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)

Monosomy 7 occurs in approximately 5% of cases of myelodysplastic syndrome (MDS) in children and is associated with a poor prognosis. The unbalanced translocation t(1;7) is common in therapy-related MDS in adults but is extremely rare in children, with only three cases reported to date. We describe a pediatric case of MDS with the unusual combination of monosomy 7 and unbalanced t(1;7) in two distinct clones. Both clones were detected at diagnosis and have persisted throughout the course of MDS in this patient, a 16-year-old boy without prior exposure to known mutagens. Because of recurrent severe infections associated with neutropenia, he was treated with recombinant human granulocyte-macrophage colony-stimulating factor. This therapy improved the neutrophil count but did not alter the karyotype or the progression of disease.
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PMID:Monosomy 7 and unbalanced t(1;7) in an adolescent boy with myelodysplastic syndrome. 162 98

High-dose methylprednisolone therapy (HDMP) induces acceleration of leukocyte recovery in acute lymphoblastic leukemia (ALL) and the differentiation of myeloblasts to mature granulocytes in acute myeloblastic leukemia (AML). These effects of corticosteroids have been shown to be due to the enhanced colony-stimulating activity (CSA) and responses to corticosteroids in some patients with aplastic anemia and myelodysplastic syndromes (MDS) have been related to increased CSA activity. We measured the serum (granulocyte-macrophage colony-stimulating factor (GM-CSF) levels by a sandwich linked immunoabsorbent assay (ELISA) in patients with ALL and AML at presentation and following high-dose methylprednisolone (HDMP) therapy. Serum GM-CSF levels at presentation in the ten cases studied ranged between 160 and 700 pg/ml (mean 418.5 +/- 252.5). One week following HDMP therapy GM-CSF levels increased to between 260 and 950 pg/ml (733.5 +/- 203.2). Four weeks after therapy the GM-CSF levels increased to between 470 and 1350 pg/ml (911 +/- 278.7). GM-CSF levels were markedly elevated one week after HDMP in the patients with ALL, suggesting that in addition to the lymphotoxic effects on leukemic blasts, the acceleration in neutrophil recovery may be due to release of GM-CSF induced by HDMP and its effects on myeloid progenitors.
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PMID:The effect of high-dose methylprednisolone treatment on GM-CSF level in children with acute leukemia: a pilot study. 163 79

Mast cell growth factor (MGF), the ligand for the c-kit receptor, has been shown to be a hematopoietic growth factor that preferentially stimulates the proliferation of immature hematopoietic progenitor cells (HPC). We studied the effect of MGF on the in vitro growth of clonogenic leukemic precursor cells in the presence or absence of interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), and/or erythropoietin (EPO). Leukemic blood and bone marrow cells from patients with various types of acute myeloid leukemia (AML), chronic myeloid leukemia (CML) in chronic phase, as well as bone marrow samples from patients with myelodysplastic syndromes (MDS) were studied. MGF as a single factor did not induce significant colony formation by clonogenic leukemic precursor cells. In the presence of IL-3 and/or GM-CSF, MGF weakly stimulated the colony formation by clonogenic precursor cells from patients with AML. In contrast, in the presence of IL-3 and/or GM-CSF, MGF strongly induced both size and number of leukemic colonies from patients with CML in chronic phase. Furthermore, in the presence of EPO, MGF strongly stimulated erythroid colony formation by CML precursor cells. Cytogenetic analysis of the colonies showed that all metaphases after 1 week of culture were derived from the leukemic clone. In patients with MDS, MGF strongly stimulated myeloid colony formation in the presence of IL-3 and/or GM-CSF (up to fourfold), and erythroid colony formation in the presence of EPO (up to eightfold). Not only the number, but also the size of the colonies increased. In the presence of MGF, the percentage of normal metaphases increased in three patients tested after 1 week of culture compared with the initial suspension, suggesting that the normal HPC were preferentially stimulated compared with the preleukemic precursor cells. In the absence of exogenous EPO and in the presence of 10% human AB serum, MGF in the presence of IL-3 and/or GM-CSF induced erythroid colony formation from normal bone marrow and patients with MDS or CML, illustrating that MGF greatly diminished the EPO requirement for erythroid differentiation. These results indicate that MGF may be a candidate as a hematopoietic growth factor to stimulate normal hematopoiesis in patients with acute myeloid leukemia, or with myelodysplastic syndromes.
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PMID:Effect of mast cell growth factor (c-kit ligand) on clonogenic leukemic precursor cells. 163 26

