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)

We examined the efficacy of thalidomide in 34 patients with myelodysplastic syndromes (MDS): five RAEB-T, four RAEB, three CMML, six RARS, and 16 RA. Patients belonged to the following cytogenetic groups: 15 complex abnormal karyotypes, 12 normal karyotypes, four cases with 5q- as sole anomaly and three single aberrations. The median thalidomide dose was 400 mg/day (25/34 patients). Four patients discontinued the study after less than 5 weeks, because of fatigue (three) or skin rash (one). One patient died of heart failure after 4 weeks. In the remaining 29 patients (median follow-up: 13 months), treatment responses were classified according to the IWG criteria. Six patients (four RA, two CMML) showed progressive disease (five with transformation into AML) and four patients showed stable disease. Hematological improvement (HI) was observed in 19 patients. Nine of the responders (three RA, one RARS, two RAEB, three RAEB-T) achieved partial remission with granulocytes > or = 1500/microl, Hb > 11 g/dl and platelets > or =100,000/microl. Four patients (one RARS, one CMML, one RAEB, one RAEB-T) had a major response, with platelet and RBC transfusion independence. Six patients (five RA, one RARS) showed minor responses (three HI-E, two HI-E+HI-P, one HI-E+HI-N). Hematological improvement occurred after a median of 2 months of thalidomide treatment. Two patients (RAEB-T) relapsed after a partial remission lasting 8 and 16 months, respectively. In summary, a therapeutic benefit was achieved in 19 of 34 study patients (56%).
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PMID:Thalidomide for the treatment of patients with myelodysplastic syndromes. 1184 Feb 56

Blockade of tumor necrosis factor (TNF)alpha by a soluble TNF receptor fusion protein (etanercept; Enbrel) improved in vitro hemopoiesis from the marrow of patients with myelodysplastic syndrome (MDS). Therefore, we enrolled 14 MDS patients (4 RA, 2 RARS, 6 RAEB, 2 CMML), 44-80 (median 60) years old, in a pilot trial. Etanercept, 25 mg, was given twice a week s.c. for 16 weeks (increased to three times a week if no response at 8 weeks). Among 12 evaluable patients, four had rises in hemoglobin by 1-1.5 gm/dl (three) or decreased transfusion requirements (one). Two patients had increased platelet counts (54% and 73%), and two increased neutrophils (63% and 120%). Baseline TNFalpha levels, determined in all patients, did not correlate with responses. Among eight marrows available for sequential in vitro assays, four showed increases in CFU-GM of 1.5- to 5-fold at 8 weeks, whereas three showed 3- to 10-fold decrements relative to baseline. Thus, etanercept treatment resulted in moderate improvements of cytopenias in some patients, while cell counts declined in others. Additional trials are needed to evaluate its clinical efficacy in MDS.
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PMID:Soluble TNF receptor fusion protein (etanercept) for the treatment of myelodysplastic syndrome: a pilot study. 1184 Feb 80

Vitamin K2 is reported to induce apoptosis or differentiation of leukemic cell lines in vitro. We administered a vitamin K2 analog, menatetrenone, at 45 mg daily to 23 patients with myelodysplastic syndrome (MDS): 13 patients with RA, 2 with RARS, 6 with RAEB and 2 with RAEB-T. Good response (GR) and partial response (PR) were defined as an increase of hemoglobin concentration exceeding 2 g/dl and 1-2 g/dl without transfusion, respectively. Six of the RA patients showed improvement of anemia (GR, 3 patients; PR, 3 patients). RA patients who did not have a hypocellular bone marrow and were transfusion-independent tended to be responsive to vitamin K2 therapy in combination with vitamin D3 or anabolic steroids. No adverse effect of vitamin K2 was observed, and the time required to obtain the hematological response was short, being 3 months on average. We believe that vitamin K2 therapy has potential as a treatment for patients with MDS.
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PMID:[Vitamin K2 therapy for myelodysplastic syndrome]. 1192 74

