Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026986 (myelodysplastic syndrome)
 14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We attempted to identify the cytogenetic significance in predicting the prognosis of patients with myelodysplastic syndrome (MDS). From the results, we established scoring system (Bournemouth scoring+cytogenetic scoring: 3 for > or = 3 chromosomal abnormalities; 1 for -7/7q-, +8, 2 abnormalities); patients with score of > or = 5 had significant worse prognosis than that with score 0-2. Moreover, RARS with complex abnormalities consists of specific subtype showing a high leukemic rate with a high mortality rate. MDS with hypocellular marrow showed prognosis similar to those with typical MDS, while those with minimal dysplasia had prognosis similar to those with aplastic anemia. Patients with MDS were categorized into 3 subtypes, i.e., early disease-evolution, late disease-evolution, and no disease-evolution group. About 50% of patients with complex abnormalities showed early disease-evolution, while the remaining died before disease-evolution. In patients showing late disease-evolution, no cytogenetic factor are informative to predict the timing of disease-evolution, except percentage of marrow blasts at the diagnosis.
 ...
PMID:[Clinical implications of chromosome analysis in myelodysplastic syndrome]. 847 77

This paper reports on the production of tumor necrosis factor (TNF) and granulocyte macrophage colony-stimulating factor (GM-CSF) by cultured mononuclear adherent cells derived from bone marrow of 25 patients affected by myelodysplastic syndrome (MDS) of different FAB subtypes. Mean production of GM-CSF was much lower than in controls, without significant differences among different subtypes. Mean production of TNF was similar in MDS patients and in controls, but noteworthy differences were observed between patients with RA, RAEB and RAEB-t and patients with RARS and CMML. Growth of bone marrow granulocyte macrophage and erythroid progenitors did not correlate with TNF and GM-CSF production, although in MDS subtypes with higher GM-CSF levels, colony growth was slightly higher than in subtypes with lower GM-CSF production.
 ...
PMID:Producton of tumor necrosis factor and granulocyte colony stimulating factor by bone marrow accessory cells in myelodysplastic patients. 859 33

Myelodysplastic syndrome (MDS) comprises a group of heterogeneous clonal bone marrow disorders leading to peripheral cytopenia(s) and hypercellular marrow in the majority of the patients. The morphology of the cell lines is characterized by dysplastic features in some or all cell lines. The FAB classification has divided MDS in five subgroups, namely (1) RA (refractory anemia); (2) RARS (refractory anemia with ring sideroblasts); (3) CMML (chronic myelomonocytic leukemia); (4) RAEB (refractory anemia with excess blasts); and (5) RAEB-T (refractory anemia with excess blasts in transformation). Myelodysplastic syndrome remains primarily a disease of the elderly. With a reported median age of 74.4 years, patients have a chronic relentless course with complication of cytopenias, and a significant number of MDS patients, especially from the RAEB and RAEB-T categories, end up in acute myeloid leukemic transformation. Cytogenetic abnormalities are present in 40-58% of the cases and can provide not only help in diagnosis, but also understanding regarding the clinical course and prognostic aspect. Management of MDS is quite pragmatic and at this stage far from satisfactory. Various modalities have included use of differentiating agents, aggressive chemotherapy, bone marrow transplant and, more recently, significant interest has been generated in the use of hematopoietic growth factors. Differentiating agent trials have been unrewarding so far; chemotherapy trials have resulted in less benefit and more early toxic deaths, especially in the elderly MDS patients where the disease predominates. Bone marrow transplant appears suitable for some patients who are at a younger age. Salvation from this disease is being searched in the proper usage of hematopoietic growth factors and cytokines. There has been concern, however, that usage of growth factors has led to early and enhanced transformation of these patients to frank acute leukemic states. This concept appears to be somewhat refuted by newer controlled trials with GM-CSF and G-CSF, emphasizing that the acute leukemic transformation is the natural course of the disease and is not hastened by growth factor use. Preliminary studies are also suggesting that a combination of growth factors, especially G-CSF and erythropoietin as compared to chemotherapies, could be more beneficial in prolonging the survival of MDS patients who have progressed to the acute leukemic phase. More studies are needed for the understanding of the pathogenetic mechanism(s) in order to facilitate a more suitable and appropriate management strategy for MDS.
 ...
PMID:Myelodysplastic syndromes in the elderly: the role of growth factors in management. 863 15

We retrospectively reviewed 62 MDS patients (15 RA, 3 RARS, 10 CMML, 20 RAEB, 14 RAEBT) to clarify the current problems in their management. Median survival of RA and RARS patients was 67.9 months and significantly longer than that of CMML, RAEB, or RAEB-T patients with median survivals of 16.1, 16.8, and 9.5 months, respectively. Karyotypic abnormalities were observed in 58% of the patients examined. Forty-two patients died, 16 (38%) of leukemic transformation and 21(50%) of bone marrow failure. While most of the RAEB-T patients of all ages and all the RAEB patients diagnosed below 60 years of age died of transformation, 70% of the older RAEB patients died of infection. Prognosis after transformation was poor and 12 patients died within two months. These results indicate that management after transformation and treatment against infection in RAEB patients with advanced age are crucial to improve the prognosis in MDS.
 ...
PMID:Prognostic implications in myelodysplastic syndromes: A review of 62 cases. 917 14

