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

This paper reports on a patients with congenital Pelger-Huet anomaly who developed myelodysplastic syndrome (MDS). A 45-year-old female was referred for investigation of pancytopenia of 6 months' duration. Hereditary Pelger-Huet anomaly was diagnosed by family study 7 years prior to admission. On admission, Hb was 6.5 g/dl, Ht 19.9%, Platelets 1.8 x 10(4)/microliters, and WBC 1,200/microliters with 2% myelocytes, 9% metamyelocytes, 14% bands, 2% segmented neutrophils, 58% lymphocytes and 5% monocytes. Most of the granulocytes were Pelger-Huet type with strikingly clumped nuclear chromatin. Bone marrow aspirate demonstrated 3.6% blasts and dysplastic changes including megaloblastoid features in erythroid series and micro-megakaryocytes compatible with refractory anemia, a subtype of MDS. The association of hereditary Pelger-Huet anomaly and MDS is discussed.
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PMID:[Myelodysplastic syndrome in a patient with familial Pelger-Huet anomaly]. 175 52

A 62-year-old woman was admitted to our hospital because of general malaise in May, 1987. No hepatosplenomegary, skin eruption or lymphadenopathy was detected. Laboratory examinations showed mild anemia, thrombocytopenia, normal leukocyte count with no lymphocyte abnormality, hypogranular neutrophils, elevated serum lactic dehydrogenase, increased C-reactive protein and hypoxia. Bone marrow aspirate was normocellular with dysplastic changes in erythroid and megakaryocytic lines which agree with a diagnosis of myelodysplastic syndrome (MDS). She was treated with prednisolone which relieved her symptom but she developed high fever, hemiplegia and disturbance of consciousness and died in August, 1987. Necropsy of the kidney revealed large mononuclear cells within the lumen of small blood vessels. Immunohistochemical study of these malignant cells showed positive reaction to the anti-LCA and anti-L26 antibodies. And electron microscopy showed no azure granules in these cells. Then we diagnosed as neoplastic angioendotheliosis (NAE). To our knowledge, this is the first report of NAE with abnormalities in myeloid, erythroid and megakaryocytic lineages. These results suggest that NAE with MDS originate from a multipotent stem cell.
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PMID:[Myelodysplastic syndrome with neoplastic angioendotheliosis: report of a case]. 175 62

Hemoglobin (Hb) synthesis in colony-forming-unit erythroid (CFU-E) colonies from the bone marrow of 10 normal subjects and 6 patients with myelodysplastic syndromes (MDS) was studied using microcytofluorometry. Hb content was determined utilizing a photochemical reaction in which the intracellular Hb is converted into fluorescent porphyrin. Briefly, the CFU-E in plasma clots was assayed according to Tepperman's method. Bone-marrow mononuclear cells were then dispensed onto petri dishes containing the plasma clots. The cells in plasma clots were cultured for seven days and then air-dried. The samples were then fixed with pure methanol. Thereafter, the dishes were exposed to ultraviolet light (lambda = 405 nm) in the presence of an SH-donor (0.2 M mercaptoethylamine hydrochloride). The intensity of porphyrin fluorescence was measured using a microcytofluorometer. When the photochemical reaction was carried out for 50 min, the intensity of fluorescence was found to be proportional to the mean corpuscular Hb (MCH) level, suggesting that the intracellular Hb level can be determined as a function of the intensity of this fluorescence. The number of CFU-E colonies in MDS patients was smaller than that in normal subjects. In addition, intracolony Hb level was markedly lower in the MDS cases than in normal subjects. Our findings suggest that the maturation process of CFU-E is impaired in MDS patients.
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PMID:[Qualitative and quantitative evaluation of CFU-E colonies in myelodysplastic syndromes]. 177 72

Erythropoietin is a glycoprotein hormone that plays a vital role in erythropoiesis. It is mainly produced in the fetal liver till the third trimester of pregnancy. At that point, the kidney interstitium takes over this function and becomes the main source of erythropoietin. Hypoxia stimulates erythropoietin production by a mechanism that may require a heme protein as a second messenger. Erythropoietin stimulates the maturation of erythroid precursors (colony-forming unit-erythroid and burst-forming unit-erythroid) via at least two types of cell surface receptors. The higher-affinity receptors appear to be more important in modulating the effects of erythropoietin in vivo. Changes in intracellular calcium may ultimately mediate the action of erythropoietin on erythroid precursors. A specific and sensitive radioimmunoassay is now available for accurately measuring erythropoietin levels. All forms of erythrocytosis except polycythemia vera are associated with elevated erythropoietin levels. Levels are also high in cord blood obtained following fetal asphyxia. Reduced levels are seen in patients with anemia due to renal diseases. The response of erythropoietin to the degree of anemia appears to be attenuated in patients with cancer, chronic diseases, and human immunodeficiency virus (HIV) infection. Erythropoietin has been successfully used for treating patients with anemia due to renal failure. Its use has also been approved for the treatment of anemia patients receiving zidovudine for HIV infection. Encouraging results have been observed when erythropoietin was used to treat anemia due to rheumatoid arthritis, hematological malignancies, and prematurity. It has also been used to increase the yield of autologous blood collected prior to an elective surgical procedure. However, it has not proved to be useful in sickle cell anemia and myelodysplastic syndromes.
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PMID:Erythropoietin. Biology and clinical applications. 178 66

