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

Myeloid and erythroid progenitors from myelodysplastic marrows have been separated from accessory cell populations likely to influence their in-vitro growth. Myeloid colony-forming cells were enriched 23-fold and erythroid progenitors 5-7-fold but, in both cases, retained their abnormal growth characteristics. After enrichment and removal of lymphocytes and monocytes, erythroid burst formation became markedly more dependent on the addition of 5637 bladder carcinoma conditioned medium as an exogenous source of haemopoietic growth factors. This suggests that lymphocytes and monocytes usually support erythropoiesis in cultures of myelodysplastic marrow and demonstrates that erythroid burst-forming progenitor cells from myelodysplastic patients can respond to these populations in vitro. Haemopoietic failure in myelodysplasia appears to result from a defect within the preleukaemic clonogenic cell, rather than from an aberration in exogenous factors. The procedure outlined here can be used as a first step towards the isolation of these abnormal progenitors.
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PMID:Enrichment of haemopoietic progenitor cells from the marrow of patients with myelodysplasia. 328 3

Twenty-two of 35 patients with aplastic anaemia who received fetal liver infusion (FLI), responded to this treatment. Detailed review of bone marrow aspirates and biopsies was available in 17. There was a good correlation between clinical improvement and blood counts. The bone marrow cellularity increased to 48 percent in about 18 weeks with repopulation by both erythroid and myeloid cells. The erythroid response was predominant and the earliest to occur (1.5-61 weeks); it lasted for 7.5-100 weeks. Marked dyserythropoiesis was observed. Myeloid response occurred simultaneously in 45 percent of the responders; in the others it was delayed by 1.5 to 4 weeks. Significant dysmyelopoiesis with shift to the left, unrelated to infection, was seen 1.5 to 9.5 weeks after FLI lasting for 9-26 weeks in most cases. Megakaryocytic response either did not occur or was delayed, less marked and often transient.
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PMID:Bone marrow recovery following fetal liver infusion (FLI) in aplastic anaemia: morphological studies. 332 99

Monosomy 7 presenting as a myelodysplastic syndrome following radiation and chemotherapy has been reported to involve a stem cell capable of both erythroid and granulocyte/macrophage differentiation. To determine if monosomy 7 presenting de novo also involves a multipotential stem cell, we examined mitoses from individual colony-forming units (CFU)-GM and burst-forming units (BFU)-E colonies derived from semisolid cultures of marrow from an infant with this disorder. Direct cytogenetic analysis of bone marrow cells disclosed the characteristic 45,XY,-7 karyotype in 32 of 35 abnormal metaphases. Metaphases were obtained from 63 (73%) of 85 CFU-GM and BFU-E colonies (median metaphases per colony = 4, range = 1-21), with well-banded analyzable chromosome spreads available for 15 of the colonies with metaphases. The monosomy 7 karyotype was present in all 14 metaphases from ten BFU-E colonies and in all seven metaphases from five CFU-GM colonies. These results indicate that the monosomy 7 karyotype can originate in haematopoietic stem cells with both erythroid and granulocyte/macrophage differentiative potential.
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PMID:Cytogenetic evidence for involvement of erythroid and granulocyte/macrophage progenitors in an infant with monosomy 7 syndrome presenting de novo. 335 34

Pluripotent (CFU-MIX), erythroid (BFU-E) and granulocyte/macrophage (CFU-GM) progenitor cells were examined in bone marrow (BM) from 23 patients with myelodysplastic syndromes (MDS). Patients were grouped according to the FAB classification: Refractory anemia (RA), n = 3; RA with ring sideroblasts (RARS), n = 3; RA with excess of blasts (RAEB), n = 8; RA with excess of blasts in transformation (RAEBt), n = 7; chronic myelomonocytic leukemia (CMML), n = 2. In FAB groups RA, RARS, RAEB and RAEBt CFU-GM concentrations were normal or decreased but both CMML-patients had increased CFU-GM values. Abnormal cluster growth was observed in 9 of 23 MDS-patients. BFU-E colony formation was subnormal in all cases. Mixed-colony assay values were at the lower limit of controls in one patient and decreased in the remaining 22 MDS-patients. A similar growth pattern of hemopoietic progenitor cells was observed in 19 patients with acute nonlymphocytic leukemia (ANLL), who were studied for comparison. These data suggest a quantitative or qualitative/functional defect of the pluripotent progenitor cell compartment as the major cause for the cytopenia in MDS-patients.
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PMID:Deficiency of pluripotent hemopoietic progenitor cells in myelodysplastic syndromes. 339 Jun 17

A 6-year-old male with prior metastatic retinoblastoma developed a therapy linked myelodysplastic syndrome. Whole bone marrow cytogenetics showed monosomy 7 and a marker chromosome. To determine the progenitor level of origin of the malignant clone, we studied the karyotypes of marrow erythroid and granulocyte/macrophage colonies grown in methyl cellulose. All erythroid and granulocyte/macrophage colonies had an abnormal karyotype with 45 chromosomes (monosomy 7) and several colonies contained the marker chromosome. These findings give direct evidence that this patient's myelodysplastic syndrome involved an early stem cell which was capable of both erythroid and granulocyte differentiation.
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PMID:Cytogenetic evidence for involvement of erythroid progenitors in a child with therapy linked myelodysplasia. 346 43