Apoptosis of hematopoietic progenitor cells is increased in myelodysplastic syndromes (MDS). We have studied Fas (CD95/Apo-1) antigen expression in 27 MDS patients (RARS 4, RA 3, RAEB 13; RAEB-t 3, CMML 4) and three AML secondary to MDS. We found that the Fas antigen was not expressed on normal bone marrow (BM) CD34+, CD14+, or glycophorin+ cells, and only slightly on CD33+ cells. Patients with MDS had upregulation of Fas expression on total bone marrow nuclear cells (BMMC) (t-test, P = 0.04), CD34+ (P = 0.013), CD33+ (P = 0.04), and glycophorin+ (P = 0.032) BM cells compared to controls. Fas expression did not correlate to the FAB subtype, the Bournemouth score, or to peripheral cytopenias. However, Fas expression intensity on CD34+ cells negatively correlated to the BM blasts number (Spearman, P = 0.01) suggesting that leukemic blasts cells lose Fas antigen expression with progression of myelodysplasia. Using both proliferation assays in liquid cultures and clonogenic progenitor assays in the presence of an agonist anti-Fas MoAb (CH11), we showed that the Fas protein was functional in some patients. Dose-dependent inhibition of DNA synthesis was observed in three out of seven patients studied. CFU-GM and BFU-E colonies suppression in some patients suggested that Fas can induce apoptosis in myeloid and erythroid BM progenitors of MDS patients. The TUNEL technique on BM smears gave a mean of 12.6% +/- 2.5 of bone marrow apoptotic cells in five controls. Patients with MDS had increased bone marrow apoptosis (mean 39% +/- 5.7, t-test, P = 0.012). Four out of 15 (26%) patients studied with a sensitive radiolabeled DNA ladder technique had typical DNA ladders indicative of advanced stages of apoptosis. Massive BM suicide was observed in patients with RA (2/2) and RAEB (8/11), whereas apoptosis rates were normal or low in patients with RAEB-t (3/3) or secondary AMLs (3/3). Moreover, high rates of apoptosis correlated to low Bournemouth score (Spearman, P = 0.01). No statistical correlation could be found between Fas expression and apoptosis rates. Our results confirm the importance of programmed cell death in MDS. The Fas antigen is clearly upregulated on BM cells, but its role in the pathophysiology of apoptosis in myelodysplasia is still unclear, indicating that many factors positively or negatively interfere with the Fas-mediated pathway of apoptosis in vivo and in vitro.
 ...
PMID:Fas/Apo-1 (CD95) expression and apoptosis in patients with myelodysplastic syndromes. 917 38

Previous studies have shown that the cyclin-dependent kinase inhibitor (CDKI) genes p15INK4B and p16INK4A are frequently inactivated by genetic alterations in many malignant tumors and that they are candidate tumor-suppressor genes. Although genetic alterations in these genes may be limited to lymphoid malignancies, it has been reported that their inactivation by aberrant methylation of 5' CpG islands may be involved in various hematologic malignancies. In this study, we investigated the p15INK4B and p16INK4A genes to clarify their roles in the pathogenesis of myelodysplastic syndrome (MDS). Southern blotting analysis showed no gross genetic alterations in either of these genes. However, hypermethylation of the 5' CpG island of the p15INK4B gene occurred frequently in patients with MDS (16/32 [50%]). Interestingly, the p15INK4B gene was frequently methylated in patients with high-risk MDS (refractory anemia with excess blasts [RAEB], RAEB in transformation [RAEB-t], and overt leukemia evolved from MDS; 14/18 [78%]) compared with patients with low-risk MDS (refractory anemia [RA] and refractory anemia with ring sideroblast [RARS]; 1/12 [8%]). Furthermore, methylation status of the p15INK4B gene was progressed with the development of MDS in most patients examined. In contrast, none of the MDS patients showed apparent hypermethylation of the p16INK4A gene. These results suggest that hypermethylation of the p15INK4B gene is involved in the pathogenesis of MDS and is one of the important late events during the development of MDS.
 ...
PMID:Hypermethylation of the p15INK4B gene in myelodysplastic syndromes. 926 57

