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Query: UMLS:C0026986 (myelodysplastic syndrome)
 14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The erythrocyte enzyme activities in twenty-six cases of myelodysplastic syndromes were determined. There were remarkably abnormal levels in seven cases; namely, four cases showed increased hexokinase activity, three cases showed increased pyruvate kinase activity, and two cases showed increased adenosine deaminase activity. Among these, one case with elevated pyruvate kinase activity showed the novel expression of M2-type pyruvate kinase activity, in addition to the R-type pyruvate kinase activity normally found in erythrocytes. Southern blotting of peripheral leucocyte DNA revealed only an amplified PK-LR genome, which derived from the chromosomal abnormality of a 1;7 translocation. The mechanism responsible for switching M2-type to R-type during erythroid maturation was considered to be partially disrupted in this case.
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PMID:Erythrocyte enzyme activities in myelodysplastic syndromes: elevated pyruvate kinase activity. 291 62

It has been shown that haem arginate treatment increases blood cell counts, improves the sideroblast status of the bone marrow and normalises decreased activities of haem synthesising enzymes in some patients with acquired sideroblastic anaemia, or with other types of myelodysplastic syndromes. 4 patients with hereditary sideroblastic anaemia (HSA), belonging to two families, were therefore treated with haem arginate infusions, 3 mg/kg, on 4 consecutive days, and thereafter weekly for 10 wk. No effect was observed on the mildly anaemic haemoglobin levels or on the red cell counts. However, the initially low or low-normal myeloid to erythroid ratio in the marrow increased in all patients. A consistent decrease in the percentage of ring sideroblasts and other abnormal sideroblasts was seen in 1 patient (Family A), and a temporary decrease of abnormal sideroblasts took place during the most intensive treatment period in 2 other patients (Family B). Two of three initially abnormal haem synthesising enzyme activities became normal in Family A, whereas no clearly consistent effects on the haem synthesising enzymes were observed in Family B. The present study shows that haem arginate infusions can normalise the activities of haem synthesising enzymes in some patients with HSA. Further studies are needed to evaluate the impact of haem infusions on the iron balance of these patients.
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PMID:Haem arginate treatment for hereditary sideroblastic anaemia. 291 95

Six patients had primary sideroblastic erythropoiesis together with a haemoglobin concentration of 12.0 g/dl or higher. In four cases this was associated with macrocytosis. Other abnormalities included failure of erythroid progenitor growth from peripheral blood in three cases and occasional dysplastic appearances in neutrophils and megakaryocytes. Sideroblastic erythropoiesis seems to be an early manifestation of the myelodysplastic syndrome and may present clinically at a pre-anaemic stage.
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PMID:Primary acquired sideroblastic erythropoiesis in non-anaemic and minimally anaemic subjects. 292 46

The myelodysplastic syndromes represent a preleukaemic state in which a clonal abnormality of haemopoietic stem cell is characterised by a variety of phenotypic manifestations with varying degrees of ineffective haemopoiesis. This state probably develops as a sequence of events in which the earliest stages may be difficult to detect by conventional pathological techniques. The process is characterised by genetic changes leading to abnormal control of cell proliferation and differentiation. Expansion of an abnormal clone may be related to independence from normal growth factors, insensitivity to normal inhibitory factors, suppression of normal clonal growth, or changes in the immunological or nutritional condition of the host. The haematological picture is of peripheral blood cytopenias: a cellular bone marrow, and functional abnormalities of erythroid, myeloid, and megakaryocytic cells. In most cases marrow cells have an abnormal DNA content, often with disturbances of the cell cycle: an abnormal karyotype is common in premalignant clones. Growth abnormalities of erythroid or granulocyte-macrophage progenitors are common in marrow cultures, and lineage specific surface membrane markers indicate aberrations of differentiation. Progression of the disorder may occur through clonal expansion or through clonal evolution with a greater degree of malignancy. Current attempts to influence abnormal growth and differentiation have had only limited success. Clinical recognition of the syndrome depends on an acute awareness of the signs combined with the identification of clonal and functional abnormalities.
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PMID:Myelodysplastic syndromes: pathogenesis, functional abnormalities, and clinical implications. 299 94

