by refractory anemia with or without ringed sideroblasts. For these patients, lacking a donor for BMT, the major issue has become the consideration of induction chemotherapy. While dose-intensive chemotherapy may improve outcome in a small percentage of patients, the majority of elderly patients with MDS are not optimal candidates for such an approach. As a result, supportive care has a major role for patients with MDS and depending on the French-American-British (FAB) presentation and comorbid illnesses may be the preferred approach. Erythropoietin, a growth factor, is perhaps the most commonly used supportive care after transfusion. The use of colony-stimulating growth factors to support leukopenia is currently under investigation. The use of thrombopoietic agents has lagged behind in the management of MDS patients. Investigation of interleukin-6 (IL-6), a thrombopoietic cytokine, showed some ability to increase platelets through significant toxicity. Investigation of IL-11, an approved thrombopoietic growth factor, is preparing to start and should aid in determining its role in this setting.
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PMID:Advances in supportive care of myelodysplastic syndromes. 1053 Jul 13

We investigated treatment with gemtuzumab ozogamicin (GO) in 51 patients aged 65 years or older with newly diagnosed acute myeloid leukemia (AML), refectory anemia (RA) with excess of blasts in transformation, or RA with excess blasts. GO was given in doses of 9 mg/m(2) of body-surface area on days 1 and 8 or, therapeutically equivalently, on days 1 and 15, with or without interleukin 11 (IL-11; 15 microg/kg per day on days 3 to 28), with assignment to IL-11 treatment made randomly. Complete remission (CR) rates were 2 of 26 (8%) for GO without IL-11 and 9 of 25 (36%) for GO with IL-11. Regression analyses indicated that IL-11 was independently predictive of CR but not survival. We compared GO with or without IL-11 with idarubicin plus cytosine arabinoside (IA), as previously administered, in similar patients. The CR rate with IA was 15 of 31 (48%), and survival was superior with IA compared with GO with or without IL-11 (P =.03). Besides accounting for possible covariate effects on outcome, we also accounted for possible trial effects (TEs) arising because IA and GO with or without IL-11 were not arms of a randomized trial. Bayesian posterior probabilities that GO with or without IL-11 produced longer survival than IA, after accounting for covariates and TEs, were less than 0.01 in patients with abnormal cytogenetic findings (AC) and less than 0.15 in patients with normal cytogenetic findings (NC). Regarding CR, the analogous probabilities were less than 0.02 for GO without IL-11 (all cytogenetic groups), and for GO with IL-11, less than 0.25 for AC groups and about 0.50 for NC groups. TEs 2 to 5 times the magnitude of those previously observed would be needed to conclude that survival with GO with or without IL-11 is likely longer than with IA. Thus, there is little evidence to suggest that GO with or without IL-11 should be used instead of IA in older patients with newly diagnosed AML or myelodysplastic syndrome.
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PMID:Gemtuzumab ozogamicin with or without interleukin 11 in patients 65 years of age or older with untreated acute myeloid leukemia and high-risk myelodysplastic syndrome: comparison with idarubicin plus continuous-infusion, high-dose cytosine arabinoside. 1203 60