Previous studies have shown that approximately 40% of patients with myelodysplastic syndrome (MDS) and anaemia respond to treatment with human recombinant granulocyte-CSF (G-CSF) plus erythropoietin (epo). The present study was designed to investigate pre-treatment variables for their ability to predict erythroid responses to this treatment. 98 patients with MDS (30 RA, 31 RARS, 32 RAEB, five RAEB-t) were treated with a combination of G-CSF (0.3-3.0 microg/kg/d, s.c.) and epo (60-300 U/kg/d, s.c.) for at least 10 weeks. Minimum criteria for erythroid response was a 100% reduction of red blood cell (RBC) transfusion need or an increase in haemoglobin level of > or = 1.5 g/dl. 35 patients (36%) showed responses to treatment. Medium duration of response was 11-24 months. In multivariate analysis, serum erythropoietin levels and initial RBC-transfusion need retained high statistical significance (P < 0.01). Using pre-treatment serum epo levels as a ternary variable (< 100, 100-500 or > 500 U/l) and RBC transfusion need as a binary variable (< 2 or > or = 2 units per month), the analysis provided a predictive score for erythroid response. This score divided patients into three groups: one group with a high probability of erythroid responses (74%), one intermediate group (23%) and one group with poor responses to treatment (7%). This predictive scoring system could be used in decisions regarding use of these cytokines for treating the anaemia of MDS, both for defining patients who should not be given the treatment and for selecting patients for inclusion in prospective trials.
 ...
PMID:Erythroid response to treatment with G-CSF plus erythropoietin for the anaemia of patients with myelodysplastic syndromes: proposal for a predictive model. 937 52

Allogeneic bone marrow transplantation (BMT) offers a potential cure for younger patients with myelodysplastic syndromes (MDS) or secondary acute myeloid leukemia (sAML). More than 600 patients from 50 European centers have now been reported to the European Group for Blood and Marrow Transplantation (EBMT). We retrospectively analyzed 131 patients reported to the Chronic Leukemia Working Party of the EBMT who underwent BMT from HLA-identical siblings without prior remission induction chemotherapy. At the time of BMT 46 patients had refractory anemia (RA) or RA with ringed sideroblasts, 67 patients had more advanced MDS subtypes and 18 patients had progressed to sAML. The 5-year disease-free (DFS) and overall survival (OS) for the entire group of patients was 34 and 41%, respectively. Fifty patients died from transplant-related complications, most commonly graft-versus-host disease and/or infections. Relapse occurred in 28 patients between 1 and 33 months after BMT, resulting in an actuarial probability of relapse of 39% at 5 years. DFS and OS were dependent on pretransplant bone marrow blast counts. Patients with RA/RARS, RAEB, RAEB/T and sAML had a 5-year DFS of 52, 34, 19 and 26%, respectively. The 5-year OS for the respective patient groups was 57, 42, 24 and 28%. In a multivariate analysis, younger age, shorter disease duration, and absence of excess of blasts were associated with improved outcome. From these data we conclude that patients with myelodysplasia who have appropriate marrow donors, especially those aged less than 40 years and those with low medullary blast cell count should be treated with BMT as the primary treatment early in the course of their disease. Transplantation early after establishing the diagnosis of MDS may improve prognosis due to a lower treatment-related mortality and a lower relapse risk.
 ...
PMID:Bone marrow transplantation from HLA-identical siblings as first-line treatment in patients with myelodysplastic syndromes: early transplantation is associated with improved outcome. Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation. 948 48

A cytogenetic and N-ras point mutation study was done in patients with primary myelodysplastic syndrome (MDS) from Rio de Janeiro, Brazil, in order to evaluate the progression of preleukemic states to overt leukemia. Cytogenetic analysis was performed in 50 patients with MDS and clonal chromosomal abnormalities were detected in 19 (38%) of them. Patients with refractory anemia (RA) or with ringed sideroblasts (RARS) presented normal karyotypes or single abnormalities as del(5q) or -Y, while patients in more advanced states as RA with excess of blasts (RAEB), RAEB in transformation (RAEB-t) and chronic myelomonocytic leukemia (CMML) showed complex karyotypes and single abnormalities involving chromosomes 7 or 8, which were related to poor prognosis and elevated risk of transformation to acute myeloid leukemia (AML). The frequency of ras activation was studied in these 50 patients with MDS. Samples of bone marrow were screened for oncogenic point mutations by DNA amplification followed by oligonucleotide hybridization analysis (PCR-ASO) at codon 12 of N-ras proto-oncogene. We detected N-ras point mutations in 21 patients (42%). Progression from MDS to AML was observed in 9 patients (18%). The correlation analysis between N-ras point mutations and specific chromosomal abnormalities indicated that although mutated N-ras was found in cells with del(5q) and monosomy 7, cells with those abnormalities and normal N-ras were also identified. Otherwise trisomy of chromosome 8 showed a correlation with N-ras point mutations and in all cases, patients showed progression of MDS to AML during the follow-up study. MDS comprises a heterogeneous group of hematopoietic disorders and probably several steps are implicated in the evolution to AML. In this work we suggest that one possible pathway of leukemogenesis in MDS includes N-ras point mutations in association with trisomy of chromosome 8.
 ...
PMID:Correlation of N-ras point mutations with specific chromosomal abnormalities in primary myelodysplastic syndrome. 959 69

We present the case of a patient with MDS RARS subtype with loss of part of the long arm of chromosome 11 del 11(q23). This a cytogenetic abnormality that occurs in 7% to 20% of RARS cases not related to poor prognosis. It seems that this deletion is a marker of iron overload in MDS.
 ...
PMID:del 11(q23) as a prognostic factor of iron overload in refractory anemia with ringed sideroblasts. 959 17


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>