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

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

The clonal origin of granulocyte-macrophage colony forming cells (CFU-GM) in the myelodysplastic syndrome (MDS) was cytogenetically studied. Chromosome analysis was carried out on single GM-colonies from six patients with MDS, whose bone marrow cells had chromosome abnormalities. Abnormal clone-derived CFU-GM were grown in four patients under the presence of human placental conditioned medium. In the remaining two, all analysed colonies revealed a normal karyotype, although the majority of metaphase cells showed an abnormal karyotype in bone marrow preparations. These results indicate that the abnormal clone-derived CFU-GM in MDS have a clone-by-clone variation in colony forming ability in vitro.
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PMID:Heterogeneous colony forming ability in vitro of the abnormal clone-derived granulocyte-macrophage precursors in myelodysplastic syndromes. 318 86

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

Clinical responses of patients with acute leukemia (AL) following the myelodysplastic syndrome (MDS) to the standard therapy are poor. It is considered that the greatly decreased hemopoiesis in these cases is responsible for their clinical picture. We studied leukemia-associated inhibitory activity (LIA), which inhibited human granulocyte-macrophage progenitors, in these patients. Peripheral blood (PB) mononuclear cells (MNC) suppressive to granulocyte-macrophage colony formation were present in 3 of 5 cases of de novo AL and in 3 of 4 cases of AL following MDS. The PB MNC-cultured media from these cases also suppressed colony formation. The elution patterns of LIA of these cases were almost identical in gel chromatography. These results suggest that LIA may be responsible for the suppression of normal granulopoiesis in some patients with AL developed from MDS, and that the profound derangement of normal hemopoietic capability in these cases may be due to multiple complex factors.
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PMID:Leukemia-associated inhibitory activity in acute leukemia developed from myelodysplastic syndrome. 350 Oct 31

Megakaryocytic colony formation by precursor cells from the bone marrow was investigated in 10 patients with a myelodysplastic syndrome. All but one exhibited abnormal colony formation: four showed no colony formation at all, while a decreased number of colonies was noticed in five. All of the patients showed defective colony formation by erythroid progenitors, but only four showed clearly abnormal granulocyte-macrophage colony formation. The defect in megakaryocytic progenitors seems to be more akin to the defects occurring in erythroid progenitors than to the defects seen in the granulocyte-macrophage lineage.
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PMID:Megakaryocyte colony formation by bone marrow progenitors in myelodysplastic syndromes. 371 73

Peripheral blood (PB) granulocyte-macrophage progenitor (CFU-GM) growth was measured in 47 normal subjects and, together with bone marrow CFU-GM and blast cell numbers, in 45 newly diagnosed patients with myelodysplastic syndromes (MDS). Both PB colony and cluster numbers were significantly reduced in MDS patients. In patients with greater than 5% marrow blasts there was a negative correlation between blast cell numbers and PB colony growth. Bone marrow and PB colony growth were also well correlated in this group. Poor growth of PB CFU-GM appears to be more closely related to prognosis than does bone marrow progenitor growth.
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PMID:Peripheral blood granulocyte-macrophage progenitors in patients with the myelodysplastic syndromes. 378 Aug 88

Bone-marrow granulocyte-macrophage progenitor cell proliferation and regulatory factor (colony-stimulating activity; CSA) production were assessed at presentation and, if possible, subsequently in twenty-one patients with dysmyelopoiesis and less than 5% bone-marrow blasts. Seven patients underwent acute leukaemic transformation 1-35 months after the first marrow culture. Assay of bone-marrow endogenous CSA proved the most useful prognostic test. The rate of transformation in the seven patients with raised CSA at presentation was significantly greater (five transformed and one died at or before 4 months) than that in the fourteen patients with normal, low, or undetectable CSA (two transformed at 27 and 35 months). In one of the latter an increase in bone-marrow CSA occurred 6 weeks before transformation (serial marrow samples were not available in the other case). No other marrow culture feature measured, including the presence or absence of granulocyte-macrophage colony-forming cells and total clone numbers (colonies and smaller clusters) was as useful.
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PMID:Use of bone-marrow culture in prediction of acute leukaemic transformation in preleukaemia. 613 82