We have established a new nonlymphoid leukemic cell ine from a patient with myelodysplastic syndrome (MDS), which progressed to overt leukemia. The parental cell line and a subline derived from this line have absolute dependency on several cytokines for their long-term survival and growth. The parental line designated F-36P requires granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-3 (IL-3) for continuous growth, while a subline designated F-36E can be maintained in the presence of erythropoietin (Epo) alone. When these cytokines are depleted, both the parental and the subline cells die within several days, even in medium supplemented with fetal calf serum (FCS). F-36E, maintained in the presence of Epo, constitutively synthesizes hemoglobin at a significant level. F-36P, which is usually maintained in the presence of GM-CSF or IL-3, can be induced to synthesize hemoglobin when GM-CSF or IL-3 is substituted by Epo. The surface marker profile shows that the F-36P cells are positive for the leukocyte common antigen (CD45) and some common multilineage markers such as CD13, CD33, and CD34, and negative for T- and B-cell antigens and mature myelomonocytic antigens. However, some monoclonal antibodies recognizing erythroid and platelet glycoproteins react with these cells. Thus, this cell line has a multilineage phenotype, suggesting that the transformation event occurred in a multipotent stem cell. It is also evident that the F-36 cells can be induced to differentiate into the erythroid lineage in the presence of Epo. This, to our knowledge, is the first description of a human leukemic cell line that can be stimulated to synthesize hemoglobin by Epo.
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PMID:Establishment and erythroid differentiation of a cytokine-dependent human leukemic cell line F-36: a parental line requiring granulocyte-macrophage colony-stimulating factor or interleukin-3, and a subline requiring erythropoietin. 183 51

Quantitative and qualitative evaluations of erythrocyte ferritin in 161 patients with RA and RAEB in MDS, AML, CML, PV, PA, HS, IDA, chronic liver disease and alcoholic liver disease were carried out. Mean erythrocyte ferritin levels of patients with RA, AML, PA, HS and alcoholic liver disease were increased compared with normal subjects. On isoelectric focusing analyses (IEF), erythrocyte ferritin in normal subjects were detected between pI 5.1 and 5.7. In the cases of RA, pI ranges of erythrocyte ferritin may be divided into three groups, acidic, neutral, basic shift on IEF respectively. In these groups, the more acidic the ferritin shift, the higher the proportion of morphological abnormalities of the erythroid precursors in the bone marrow was observed. In patients with AML (M2, M3, M4), little difference was found among these three subtypes, and all of the cases showed similar pattern with normal subjects on IEF. The ferritin from IDA showed low levels and slight basic shift compared with normal subjects on IEF, and these features were also found in patients with CML (chronic phase) and PV. After iron supplementation, marked increase of acidic ferritin was detected on IEF indicating an intermediate store for iron destined for haem synthesis. It was clear that the stainable iron in liver parenchymal cells were found at erythrocyte ferritin concentration 20 ag/cell or over in patients with chronic liver disease. Measurement of erythrocyte ferritin concentration is a helpful method for evaluating iron deposition in hepatocyte non-invasively. From these results it is considered that quantitative and qualitative analyses of erythrocyte ferritin are very useful for evaluating erythropoiesis as well as iron metabolism.
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PMID:[Clinical significance of erythrocyte ferritin]. 189 Jul 34

In a phase II study, 12 patients with a myelodysplastic syndrome (MDS) and anaemia (nine transfusion-dependent) were treated with recombinant human erythropoietin (rHuEpo) to assess the therapeutic effect on erythropoiesis and on transfusion requirement. Patients with a low risk of developing acute leukaemia were included, i.e. refractory anaemia (RA), RA with ringed sideroblasts (RARS) and RA with excess blasts (RAEB), providing the percentage of myeloblasts in the bone marrow did not exceed 10%. Recombinant HuEpo treatment was initiated at a dose of 50 units/kg body weight and administered subcutaneously three times weekly. At 3-week intervals the dose was increased with 50 units/kg per injection, until after 15 weeks a maximum dose of 250 units/kg three times weekly was reached. All patients completed the study. Recombinant HuEpo was well tolerated and no serious side effects were seen. There was no evidence of the emergence of a new malignant clone in response to rHuEpo as shown by sequential karyotyping. In none of the patients was an increase in haemoglobin level or a diminished red blood cell transfusion requirement seen. In four out of 10 evaluable sequential bone marrow smears, an increase in erythropoiesis was seen, suggesting stimulation of ineffective red cell production. One of these patients also showed a rise in reticulocyte count. The number of erythroid progenitor cells (BFU-E and CFU-E) in blood and bone marrow was not affected by rHuEpo treatment. Also no change in the number of myeloid progenitor cells (CFU-GM) in blood and bone marrow was noted. In conclusion, subcutaneous treatment with rHuEpo at dosages up to 250 units/kg body weight (three times weekly) fails to increase the haemoglobin level or to diminish the transfusion requirement in patients with MDS and anaemia. It is unclear whether higher doses of rHuEpo are effective or whether patients with less severe anaemia who are transfusion independent, have a higher likelihood of response.
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PMID:Effect of subcutaneously administered human recombinant erythropoietin on erythropoiesis in patients with myelodysplasia. 191 40