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.
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PMID:Cytogenetic effects on cells derived from patients with myelodysplastic syndromes during treatment with hemopoietic growth factors. 164 Jul 27

Restriction fragment length polymorphisms (RFLP) of the X-chromosome genes phosphoglycerate kinase and hypoxanthine phosphoribosyl transferase were used in conjunction with cytogenetic analysis to study the clonality of hematopoiesis in four female patients with myelodysplastic syndromes, treated with either granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-3 (IL-3), and in one patient with essential thrombocythemia (ET) treated with IL-3. Both conventional karyotyping and X-inactivation analysis demonstrated the persistence of a monoclonal pattern of hematopoiesis in the two patients with refractory anemia (RA) treated either with GM-CSF or with IL-3. The partial restoration of non-clonal hematopoiesis was observed in one patient with RA and an excess of blasts following treatment with a combination of GM-CSF and low dose cytosine arabinoside. In a fourth patient with RA and in the patient with ET, treatment with IL-3 resulted in the complete restoration of a non-clonal pattern of peripheral blood cells. In contrast, the bone marrow cells remained monoclonal by Southern blot analysis in the patient with RA in whom it could be tested. Non-clonal lymphocytes appear to have been released into the peripheral blood in the two latter cases and are responsible for the non-clonal RFLP pattern. These results suggest that cytokine therapy may have diverse effects on hematopoiesis, including the release of residual normal cells into the peripheral blood.
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PMID:In vivo effects of granulocyte-macrophage colony-stimulating factor and interleukin-3 on clonal and non-clonal cell populations in patients with clonal hematopoietic disorders. 167 79

In order to obtain more insight into the nature of the abnormal in vitro colony formation in myelodysplastic syndromes (MDS), we investigated the kinetics of the colony formation of 23 MDS cases in response to recombinant human interleukin-3 (IL-3), Granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating Factor (G-CSF), and giant cell tumor cell line conditioned medium (GCT-CM). The kinetics of GCT-CM-induced colony formation were comparable to that of G-CSF-induced colony growth, both in MDS and in normal bone marrow cultures. Colony formation was found to be delayed in MDS. The delay in colony formation was most apparent in the GCT-CM (G-CSF) responsive progenitor cell compartment. In MDS cases with clinical features of high risk disease, this delay was more pronounced as compared with low risk cases (7 and 3 days, respectively, in response to GCT-CM). The delay in colony formation was found to be caused by an increase in the time interval before progenitor cells had begun to divide. These results suggest that a prolongation of the time spent in G0 of myeloid progenitor cells in MDS may be the cause of the indolent in vitro colony formation observed in this disease.
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PMID:The effects of interleukin-3, GM-CSF, and G-CSF on the growth kinetics of colony-forming cells in myelodysplastic syndromes. 169 40

Chromosomes of bone marrow cells obtained from nine patients with myelodysplastic syndrome (MDS) were assessed after in vitro co-culture (48 hours culture) with recombinant human granulocyte colony-stimulating factor (rhG-CSF), recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF), or recombinant human erythropoietin. Three of the nine MDS cases showed no cytogenetic abnormalities with or without any recombinant human hematopoietic growth factors; one MDS patient with a t(3;4) did not show any change in the proportion of cells with this cytogenetic change. The remaining five cases exhibited changes in the frequency of subclones after the treatment. An increasing number of metaphase cells with less complex chromosome abnormalities was observed in two of the five cases by treatment with rhG-CSF; one of them also showed an increasing number of cells with normal karyotypes. After rhGM-CSF treatment, cells with nonclonal hyperdiploid abnormalities appeared in one MDS patient. After erythropoietin treatment, an increasing number of cells with a prototypic change was observed in one MDS patient, whereas one patient showed an increasing number of cells with an additional chromosome abnormality. These observations indicate that hematopoietic growth factors possibly modify the constitution of marrow cells with multiple chromosome abnormalities and the degree is different in each MDS patient. Furthermore, a chromosome analysis using an in vitro culture system with human recombinant hematopoietic growth factors may be able to detect metaphase cells with additional chromosome abnormalities in some MDS patients.
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PMID:In vitro cytogenetic effects of recombinant human hematopoietic growth factors on cells derived from myelodysplastic syndromes. 169 82

