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)

The colony-stimulating factors (CSF) are a class of glycoprotein hormones that regulate the production and function of blood cells. Human sequences encoding four of the factors active on myeloid cells--granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), macrophage colony-stimulating factor (M-CSF), and interleukin-3 (IL-3)--have been molecularly cloned and the biosynthetic (recombinant) products introduced into clinical trials. Sufficient clinical data have accumulated regarding G-CSF and GM-CSF to allow insight into their potential use in clinical practice. Both molecules have shown some impact in the prevention of chemotherapy-induced neutropenia and in the treatment of cytopenias associated with myelodysplastic syndromes and aplastic anemia. G-CSF has shown promise in the treatment of congenital and idiopathic neutropenias.
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PMID:The colony-stimulating factors: biology and clinical use. 214 19

An increasing amount of data provides strong evidence for the complex multifactorial control of primary hemopoietic functions. Here we present a new multicellular functional unit, the Hematon, isolated from the light-density floating fraction of normal human bone marrow (BM) aspirates. The Hematon is organized in a compact, three-dimensional spheroid complex from central adipocytes, fibroblastoid cells, and resident macrophages that compartmentalize myeloid, erythroid, and megakaryocyte progenitor cells and their progenies. The Hematon fraction is more than twofold more abundant in progenitor cells when compared to the mononuclear cell (MNC) fraction as gauged by cytological techniques and by analysis of granulocyte-macrophage colony-forming unit (GM-CFU) populations. Individual Hematons may produce, within 2-3 weeks, up to 50,000 hemopoietic cells of different cell lineages in organotypic microcultures. Recombinant human hematopoietic growth factors interleukin 3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), and macrophage colony-stimulating factor (M-CSF) significantly stimulated the endogenous cell production of some but not all of the individually treated Hematons, indicating the heterogeneity of factor-responsive cells within the Hematon population. Comparative observations of 184 BM aspirates support the hypothesis that the presence of Hematons in a BM aspirate correlates positively with homeostatic blood cell production, because the Hematon was present in normal BM (31/40) and it was rare among patients with myelodysplastic syndromes (15/53), acute myeloblastic leukemia (7/39), and chronic myelocytic leukemia (5/52). We suggest that the Hematon represents a unifying model around which the variability of fundamental BM functions and dysfunctions can be explored.
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PMID:Hematon, a multicellular functional unit in normal human bone marrow: structural organization, hemopoietic activity, and its relationship to myelodysplasia and myeloid leukemias. 218 30

A 72-year-old man was admitted to our hospital because of general malaise. The peripheral blood showed pancytopenia (WBC 800/microliters, RBC 970,000/microliters, Plt 95,000/microliters). The bone marrow smear revealed morphological abnormalities in three lineage without increase in blasts. He was diagnosed as having myelodysplastic syndrome (MDS). He was treated with recombinant human granulocyte colony-stimulating factor (rhG-CSF) for leukopenia, and with washed RBC transfusions for anemia. Eight months after diagnosis of MDS, blastic cells increased in peripheral blood and bone marrow showing overt leukemic state. He died of pneumonia. An autopsy revealed that atypical megakaryocytes increased in bone marrow and infiltrated into the spleen and liver. This case suggests that not only blasts but also megakaryocytes infiltrate into extramedullary organs in some cases of MDS.
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PMID:[Atypical infiltration of megakaryocytes into the liver and spleen in a case of refractory anemia]. 221 79

The major hematopoietic growth factors have been produced through recombinant DNA technology and have entered initial clinical trials; results of these trials will be reviewed here. Granulocyte colony-stimulating factor (G-CSF) has been tested in patients with bladder cancer and small-cell carcinoma of the lung. In these studies, G-CSF ameliorated the leukopenia associated with combination chemotherapy, reduced the incidence of mucositis in the bladder cancer patients, and nearly eliminated the occurrence of serious infections in the lung cancer patients. Trials involving another factor, granulocyte macrophage colony-stimulating factor (GM-CSF), have resulted in a marked increase in white blood cell (WBC) counts in patients with myelodysplastic syndromes, and has accelerated the appearance of leukocytes and platelets after autologous bone marrow transplants. GM-CSF can also increase the WBC counts in acquired immunodeficiency syndrome patients treated with zidovudine. Both G-CSF and GM-CSF may produce multilineage effects in certain clinical settings and dose ranges. Finally, interleukin-1 (IL-1) and IL-3, which commit very early stem cells to a myeloid pathway, may be used in combination with G-CSF or GM-CSF to produce a synergistic response to various clinical situations.
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PMID:Status of colony-stimulating factors in cancer and AIDS. 240 93

