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)

The in vitro growth of circulating erythroid progenitors (BFU-E) populations and the production of burst-promoting activity (BPA) by T lymphocytes have been studied in 17 patients with myelodysplastic syndromes. Based on the in vitro growth patterns of BFU-E, four groups of patients have been identified: i) normal BFU-E growth; ii) low spontaneous BFU-E growth, but normal response to LCM; iii) impaired BFU-E response to LCM; iv) no BFU-E growth. The pattern of BFU-E growth seems to be related to the clinical stage of the disease rather than to the FAB subgroup to which the patients belong. The ability of T lymphocytes to stimulate BFU-E growth was significantly reduced in all patients. The possible mechanisms inducing the impaired production of BPA by T lymphocytes are discussed. The in vitro evaluation of circulating erythroid precursors can supply useful prognostic information and possibly indications concerning the responsiveness of erythropoietic stem cells to recombinant human erythropoietin in vivo.
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PMID:In vitro growth of erythroid progenitor cells (BFU-E) and production of burst-promoting activity (BPA) by T lymphocytes in patients with myelodysplastic syndromes. 129 50

The myelodysplastic syndrome (MDPS) provides an opportunity for identifying host factors (genetic, endocrine, immune) involved in initiation and progression of preleukemia into frank acute myeloid leukemia. The aim of this study was to identify bone marrow (BM) cellular and humoral dysfunctions central to the development of MDPS and useful in therapeutic follow-up studies. Our preclinical studies have shown that (1) the characteristic stromal cell composition of the normal BM microenvironment was impaired in MDPS and in AML in 67 and 86% of the cases, respectively; (2) the 1 alpha,25(OH)2D3 concentration in BM plasma was abnormal in 50% of MDPS and 30% of AML; and (3) an inverse correlation existed in MDPS between the 1 alpha,25(OH)2D3 concentration and the frequency of F-CFU, (r = 0.41, p < 0.02), suggestive of a regulatory interaction between this secosteroid hormone and BM stromal cells. The analysis of clonal extinction of BM blast cells in response to all trans retinoic acid (RA), 1 alpha,25(OH)2D3, and colony stimulating factors (PHA-LCM), either alone or in various combinations, revealed individual patterns of responses in the cases of MDPS or AML. The results indicate the necessity for preclinical studies to select patients for combined differentiation therapy. Our ongoing clinical trials suggest that RA (Roaccutan, 20 mg/day continuously) as induction therapy, followed at weeks 6 to 8 by prednisone (40 mg/day for 15 days) and 1 alpha,25(OH)2D3 (Rocaltrol, 3 x 0.25 micrograms/day for 3 months) may induce a long-lasting hematological remission in MDPS.
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PMID:Combined differentiation therapy in myelodysplastic syndrome with retinoid acid, 1 alpha,25 dihydroxyvitamin D3, and prednisone. 145 17

The in vitro effect of recombinant human GM-CSF (rHuGM-CSF) was tested on bone marrow-derived multilineage (CFU-GEMM) as well as megakaryocytic (CFU-Mk), erythroid (BFU-E), and granulocyte-macrophage (CFU-GM) progenitors in a group (n = 16) of patients with myelodysplastic syndromes (MDS). Hematopoietic progenitor cell growth was markedly impaired in MDS patients as compared to normal controls (p less than 0.05, at least). Recombinant HuGM-CSF supported the growth of CFU-GEMM, CFU-Mk, and BFU-E at lower, equivalent, or slightly higher frequencies that those found in cultures plated with medium conditioned by peripheral blood leukocytes (PHA-LCM), but it was invariably ineffective in improving growth values. Recombinant HuGM-CSF supported the growth of granulocyte-macrophage colonies in 15 of 16 cases. The overall incidence (mean +/- SEM) of CFU-GM in cultures containing rHuGM-CSF (5 ng/ml) was significantly higher than the one found in cultures stimulated with PHA-LCM (40 +/- 15 vs. 17 +/- 7, p less than 0.05). Upon culture with rHuGM-CSF (5 ng/ml), in 5 of 15 patients de novo colony formation was observed (8 +/- 4) and in 4 of 15 patients CFU-GM growth (129 +/- 33) fell within normal range. Doses of rHuGM-CSF higher than 5 ng/ml did not result in a further increase of MDS-derived colony formation. It is concluded that rHuGM-CSF (a) does not improve the growth of CFU-GEMM, CFU-Mk, and BFU-E; (b) may completely restore the growth of CFU-GM in a subgroup of MDS patients; (c) while ineffective in improving anemia and thrombocytopenia, its in vivo in MDS may correct leukopenia through an effect at the level of granulocyte-macrophage progenitor cell compartment, at least in a subset of highly responsive patients.
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PMID:Growth of human hematopoietic colonies from patients with myelodysplastic syndromes in response to recombinant human granulocyte-macrophage colony-stimulating factor. 265 96