The relation between prognosis and lineage specific surface antigen expression on peripheral blood granulocytes and monocytes was studied using monoclonal antibodies and flow cytometry in 37 patients with myelodysplastic syndromes (MDS). Abnormalities in antigen expression were summarised as a score, and cases were divided into low (few abnormalities) and high (many abnormalities) groups. Survival was significantly worse in the "high" group (logrank chi 2 = 5.793, p = 0.016), this group having a median survival of 31 weeks, compared with more than 67 weeks in the "low" group. No correlations were found between the score and any of the following: peripheral blood platelet and granulocyte count; FAB subtype; bone marrow blast cells and sideroblast count, or erythroid and myeloid progenitor growth. Antigen expression was also studied in six further cases of MDS before and after six weeks of treatment with 13-cis retinoic acid (CRA), 20 mg given orally, and a comparison was made with six untreated patients studied before and after a similar time interval. In the treated group 58% of initially abnormal measurements reverted to normal, compared with 24% in the untreated group. Five of the six treated patients showed a decrease in the score, whereas only two of the six improved in the untreated group. The data indicate that myeloid antigen expression is a useful indicator of prognosis in MDS, and that antigen expression may be affected by treatment.
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PMID:Myeloid surface antigen abnormalities in myelodysplasia: relation to prognosis and modification by 13-cis retinoic acid. 347 92

To determine the effects of the "maturation-inducing" agents 13-cis retinoic acid and 1,25 dihydroxyvitamin D3 on marrow cells from normal individuals and patients with myelodysplastic syndromes (MDS), we assessed marrow hemopoietic clonogenicity and differentiation response patterns to these agents. These vitamins caused increased proliferation in vitro of normal clonogenic marrow myeloid precursor cells (CFU-GM), decreased erythroid precursors (BFU-E), and no change in multipotent stem cells (CFU-GEMM). Marrow hemopoietic colony-forming cell incidence was generally subnormal in the 22 MDS patients evaluated. In vitro exposure to both agents caused various patterns of alteration of MDS hemopoietic colony and cluster formation, with similar but more pronounced effects evoked by retinoic acid. In the vast majority of MDS patients, enhanced marrow clonal granulocyte-monocyte differentiation and decreased BFU-E growth were noted after in vitro exposure to these vitamins. Correlation of biological effects was demonstrated between in vivo changes of peripheral neutrophil counts and in vitro responses of myeloid precursors for ten MDS patients treated with an eight-week therapeutic course of retinoic acid. Cytogenetic analyses indicated persisting aneuploidy or coexisting normal and aneuploid karyotypes in the cultured MDS myeloid cells and (with one exception) in native marrow cells from the treated patients. The varying responses of the MDS cells may monitor differing proportions of normal versus leukemic marrow cells susceptible to proliferative and differentiative expression on exposure to these agents.
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PMID:Responses of hemopoietic precursors to 13-cis retinoic acid and 1,25 dihydroxyvitamin D3 in the myelodysplastic syndromes. 351 68

Patterns of erythropoiesis and granulopoiesis were studied in 15 patients with myelodysplastic syndromes and in one with smouldering leukaemia by correlating CFU-C, BFU-E and CFU-E cloning efficiency with erythroid and myeloid maturation indices derived from quantitative 14C-autoradiography and with ferrokinetics. Maturation index of a cell lineage was defined as the ratio of cell production rate increase from the first to the last proliferative compartment over the corresponding normal value. The myeloid maturation index was reduced in all cases, but CFU-C progenitor frequency was increased by a factor of 3. Erythroid maturation index was also reduced in most cases, and BFU-E progenitor frequency was reduced by a factor of 2. Similarly, CFU-E cloning efficiency corrected for the erythroid maturation index was 2.5-10-fold lower than normal. Comparison of the erythroid maturation index with ferrokinetics revealed a constant ratio of ineffective erythropoiesis with a maturation disturbance in the proliferative pool twice that in the non-proliferative pool. These findings indicate basic qualitative and quantitative abnormalities and a difference in the patterns of production of erythroid and myeloid cells in the myelodysplastic syndromes: Myeloid progenitors are increased in number but their maturation is grossly abnormal. On the other hand, the apparent reduction in erythroid progenitors and the reduced erythroid maturation index are attributable to both premature cell death of the more mature erythroblasts and an increased proerythroblast proliferation, i.e. extra divisions in the proerythroblast compartment at the expense of maturation.
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PMID:Erythroid and myeloid maturation patterns related to progenitor assessment in the myelodysplastic syndromes. 366 22

Cell kinetics were studied by quantitative autoradiography in 29 patients with myelodysplastic syndromes (MDS) and in four with smouldering leukaemia (SML) in a prospective 6-year study. Cellular turnover in all FAB groups was characterized by reduced labelling index and prolonged DNA synthesis time indicating reduced proliferative activity. Two more parameters were derived from the measurements. (1) The relative cell production rate, which is increased in proerythroblasts and myeloblasts in most cases. This could be attributed to an increased number of divisions in early recognizable precursors in the absence of maturation, and (or) an increased influx from the progenitor compartments. (2) The maturation index of a cell lineage was determined by the ratio of relative cell production rate increase from the first to the last proliferative compartment over the corresponding normal value. It showed a high degree of abnormality in all FAB subgroups, indicating premature cell death in the bone marrow. None of the kinetic parameters proved to be of value in predicting the evolution of leukaemia. In contrast, an excellent correlation was found between the myeloid maturation index and survival (P less than 0.0001). No correlation, however, was found between survival and the erythroid maturation index, which was relatively normal in the worst prognostic group. These findings indicate that although in vitro cell kinetic studies can not predict the evolution of overt leukaemia, the myeloid maturation index is a useful predictor of survival in patients with MDS and SML.
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PMID:Mechanisms and prognostic value of cell kinetics in the myelodysplastic syndromes. 367 3

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


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