A patient with a myelodysplastic syndrome ([MDS], i.e., refractory anemia with ring sideroblasts [RARS]) and a rapidly fatal clinical course is presented. A cytogenetic analysis showed an isochromosome 17q as a sole abnormality in all metaphases. An association between RARS and i(17q) has not been reported. Furthermore, a mutation of the remaining TP53 gene in exon 6 was evidenced by a single strand conformation polymorphism technique. This unique case illustrates heterogeneity of phenotypic expression of a stem cell disorder in MDS and indicates precaution in classifying hematologic syndromes especially when morphology is correlated with specific cytogenetic changes.
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PMID:Refractory anemia with ring sideroblasts associated with i(17q) and mutation of the TP53 gene. 1260 40

Myelodysplastic syndromes (MDSs) are heterogeneous diseases of bone marrow (BM) cell precursors for which immunophenotypic characterization is still considered irrelevant despite the accuracy and sensitivity of flow cytometry techniques. The aim of this study was to determine whether immunophenotypic abnormalities could be defined in MDSs and could correlate with the French-American-British classification and cytogenetics. Analysis was performed on 275 BM samples (207 MDS patients, 68 controls) and 25 control blood samples. Immunophenotyping was based on a primary gating of blast cells, monocytes, and granulocytes according to CD45 antigen expression and side scatter light diffraction. Immunophenotypic hierarchical clustering was performed to analyze the results. The data obtained show that (1) immunophenotypic clustering partly discriminates patients with refractory anemia with excess blasts/refractory anemia with excess blasts in transformation (RAEB/RAEB-T), chronic myelomonocytic leukemia (CMML), and refractory anemia/refractory anemia with ring sideroblasts (RA/RARS) for CD45(lo) blast cells and patients with RA/CMML, RARS, and RAEB/RAEB-T for CD45(hi)/side scatter(hi) (SS(hi)) granulocytes; (2) the most discriminating markers were CD16, CD34, CD36, CD38, CD71, and HLA-DR for blast cells and CD11b, CD13, CD33, CD36, CD38, CD71, and HLA-DR for CD45(hi)/SS(hi) granulocytes; (3) clusters related to CD34 expression were associated with high levels of blast cells on BM smear; (4) clusters related to high levels of CD36 expression on CD45(lo) blast cells and CD45(hi)/SS(hi) granulocytes were associated with a poor International Prognosis Scoring System score; and (5) high levels of CD71 expression on CD45(hi)/SS(hi) granulocytes were associated with the RARS category. These results show a close relationship between immunophenotypic abnormalities and BM dysplasia and suggest that flow cytometry could be a future tool for the characterization of MDSs.
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PMID:Immunophenotypic clustering of myelodysplastic syndromes. 1223 42

Low-risk myelodysplastic syndromes (MDS), including refractory anemia and sideroblastic anemia, are characterized by increased apoptotic death of erythroid progenitors. The signaling pathways that elicit this pathologic cell death in MDS have, however, remained unclear. Treatment with erythropoietin in combination with granulocyte colony-stimulating factor (G-CSF) may synergistically improve the anemia in patients with MDS, with a concomitant decrease in the number of apoptotic bone marrow precursors. Moreover, we have previously reported that G-CSF inhibits Fas-induced caspase activation in sideroblastic anemia (RARS). The present data demonstrate that almost 50% of erythroid progenitor cells derived from patients with MDS exhibit spontaneous release of cytochrome c from mitochondria with ensuing activation of caspase-9, whereas normal erythroid progenitors display neither of these features. G-CSF significantly inhibited cytochrome c release and suppressed apoptosis, most noticeably in cells from patients with sideroblastic anemia. Furthermore, inhibition of caspase-9 suppressed both spontaneous and Fas-mediated apoptosis of erythroid progenitors in all low-risk MDS cases studied. We propose that the increased sensitivity of MDS progenitor cells to death receptor stimulation is due to a constitutive activation of the mitochondrial axis of the apoptotic signaling pathway in these cells. These studies yield a mechanistic explanation for the beneficial clinical effects of growth factor administration in patients with MDS, and provide a model for the study of growth factor-mediated suppression of apoptosis in other bone marrow disorders.
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PMID:Granulocyte colony-stimulating factor inhibits spontaneous cytochrome c release and mitochondria-dependent apoptosis of myelodysplastic syndrome hematopoietic progenitors. 1239 61