The regulation of haemopoiesis in myelodysplastic syndromes (MDS) was evaluated by measuring and comparing the in vitro response of marrow progenitors from 18 MDS patients to stimulation with recombinant haemopoietic growth factors (HGFs), granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte CSF (G-CSF) and interleukin-3 (IL-3). A similar pattern of colony growth was detected with all three HGFs in most MDS patients, exhibiting subnormal growth of GM-CFU and markedly poor to absent growth of BFU-E and CFU-GEMM. A common severe impairment in the growth of all colony types with all three HGFs was observed in five patients, four of whom presented with pancytopenia. The stimulation of MDS marrow progenitors with a five-fold higher than control saturating dose of HGFs induced a significant increase in the frequency of one, two, or all three colony types in cultures of 14 patients, whereas colony numbers in control (n = 8) marrow cell cultures were not significantly changed. All four of the non-responders were pancytopenic and three exhibited markedly impaired colony growth. Supersaturating GM-CSF, G-CSF and IL-3 increased GM-CFU numbers in six, three, and three patients, respectively. The values for BFU-E were three, six, and seven and for CFU-GEMM two, one, and five. The enhancement of MDS marrow colony numbers by supersaturating HGFs which exert their effects directly or via the action of marrow accessory cells, suggests that the progenitor cell growth abnormalities in these disorders may involve a defect in the capacity of accessory and/or progenitor cells to respond to stimulation with specific haemopoietic growth regulators.
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PMID:Impaired response of myelodysplastic marrow progenitors to stimulation with recombinant haemopoietic growth factors. 170 45

The myelodysplastic syndromes are clonal hematopoietic stem cell disorders characterized by varying degrees of pancytopenia and often a progression to acute myeloid leukemia. Recent evidence has linked myelodysplastic syndromes to environmental and occupational genotoxic exposure. Specific cytogenetic abnormalities are well described in myelodysplastic syndromes and have been demonstrated to be useful diagnostic and prognostic tools. Activation of protooncogenes such as ras and fms have also been noted in myelodysplastic syndromes; however, their contribution to the pathogenesis of the syndrome remains to be determined. Aggressive leukemia-like induction therapy, differentiating agents (low-dose cytarabine, 13-cis-retinoic acid) have had little impact on overall survival in myelodysplastic syndromes. The recombinant hematopoietic growth factors (granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor) may be of significant benefit to patients with myelodysplastic syndromes, although it remains to be determined whether they will have a substantial impact on survival. Allogeneic bone marrow transplantation is the only potentially curable treatment of myelodysplastic syndromes. The advanced age of these patients as well as the lack of histocompatible donors restricts this modality to only a small proportion of patients.
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PMID:Recent advances in biology and treatment of myelodysplasia. 171 May 5

We investigated the effects of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) and recombinant human granulocyte colony-stimulating factor (rhG-CSF) therapy on the natural killer (NK) cell lineage in patients with aplastic anemia and myelodysplastic syndrome. Selected bone marrow (BM) cells were prepared by the elimination of nylon wool-adherent cells and mature T and NK cells from BM cells. The frequency of BM NK progenitors relative to BM cells selected was significantly decreased 4 weeks after the start of rhGM-CSF therapy (P less than .01), while the peripheral blood NK cell count and NK activity were also significantly decreased (P less than .05). A return to the pretreatment levels was seen 4 weeks after the cessation of treatment in all cases. No suppressive effect was noted in the patients who received rhG-CSF therapy. These results suggest that rhGM-CSF therapy suppresses the generation of NK cells from human BM NK progenitors.
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PMID:Inhibitory effect of granulocyte-macrophage colony-stimulating factor therapy on the generation of natural killer cells. 172 Jul


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