5-azacytidine (AZA) yields hematologic improvement in patients with myelodysplastic syndromes (MDS). Ineffective hemopoiesis in MDS produce the paradox of high intramedullary cellularity with peripheral cytopenias. Leukemia inhibitory factor (LIF), oncostatin M (OSM), interleukin (IL)-6, and IL-11 regulate hemopoiesis and LIF, OSM, and IL-6 also inhibit the proliferation of myeloid leukemic cell lines through the signal-transducing subunit gp130. These IL-6-type cytokines were measured by enzyme-linked immunosorbent assay in cell culture supernatants (SN) obtained from peripheral blood mononuclear cells (MNC) and monocyte-depleted MNC of patients with refractory anemia (RA; n=12) and healthy individuals (n=10). AZA down-regulated OSM, IL-6, and IL-11 release by MNC of patients but not by MNC from healthy individuals. Patient's SN had significantly lower concentrations of LIF, OSM, and IL-11 than SN of normal subjects. When monocyte-depleted MNC of patients were stimulated with phytohemagglutinin a significant increment in OSM levels was observed. In contrast, monocyte depletion in healthy subjects did not cause any significant change in OSM values. We conclude that: (a) AZA inhibits the release of OSM, IL-6, and IL-11 exclusively in RA-diseased MNC, (b) Patient's MNC release subnormal amounts of LIF, OSM, and IL-11, and (c) RA-derived monocytes probably down-regulate OSM release by phytohemagglutinin-activated MNC.
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PMID:Effect of azacytidine in the release of leukemia inhibitory factor, oncostatin m, interleukin (IL)-6, and IL-11 by mononuclear cells of patients with refractory anemia. 1254 79

Recent progress in understanding the pathobiology of the myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) have led to the development of various immunologically oriented therapies for these diseases. The existence of elevated levels of tumor necrosis factor-alpha (TNF-alpha) in bone marrow during early stages of MDS, and the possibility that TNF- proportional, variant suppresses normal hematopoiesis led to studies of attempts to block the activity of TNF-alpha. An anti-TNF monoclonal antibody and an antibody comprised of the soluble extracellular ligand-binding portion of the TNF receptor have both been evaluated recently in several small pilot studies. The recognition that marrow suppression in MDS may, in part, be a T-cell mediated autoimmune process has stimulated various trials of antithymocyte globulin and other similar agents. Gemtuzumab ozogamicin, an antibody against CD33 conjugated to the cytotoxic agent calicheamicin, is approved for use in AML and is currently being investigated as a potential therapeutic agent in MDS. Clinical trials were conducted as either monotherapy or in combination with cytokines such as IL-11 and chemotherapeutic agents including idarubicin, fludarabine, and/or cytarabine. Other antibodies are being developed as immunoconjugates with radioisotopes as part of conditioning regimens prior to bone marrow transplantation for AML or MDS. These include (131)I-anti-CD45 antibody (BC8), (131)I anti-CD33 antibody (p67), (213)Bi-M195 antibody, and (188)Re-labeled anti-CD66 antibody. The clearest example of successful immunotherapy for MDS (and AML) is the use of the graft-versus-tumor effect associated with allogeneic hematopoietic cell transplantation. Recently, nonmyeloablative transplants have been explored with encouraging results. Vaccines using overexposed self-antigens such as WT1 and PR1 are other attempts to induce a T-cell mediated response against MDS.
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PMID:Immunobiologic therapies for myelodysplastic syndrome. 1549 1

In spite of recent advances in the treatment of myelodysplastic syndromes (MDS), supportive care remains a very important part of the therapy. Red blood cells transfusions are the most important component of this supportive care. They transiently relieve anemia symptoms and alleviate their effects on quality of life and daily functioning. Platelet transfusion therapy is less frequently needed, at least in low-risk MDS. Dealing with an increased risk of infections linked to neutropenia, mainly by broad spectrum antibiotics, is also needed, more often in advanced stages of [dict: MDS] or when the MDS evolves to acute myeloid leukemia. Chronic red blood cell transfusions expose patients to various side-effects, including blood components intolerance reactions and alloimmunization risks, but also increased frequency of iron overload, a more significant problem in low-risk heavily transfused MDS patients, who have prolonged life expectancy. The use of growth factors is becoming a more and more important part of current supportive care. High-dose erythropoietin is able to reduce or suppress red blood cell transfusions needs in selected subgroups of MDS. The short-term use of granulocyte colony-stimulating factor is also often proposed in infections, although not formally established by prospective trials. Although trials of growth factors with thrombopoeitic activity have been performed with interleukin 11 and are underway with thrombopoeitin, none of them are available for routine use.
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PMID:Supportive care including growth factors in myelodysplastic syndromes. 1602 1