The ability of plasma from myelodysplastic patients to support the clonal growth of normal megakaryocyte progenitors (CFU-Mk) was compared with that of plasma from normal subjects. The resultant megakaryocyte colonies were expressed as a plasma factor index megakaryocyte (PFI-Mk). All cultures included PHA-LCM and medium conditioned by the human bladder carcinoma cell line 5637, and some of them had EPO. PFI-Mk (MDS) was significantly lower than PFI-Mk (normal), both with and without EPO. A positive correlation was found between megakaryocyte and platelet count in normal subjects, but was not present in MDS patients. There was no correlation between platelet count and PFI-Mk in neither group. In MDS there was a negative correlation between megakaryocyte number and PFI-Mk, both with and without EPO. Although, the mean megakaryocyte number in MDS and in normal bone marrow was similar, the proportion of immature megakaryocytes was much higher in MDS. Previous work indicates an abnormal clonal origin of megakaryocytes in MDS. The present study suggests that abnormal plasma factors affects megakaryocytopoiesis in this condition.
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PMID:Stimulation of CFU-Mk colony growth by normal plasma and plasma from myelodysplastic patients. 270 75

The in vitro growth characteristics of a large series of acute myeloid leukaemia (AML) patients and their relationship with other clinical and biological disease characteristics were analysed. Patients with AML were studied, 181 with de novo AML and 45 with secondary AML (24 myelodysplastic syndrome, sAML-MDS, 21 myeloproliferative disorder, sAML-MPD). Leukaemic colony forming units (L-CFU) were assayed by plating peripheral blood (PB) blast cells in methyl-cellulose and using LCM-PHA as stimulant. In each case parallel cultures were made with and without stimulating factors. Plating efficiency (PE) was defined as the number of clusters plus colonies/10(5) cells plated. Autonomous growth (AG) was the number of colonies plus clusters growing without stimulant. The autonomous proliferative index (API) was calculated as the number of clusters + colonies without stimulating factor divided by the number of clusters + colonies with stimulating factor. No significant differences in the PE between de novo and secondary AML were found. Autonomous growth was significantly higher in sAML-MPD. The FAB subtype M3 leukaemias displayed a significantly greater PE and a significantly lower API when compared with the other FAB subgroups (P=0.0002). Upon analysing the relationship with the immunophenotype, only CD33 expression showed a significant relationship with the in vitro growth pattern; CD33+ cases displayed a higher PE (P=0.0002) and AG (P=0.0003) than CD33- cases. When patients were grouped according to the level of rh123 efflux (MDR1) it was observed that cases with >30% elimination showed a higher AG and API than those with <30% (P=0.03). Finally we found that patients with higher API (>0.05) displayed a significantly shorter overall survival as compared with patients with API<0.05 (P=0.04). The in vitro study properties of clonogenic cells produces relevant clinical information of leukaemic cell biology in AML patients.
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PMID:In vitro growth in acute myeloblastic leukaemia: relationship with other clinico-biological characteristics of the disease. 979

Biological and clinical significance of growth pattern of hematopoietic progenitors were investigated in 117 patients with primary myelodysplastic syndromes (MDSs) at referral. Abnormal (i.e., "leukemic" or absent) growth of GM colonies (CFU-GM) and GM clusters was found in 47% of patients with "advanced" MDS (RAEB, RAEB-t, and CMML) and in 15% of "low-risk" (RA/RARS) patients. In vitro erythropoiesis was decreased in most of the patients, with significantly lower number of BFU-E in "advanced" MDS than in RA/RARS patients. Megakaryocyte progenitors (CFU-MK) were very low or absent in almost all the patients, regardless of the FAB type. Significant correlation was demonstrated between the number of BFU-E and hemoglobin concentration and between number of CFU-MK and platelet count. Growth capacity of GM progenitors appears to be in proportion to "myeloproliferative" capacity of the malignant clone. T-cell depletion had no influence on growth capacity of hematopoietic progenitors, nor did colony growth respond in a dose-dependent manner to different concentrations of LCM. Growth capacity of MDS hematopoietic progenitors was independent of Bournemouth score, of the presence and type of cytogenetic abnormality, and of the expression of CD95 and caspase-3 antigens on bone marrow cells. However, in patients with "abnormal" growth of GM progenitors, CD34 antigen expression was significantly higher than in patients with "normal" growth. "Abnormal" GM growth was found to be independently predictive regarding the survival and the risk for AML development. In contrast, the prognostic value of erythroid and megakaryocyte cultures was found to be limited.
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PMID:Biological and clinical significance of clonogenic assays in patients with myelodysplastic syndromes. 1251 19