Two cases of myelodysplastic syndrome (MDS) were treated with recombinant human granulocyte colony-stimulating factor (rhG-CSF). In both cases, an increase of peripheral neutrophil counts was noted with a peak within 12 hr after the rhG-CSF administration. Neutrophils with ring shaped or hypersegmented nuclei were noted in the peripheral blood during the treatment, and they disappeared promptly after discontinuation of the therapy. The results indicate that the rhG-CSF might have mobilizing and differentiating effects on neutrophils derived from the MDS clone.
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PMID:Morphologic changes of neutrophils in myelodysplastic syndrome treated with recombinant human granulocyte colony-stimulating factor. 245 90

In order to better understand the patho-physiologic role of granulocyte colony-stimulating factor (G-CSF), we estimated its serum levels in healthy persons and patients with various disorders, using a newly developed enzyme immunoassay (Motojima et al). In 49 of 56 normal healthy persons (88%), the levels were beneath the sensitivity of the assay (less than 30 pg/mL), while in the remaining seven healthy persons, the levels ranged from 33 to 163 pg/mL. On the other hand, nine of 11 patients (82%) with idiopathic aplastic anemia (AA), one patient with Fanconi's anemia, six of 12 patients (50%) with myelodysplastic syndrome (MDS), five of 12 patients (42%) with acute leukemia without any blast cells in the blood (M4: one, M5: one, L1: one, and L2: two), six of 18 patients (33%) with chronic myeloid leukemia (CML), one of two patients with chronic lymphoid leukemia (CLL), two of four patients with lung cancer, one patient with cyclic neutropenia, two of seven patients with malignant lymphoma, and four patients with acute infection had G-CSF levels ranging from 46 pg/mL to greater than 2,000 pg/mL. Interestingly, a reverse correlation between blood neutrophil count and serum G-CSF level was clearly demonstrated for aplastic anemia (r = -.8169, P less than .01). Moreover, it was found that the G-CSF level rose during the neutropenic phase of cyclic neutropenia and after chemotherapy or bone marrow transplantation (BMT) in three patients with leukemia; also high G-CSF levels were positively correlated to blood neutrophil counts in some cases of infectious disorders and lung cancer. The cellular sources and the mechanisms for production and secretion of circulating G-CSF were not investigated in this study, but the data presented here strongly indicate that G-CSF plays an important role as a circulating neutrophilopoietin.
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PMID:Serum granulocyte colony-stimulating factor levels in healthy volunteers and patients with various disorders as estimated by enzyme immunoassay. 246 34

[3H]thymidine uptake by NFS-60 cells in microcultures was found to increase in a linear fashion with the increasing doses of purified recombinant human granulocyte colony-stimulating factor (rhG-CSF). Such increases were found neither with rhG-CSF samples pretreated with rabbit anti-rhG-CSF serum nor with other human colony-stimulating factors such as granulocyte-macrophage colony-stimulating factor (hGM-CSF) or macrophage colony-stimulating factor (hM-CSF). Based on these findings, sera from normal persons and patients with severe infections or various hematological disorders were tested after dialysis using this system in order to determine whether G-CSF levels in sera can be estimated or not. In ten normal persons, five patients with acute myelogenous leukemia (AML M1, M2, and M3), five with myelodysplastic syndrome, and four with chronic myelogenous leukemia, no increases in [3H]thymidine uptake were found within the dose range of 0.4 microliters to 50 microliters. In contrast, linear dose responses parallel to a G-CSF standard curve were observed in one patient with a severe bacterial infection, four with aplastic anemia, two with acute myelomonocytic leukemia (AMMoL) (M4), and two with idiopathic neutropenia tested. From the standard curve, the probable levels of G-CSF were calculated as follows: approximately 200 pg/ml with infection, 130-220 pg/ml with aplastic anemia, 150 and 200 pg/ml with AMMoL, and 1120 and 1200 pg/ml with idiopathic neutropenia. The activities of sera were reduced by the anti-rhG-CSF serum pretreatment in the same way as documented in the case of rhG-CSF. Furthermore, the level in a patient with a severe infection became undetectable soon after elimination of the infection and blood neutrophil counts had returned to normal. These findings indicate that the microbioassay system will be useful for measuring circulating G-CSF levels which would fluctuate in accord with requirements for stimulating neutrophil production or with abnormal production of hG-CSF.
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PMID:A new bioassay for human granulocyte colony-stimulating factor (hG-CSF) using murine myeloblastic NFS-60 cells as targets and estimation of its levels in sera from normal healthy persons and patients with infectious and hematological disorders. 246 30