Myelodysplastic syndrome (MDS) is a clonal disorder of hematopoietic stem cells. To investigate whether chromosomal instability and/or DNA repair defects are involved in the development of MDS, we measured the micronucleus (MN) frequency in peripheral blood lymphocytes exposed to various doses of X-rays, using a cytokinesis-block micronucleus assay. The spontaneous MN frequencies in RAEB and RAEB-T patients were significantly higher than those in normal individuals (P = 0.0224, P = 0.008, respectively). Also, the X-ray-induced MN frequencies in RA/RARS, RAEB, and RAEB-T patients were significantly higher than those in normal individuals (P = 0.007, P = 0.003, P = 0.003, respectively, at 2 Gy). In order to elucidate the cause of unusual radiosensitivity, we measured the expression levels of nucleotide excision repair (NER) genes in peripheral blood mononuclear cells using a RT-PCR method. Reduction of NER gene expression was found in only one of 10 patients with low risk MDS, but in four of 11 patients with high risk MDS. Our data suggest that chromosomal instability and DNA repair defects may be involved in the pathophysiology of disease progression of MDS.
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PMID:Chromosomal instability and radiosensitivity in myelodysplastic syndrome cells. 1239 70

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

In 31 patients of myelodysplastic syndrome, RAEB-t was the commonest subtype (29%), and RARS, the lease common (6.4%); 19.4% were characterised as the unclassifiable (UC) group. Pallor was the dominant sign (90.3%). Low haemoglobin in RA & RARS (p<0.05), thrombocytopenia in RAEB-t (p<0.01) and high leuco/monocyte counts in CMML (p<0.001) were observed. Neutropenia occurred most frequently in RAEB & RAEB-t and circulating blasts in all cases of RAEB-t and CMML. Bicytopenia was the commonest finding (58.1%) and pancytopenia the least (16.1%). 84% of marrows were hypercellular and trilineage dysplasia was seen in 68% of patients. Megaloblastoid dyserythropoiesis was the predominant feature in all cases, dysgranulopoiesis in all cases of RAEB, RAEB-t and CMML, and micromegokaryocytes in all cases of RARS, RAEB & CMML were seen. RAEB-t and RAEB (33.3% each) were the predominant groups which progressed to leukemia, FAB AML-M2, being the commonest type (60%).
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PMID:A study of the haematologic spectrum of myelodysplastic syndrome. 1256 87

We retrospectively studied 227 patients with MDS (1) to identify the prognostic factors of survival and acute leukemia evolution in Korean patients with MDS, (2) to apply different prognostic scoring systems to the same group of patients, and (3) to compare the FAB with the WHO classification. Six scoring systems were applied to the patients, and the FAB and WHO classifications were compared. The patients' median age was 57 years. The median survival time was 21 months, and age, dysgranulopoiesis and the IPSS cytogenetic groups were independent prognostic factors for survival. Acute leukemia occurred in 34 patients, and the cumulative incidence was 27.1% at 3 years. Marrow blast percentage was the only independent prognostic factor for acute leukemia evolution. Most scoring systems successfully discriminated risk groups for survival and acute leukemia evolution, but patient distribution into risk groups varied according to the scoring systems. Refractory cytopenia with multilineage dysplasia and RAEB II seemed to have different prognoses from RA or RARS and RAEB I, respectively. In summary, our MDS patients had different disease natures from those of Western countries regarding clinical features, prognostic factors and cytogenetic profiles. Although the WHO classification seems to improve the FAB classification, further studies are warranted to validate the utility of the WHO classification before it is accepted for routine clinical use. Our study has the limitations of retrospective analysis, and our results should be verified in future prospective studies.
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PMID:Application of different prognostic scoring systems and comparison of the FAB and WHO classifications in Korean patients with myelodysplastic syndrome. 1259 27


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