In 1987, a 50-year-old patient presented with isolated thrombocytopenia (27,000/mm3) which proved to be refractory to steroid medication and high i.v. doses of immunoglobulin. Two years later he developed macrocytic anemia. Chromosomal analysis confirmed the diagnosis of myelodysplastic syndrome (MDS), refractory anemia type with blast excess. Cytogenetically, three cellular populations were observed: one normal (75% of metaphases) and two abnormal, clone A (2%) 46,XY, del(5q), del(11q), and clone B (23%) 46,XY, del(5q), del(11q) plus 2 other anomalies. Evolution was characterized by worsening of the bicytopenia with marked hypoplasia of the megakaryocytic and erythroid series while the percentage of blasts remained stable. Concerning the chromosomal markers, the normal population disappeared and clone A became predominant (clone A 97%, clone B 3%). This case shows that isolated thrombocytopenia can be the sole initial manifestation of MDS. We discuss the possibility that "refractory thrombocytopenia" constitutes a diagnostic category like refractory anemia or refractory anemia with ring sideroblasts. The proliferative advantage of clone A or the disadvantage of clone B may be due to the occurrence of new, cytogenetically non-detectable mutations.
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PMID:[Unusual initial manifestation in a case of refractory anemia with excess of blasts]. 194 47

Cytogenetic and bone marrow culture studies were performed sequentially in 13 patients with myelodysplastic syndromes (MDS) who responded to low dose cytosine arabinoside (Ara-C) treatment (complete in nine and partial in four patients). Of nine patients with initial clonal karyotypic abnormalities, six recovered a normal karyotype after attaining a response to treatment, but the other three patients retained partial or total karyotypic abnormalities. A new clonal karyotypic abnormality appeared after treatment in one patient. Eight patients showed normal colony growth of both granulocyte-macrophage colony-forming units and erythroid burst-forming units after treatment, but five were still defective. There was a clear difference in the duration of response to treatment between these two groups. Consolidation treatment was not effective in patients with persistent karyotypic abnormalities or defective colony formation. Although the number of patients studied is small, these results suggest that hemopoiesis in patients with MDS following a response to treatment with low dose Ara-C is heterogeneous. Consolidation chemotherapy is recommended to ensure and prolong the response in patients showing normalization of both cytogenetic and bone marrow culture results.
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PMID:Cytogenetic and clonal culture evaluation after response to low dose Ara-C in myelodysplastic syndromes. 196 Oct 37

Hematological disorders are commonly complicated by anemia, and the symptoms of red cell deficiency adversely affect the quality of life. Erythropoietin is a glycoprotein which controls red blood cell production. Recombinant human erythropoietin, 50 U/kg/day, was given subcutaneously to 16 patients with myelodysplastic syndrome and anemia. All but one patient was transfusion dependent. Diverse pretreatment endogenous serum erythropoietin levels were noted and ranged from 17 to 3616 IU/l. Two patients (12.5%) demonstrated an improvement in hemoglobin levels obviating the need for transfusions. Their responses lasted 5+ and 7 months with maintenance erythropoietin treatment. The responders had endogenous serum erythropoietin levels of 44 and 170, respectively. Treatment was generally tolerated without constitutional side-effects. However, three patients developed thrombocytopenia and one developed joint pain and leukocytosis on treatment. Overall, six patients showed changes in non-erythroid cells: two patients had an increase in platelet counts; three patients, a decrease in platelet counts; and one patient, an increase in white blood cell counts. Most of these changes reversed rapidly once erythropoietin was stopped. It is concluded that (a) serum erythropoietin levels are extremely variable in anemia patients with myelodysplastic syndrome, (b) only a minority of patients benefit from treatment with recombinant human erythropoietin, and (c) erythropoietin can affect cells of the myeloid and megakaryocytic lineage in a small proportion of patients.
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PMID:Erythropoietin treatment in patients with myelodysplastic syndrome and anemia. 196 Oct 41


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