Male Wistar rats received repeated pulse doses of 7,12-dimethylbenz(a)anthracene (DMBA), known to elicit myelodysplasia followed by acute, mostly erythroblastic, leukemia at 10-day intervals. The recovery of spleen colony forming hemopoietic stem cells (CFU-s) surviving the cytocidal action of DMBA was examined between pulses. Recovery after a pulse of 35 mg/kg body weight varied with the organ source of the CFU-s (femoral bone marrow or spleen) and the number of preceding DMBA pulses. After a single DMBA pulse bone marrow CFU-s initially recovered faster than reported for normal bone marrow CFU-s transplanted into chemically conditioned rats. But recovery was followed by regeneration arrest. Population doubling times of marrow CFU-s increased with the number of DMBA pulses. Recovery of splenic CFU-s was slower after a single DMBA pulse than reported for normal spleen CFU-s transplanted into chemically conditioned rats. The CFU-s population doubling times were not significantly different after a single or five DMBA pulses. After three pulses, however, recovery of splenic CFU-s was exceedingly slow until day 5 and subsequently accelerated, but was still slower than after one or five pulses. In the spleen CFU-s recovery was always accompanied by regeneration of total cell numbers with a preference for erythroid regeneration. In the bone marrow this was the case after three DMBA pulses only.
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PMID:Recovery patterns of rat hemopoietic stem cells between pulse doses of 7,12-dimethylbenz(a)anthracene (DMBA) applied in a leukemogenic regimen. 309 51

Erythropoietic activity in patients with myelodysplastic syndrome (MDS) was evaluated by ferrokinetic measurements. Since the conventional plasma iron turnover of MDS patients increased with plasma iron levels after multiple blood transfusions, erythron transferrin uptake was chosen as a parameter of erythroid marrow activity. Although a correlation was shown between plasma iron level and plasma iron turnover (r = 0.50, 0.01 less than p less than 0.02), no correlation existed between the plasma iron level and erythron transferrin uptake (r = 0.25, p greater than 0.1). Erythron transferrin uptake, independent of plasma iron, was significantly higher in MDS patients than in normal subjects (110.6 +/- 67.6 and 67.6 +/- 18.8 mumol/l/dl, respectively; 0.01 less than p less than 0.02). An increased erythropoiesis occurring concomitantly with morphologically normal or increased erythroid cellularity was demonstrated in patients with MDS. The measurement of erythron transferrin uptake might be valuable as an accurate expression of erythroid activity in the hyperferremic state.
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PMID:Ferrokinetic evaluation of erythropoiesis in patients with myelodysplastic syndromes. 312 77

Cytogenetic studies as well as erythroid and myeloid progenitor cell assays were performed in a 29-yr-old epileptic man with pure red cell aplasia (PRCA) who had been treated with primidone for several years. Despite clinical evidence of preleukemia, our studies indicated an underlying atypical Philadelphia chromosome-positive myeloproliferative disorder. These laboratory findings were confirmed by the subsequent development of chronic myeloid leukemia (CML) which terminated in a CALLA-positive lymphoblastic crisis 32 months later. The rare concurrent occurrence of PRCA and CML and the possible inducing role of the preceding antiepileptic treatment are discussed.
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PMID:Pure red cell aplasia as possible early manifestation of chronic myeloid leukemia. 312 3

Dihydrofolate reductase (FH2-R) was studied cytochemically in the bone marrow erythroblasts of 20 normal controls and 46 patients with myelodysplastic syndromes (MDSs) classified according to FAB, prior to therapy. The reaction product was quantified for the same samples with a Vickers M86 microdensitometer. The enzyme activity progressively decreased during the normal differentiation of the erythroid cells and persisted at high levels in MDS cells. The high level of FH2-R may be related to the malignant transformation of the cells, or to increased compensatory erythropoietic activity of ineffective erythropoiesis, or to both.
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PMID:Qualitative and quantitative study of dihydrofolate reductase in myelodysplastic syndromes. 313

