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

We present a case of myelodysplastic syndrome (MDS), which developed into an overt leukemic phase in a 15-year-old female with a rare constitutional abnormality [46,XX,t(2;11) (q31;p13)]. The patient entered complete remission after 3 months of chemotherapy. On chromosome analysis during remission, the t(2;11) (q31;p13) abnormality was detected in all metaphases of both the bone marrow cells and PHA-stimulated peripheral blood lymphocytes. Her father also had the same karyotype. This case seems to be of value as a reference for the study of the significance of constitutional chromosome abnormalities in MDS.
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PMID:Myelodysplastic syndrome in a patient with a unique constitutional chromosome abnormality t(2;11) (q31;p13). 139 10

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

A short-term 51Cr-release assay was employed to investigate polymorphonuclear leukocyte (PMN) antibody-dependent (ADCC) and phytohemaglutinin-induced (PHA-ICC) cytotoxicity against chicken erythrocytes in 28 patients with myelodysplastic syndromes (MDS). MDS patients PMN-mediated ADCC and PHA-ICC were significantly reduced when compared to normal donors. When the patients were subdivided according to the revised FAB classification, a reduction in PHA-ICC from the RAEB group and a progressive impairment of ADCC from RA to RAEB-t patients was observed. These abnormalities may be ascribed to a reduced number of effector cells or to a metabolic impairment of their cytolytic capacity. These PMN functional deficiences may contribute to the increased susceptibility to infectious diseases, irrespective of the presence of granulocytopenia.
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PMID:Defective antibody-dependent and lectin-induced polymorphonuclear cytotoxicity in patients with myelodysplastic syndromes. 233 86

We studied a group of patients with myelodysplastic syndromes (MDS) for surface markers and cytotoxic activities of peripheral blood mononuclear cells (PBMNC). The results indicate a significant increase in the total count of CD11b+, Leu7+ and CD16+ with a percent reduction in CD4+. A reduction in PHA-induced cellular cytotoxicity (PHA-ICC) and NK activity were found. A similar phenotype was found both in refractory anemia (RA) and (RA) with excess of blasts (RAEB/RAEB-t). However, the functional activities reached the normal level only in RA patients; while in RAEB/RAEB-t patients a significant reduction was detected in PHA-ICC and NK activity.
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PMID:Deficiency of lymphocyte lectin-dependent cytotoxicity in myelodysplastic syndromes. 250 68

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

In an agar-liquid double-layer colony assay in which myeloid leukemia colony-forming cells require the presence of both the lectin PHA and CSF for in vitro proliferation, colony formation of bone marrow cells derived from patients with a myelodysplastic syndrome (MDS) was studied. In five of 14 MDS and all five leukemic transformed MDS cases, colony formation was found to require both PHA and CSF. Three of these five PHA-dependent MDS cases progressed to overt leukemia within 1 year, one progressed from RA to RAEB, and one patient received AML chemotherapy. PHA-dependent colony formation was associated with higher bone marrow blast counts, but not directly to FAB type or cytogenetic abnormalities. In nine other MDS cases only CSF was required for colony formation. In these PHA-independent cases the course of the disease was stable during the observation time (5-17 months). Two types of colonies were observed in this in vitro system: colonies adherent and colonies nonadherent to the agar underlayer. The former consisted of terminally differentiated myeloid cells, and the latter comprised immature cells. This suggests that the percentage of adherent colonies formed in vitro may be used as a measure for the maturation defect in MDS. However, no correlation was found between the percentage of adherent colonies and progression to leukemia of the MDS cases. Our findings suggest that the dependency on PHA for in vitro colony formation of colony-forming cells in MDS is predictive for the progression to leukemia. However, the in vitro differentiation capacity has no apparent prognostic significance.
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PMID:In myelodysplastic syndromes progression to leukemia is directly related to PHA dependency for colony formation and independent of in vitro maturation capacity. 339 24

Previously, cloning efficiencies and mitogenic responsiveness of lymphocytes from patients with preleukemic disorders were shown to be significantly depressed. Whole blood T lymphocyte colony formation and 3H-TdR incorporation were used to assess the effects of interleukin-2 (IL-2) and thymopoietin (TP-5) on the proliferation of lymphocytes from patients with preleukemia. There were no statistically significant differences (p greater than 0.05) between any of the test groups stimulated with mitogen alone when compared to groups stimulated with mitogen plus TP-5 and/or IL-2 in either assay system for either patient or control groups. Nevertheless, TP-5 and IL-2 markedly increased the cloning efficiency and mitogenic responsiveness of lymphocytes from many of the patients studied, but in no case restored the proliferation response to the level of mitogen stimulated control lymphocytes. These findings suggest that other soluble mediators/factors may be needed to fully compensate for deficient mitogenic responsiveness and colony formation of lymphocytes from patients with preleukemic disorders which may be multifactoria in origin. Of importance, enhancement of lymphocyte responsiveness to PHA/Con-A with TP-5 and IL-2 suggests the presence of maturational/functional defects in lymphocytes from some of these patients which may be compensated for in part by addition of TP-5 and IL-2.
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PMID:Effect of thymopoietin and interleukin 2 on depressed mitogenic responsiveness and colony formation of lymphocytes from patients with preleukemia. 348 54

The producibility of interferon (IFN)-alpha, which indicates one of the functions of large granular lymphocytes (LGL), was impaired at a high frequency in myelodysplastic syndrome (MDS) patients. However, IFN-alpha production in refractory anaemia, which is a subtype of MDS, was almost normal. In contrast, abnormality has not been observed in either proliferative response or the production of IFN-gamma of T-cells by stimulation with PHA. NK activity of peripheral blood mononuclear cells (PBMC) from MDS patients was generally low and was not augmented by IFN-alpha treatment. These results indicate that, in addition to the abnormality at the level of haematopoietic tissues, LGL among PBMC may be impaired in MDS patients.
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PMID:Impaired alpha-interferon production and natural killer activity in blood mononuclear cells in myelodysplastic syndromes. 348 81

Bone marrow samples from 20 controls, 41 patients suffering from various types of myelodysplasia and 19 suffering from ANLL were investigated by in vitro cultures. The cultures were stimulated by various concentrations of leucocyte conditioned medium (LCM) and PHA-stimulated conditioned medium (PCM) and were examined after 7 and 14 d. We found that, in clinically stable MDS, growth patterns and dose-response to CM's were mostly within the normal range. With progressive blastic transformation, these features became abnormal with an increase in cluster growth. Clusters responding to a high dose of LCM, persisting after 14 d and enhanced by PCM may represent 'early' clonogenic cells. These clusters were found in progressive MDS with increased numbers of blast cells. Clusters formed by 'late' clonogenic cells were found in normal bone marrow and stable MDS. In ANLL the disturbance of proliferation and maturation seems to be much more pronounced than in progressive MDS with blastic transformation. We conclude that the interpretation of in vitro bone marrow culture data in terms of a disorderly arrangement of clonogenic cells in MDS and ANLL is facilitated by comparing different conditioned medium stimulations and by scoring after different time intervals.
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PMID:Significance of in vitro cultures in myelodysplastic syndromes. 349 52


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