Marrow cytogenetic and granulocyte-macrophage colony formation (CFU-GM) studies were performed on 34 previously untreated patients with documented myelodysplastic syndromes seen between January 1978 and June 1982. All patients were managed without chemotherapy until progression to acute leukemia was observed. All 10 patients with exclusively abnormal marrow metaphases developed acute leukemia (100%) while only one (7%) of 14 patients with solely normal marrow metaphases subsequently developed leukemia (p less than 0.001). Three (42%) of the seven patients with both normal and abnormal marrow metaphases developed acute leukemia. Fifteen (86%) of the 19 patients with either large cluster or no growth patterns developed acute leukemia while only two (13%) of 15 patients with either small cluster or colony forming growth patterns developed acute leukemia (p less than 0.001). Abnormal marrow cytogenetic status correlated with abnormal marrow CFU-GM growth pattern (p less than 0.05). Analysis of CFU-GM sensitivity to inhibition by prostaglandin E was performed in 12 patients. Nine patients showed CFU-GM refractoriness to inhibition by prostaglandin E. Seven of these patients eventually developed leukemia. Three patients had CFU-GMs which were initially sensitive to prostaglandin E inhibition. In these three patients, a loss of CFU-GM sensitivity to prostaglandin E was observed prior to their progression to morphologically identifiable acute leukemia.
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PMID:Marrow cytogenetic and cell-culture analyses of the myelodysplastic syndromes: insights to pathophysiology and prognosis. 658 16

Colony formation by haematopoietic progenitors from the bone marrow was studied in 44 patients with a myelodysplastic syndrome. Erythroid progenitors BFU-E and CFU-E were cultured in methyl cellulose, and granulocyte-macrophage precursors CFU-GM in agar. 3 of 32 patients showed normal numbers of BFU-E colonies; in all the other cases the number of these colonies was below the normal range. CFU-E colony formation was subnormal in all cases. 23 of 44 patients grew normal numbers of colonies and clusters in CFU-GM cultures. These patients had refractory anaemia with ring sideroblasts (FAB-classification) or 5q-karyotype anomaly in the marrow. Patients lacking both of these findings exhibited reduced colony formation or excessive growth of colonies and/or clusters, with few exceptions. In conclusion, we found that erythroid colony formation was defective in all cases. Normal granulocyte-macrophage colony formation was associated with refractory anaemia with ring sideroblasts or the presence of 5q- karyotype anomaly.
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PMID:Erythroid and granulocyte-macrophage colony formation in myelodysplastic syndromes. 671 44

In vitro studies may serve as a guide to clinical strategies with cytokines. In this study, marrows from 26 patients with myelodysplastic syndrome (MDS) were assayed for myeloid progenitor cells in agar gel. Colony stimulating activity was provided by the recombinant human colony stimulating factors granulocyte-macrophage colony stimulating factor (GM-CSF), granulocyte colony stimulating factor (G-CSF), interleukin 3 (IL-3), fusion protein (FP), c-kit ligand (KL) or GM-CSF combined with other cytokines (KL, IL-3). Decreased colony forming units granulocyte-macrophage (CFU-GM) were detected in most cases (69%) compared with normal controls. Neither FP nor the combination of GM-CSF + IL-3 produced more colonies than GM-CSF alone. The number of CFU-GM did not correlate with French American British (FAB) class. All marrows (7) from patients with 5q- showed augmentation of GM-CSF induced colonies with the addition of KL. In contrast, KL augmentation was noted in only 42% of other MDS marrows (p = 0.01). This in vitro result suggests that 5q- may predict a group of MDS patients with a likelihood to respond to the combination of GM-CSF + KL.
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PMID:c-kit ligand augments granulocyte-macrophage colony growth from patients with 5q- syndrome. 750 25


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