The clinical, hematologic, and phenotypic features of 28 patients with acute leukemia with megakaryocytic involvement (AMKL) were analyzed. The prevalence of this type of leukemia in the entire series was 11.6%, with a higher incidence among patients with acute transformation of a previous myeloproliferative disorder (MPD) (24%) than among the transformed myelodysplastic syndrome (13%) patients. The incidence in the "de novo" ANLL was 8% and 16% among secondary leukemias. The presence of bone marrow fibrosis together with low WBC and normal or increased platelet counts despite a severe anemia are the most relevant features in these patients who otherwise displayed an apparently poor prognosis. Megakaryoblasts were morphologically recognized more frequently in the acute transformations of MPD than in de novo ANLL. Only two cases were considered pure AMKL, and in the remaining 26 patients, megakaryoblasts coexisted with other granulomonocytic and/or erythroid populations. Antiglycoprotein IIIa (anti-GPIIIa) (C17) and anti-GPIIb/IIIa (CDw41-, J15-) antibodies are probably the best markers for AMKL, although the monoclonal antibody against GPIX (FMC25) was also positive in a majority of cases but in a lower percentage of cells. On the other hand, megakaryoblasts were generally negative for granulocytic or monocytic markers (CD13, CD14, CD15); the expression of HLA-DR antigens in these cells was variable. Our present results indicate that megakaryoblastic involvement is more common than previously recognized. This is true not only in acute transformed leukemias but also in de novo ANLL. Although the diagnosis of these cases should be based on megakaryocytic markers, it is often possible to suspect a diagnosis according to certain clinical and hematologic features.
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PMID:Leukemias with megakaryoblastic involvement: clinical, hematologic, and immunologic characteristics. 316 92

Bone marrow cells from patients with leukemia, myelodysplastic syndromes, cancer, and other disorders on a phase I clinical trial with recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) were assessed in vitro for numbers of granulocyte-macrophage (CFU-GM), erythroid (BFU-E), and multipotential (CFU-GEMM) progenitor cells, and for growth patterns (colony-to-cluster ratio) of CFU-GM, cycling rates of CFU-GM, and responsiveness in vitro to colony-stimulating and colony-inhibiting factors. The colony-to-cluster ratio of CFU-GM and the dose-response curves of CFU-GM to stimulation by rhGM-CSF in vitro did not change during the clinical trial. However, the percentage of CFU-GM in DNA synthesis, which is a measure of the proliferative rates of these cells, determined by the high specific activity tritiated thymidine kill technique in vitro, was markedly enhanced in a reversible fashion after administration in vivo of rhGM-CSF. The increased cycling rates of CFU-GM were consistent with the induced increase in neutrophil counts in these patients that has been reported elsewhere. Additionally, marrow CFU-GM from patients given rhGM-CSF in vivo were increased in sensitivity to inhibition in vitro by recombinant human H-subunit (acidic) ferritin in two of eight cases, and were increased in sensitivity to inhibition by lower dosages of recombinant human tumor necrosis factor alpha in all patients evaluated. The sensitivity of CFU-GM to inhibition in vitro by recombinant human interferon gamma and prostaglandin E1 did not change during the clinical trial. These studies demonstrate that the rhGM-CSF is having an effect on CFU-GM in the patients on the phase I clinical trial. This information may be of significance in planning future clinical studies combining rhGM-CSF with chemotherapy and/or other biotherapy.
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PMID:Growth characteristics of marrow hematopoietic progenitor/precursor cells from patients on a phase I clinical trial with purified recombinant human granulocyte-macrophage colony-stimulating factor. 326 May 58


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