The myeloid growth factors are a promising new class of therapeutic agents with the potential for broad clinical application. Four recombinant myeloid growth factors, granulocyte macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), macrophage colony-stimulating factor (M-CSF), and interleukin (IL)-3 are available for clinical trials. GM-CSF has been studied in leukopenia related to acquired immunodeficiency syndrome (AIDS), aplastic anemia, and myelodysplasia, as well as in patients receiving chemotherapy and those undergoing autologous bone marrow transplantation. In these trials, GM-CSF was demonstrated to increase the number of neutrophils, eosinophils, and monocytes with corresponding bone marrow changes. Toxicity is dose-related, and maximum tolerated dosages are in the range of 16 to 32 micrograms/kg/day. The effects of daily subcutaneous administration of GM-CSF appear to be similar to those of intravenous (IV) administration. G-CSF, studied mainly in the treatment of neutropenia following cytotoxic chemotherapy, was found to decrease the duration of severe neutropenia as well as the risk of infections. G-CSF causes prominent increases in neutrophil levels without affecting eosinophils or monocytes. Associated toxicity is minimal, and subcutaneous administration is efficacious. Preliminary evidence suggests that G-CSF may also have a therapeutic role in indolent lymphoid neoplasms complicated by neutropenia. Administration of natural M-CSF to patients receiving chemotherapy and those with chronic childhood neutropenia has shown modest neutrophil increases. Preclinical data on IL-3 suggest that this agent increases neutrophils, eosinophils, basophils, reticulocytes, and possibly platelets.
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PMID:Clinical applications of the myeloid growth factors. 247 Dec 74

The peripheral blood morphologic findings in 17 patients with cancer who had received high-dose cytotoxic chemotherapy followed by recombinant human-granulocyte colony-stimulating factor (rh-GCSF) were reviewed and compared with a control group of patients who received only high-dose chemotherapy. Both groups showed dysmyelopoiesis (abnormal granulation and nuclear lobulation) in the granulocytic series during the period of bone marrow recovery that followed the cytotoxic chemotherapy. Most of these morphologic abnormalities were more prominent in the rh-GCSF-treated group. Monocytic cells in both groups showed prominent vacuolation and immature nuclei. The percentages and absolute numbers of large granular lymphocytes were increased in the rh-GCSF group compared with the control group. No quantitative or qualitative abnormalities of eosinophilic or basophilic granulocytes were detected in either group. Both groups showed nonspecific red blood cell abnormalities, and large platelets were present in half of the control group smears. This report provides the first detailed peripheral blood morphologic description in patients treated with rh-GCSF and high-dose chemotherapy.
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PMID:Peripheral blood morphologic changes after high-dose antineoplastic chemotherapy and recombinant human granulocyte colony-stimulating factor administration. 247 27

Recombinant DNA technology has allowed for the production of large quantities of several hematopoietic growth factors as cloned gene products. Three of these factors--recombinant human erythropoietin (r-HuEPO), granulocyte macrophage colony-stimulating factor (GM-CSF), and granulocyte colony-stimulating factor (G-CSF)--are currently undergoing clinical trials and appear to offer considerable promise for the treatment of a variety of hematopoietic abnormalities. Therapy with r-HuEPO can raise the hematocrit levels of patients with end-stage renal disease. Therapy with GM-CSF in patients undergoing marrow transplantation results in acceleration of granulocyte and platelet recovery by 1 to 2 weeks, leading to fewer infections and earlier discharge from the hospital. Other demonstrated uses of GM-CSF include treatment for aplastic anemia, myelodysplastic syndromes, chemotherapy-induced neutropenia, and neutropenia associated with the acquired immunodeficiency syndrome (AIDS). Similar beneficial effects have been reported with G-CSF. Other hematopoietic growth factors, including the interleukins (IL)-1, -3, and -6, will soon be entering clinical trials. For the first time, the availability of a large number of hematopoietic growth factors may allow physicians to regulate closely the entire hematopoietic system of their patients.
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PMID:The clinical use of hematopoietic growth factors. 247 5


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