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

Results of our study on the activation of N-ras oncogene by point mutation in human leukemia and myelodysplastic syndrome have been described in this article. Point mutation was observed mainly on the 12th, 13th and 61st amino acid codon of ras genes. Therefore, oligomers containing mutations at these codons were used as probes for dot blot analysis of DNA derived from patient's bone marrow cells or leukemia cells. Polymerase chain reaction technique was used to amplify the DNA of ras genes containing 12th, 13th and 61st codons. By this technique, sensitivity of the method to detect the point mutations in ras oncogene was remarkably increased. Detection of the mutation in ras gene is considered to be very useful for the diagnosis, determination of remission and finding of relapse at an early stage. Study on the fused gene of bcr-abl, its mRNA and protein in chronic myelogenous leukemia is a good and reliable method to prove the existence of Ph1 positive chromosome by gene technology. Identification of the Ph1 acute lymphoblastic leukemia (ALL) has become possible by studying abl oncogene in Ph1 positive ALL. This method can be used also for the diagnosis of Ph1 ALL.
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PMID:[Oncogenes in human leukemia]. 265 Jun 33

A female patient received a renal transplantation from an unrelated cadaver donor, and five years later developed myelodysplastic syndrome (MDS) with immunological abnormalities. Chromosomal analysis showed trisomy 8 in bone marrow cells. FISH analysis indicated that trisomy 8 was present in 4% of CD19 + cells, suggesting that the MDS clone involved B lymphocytes. Polymerase chain reaction of the human androgen receptor gene indicated B cell clonality (54%) and granulocyte clonality (63%). There have been no previous reports of secondary MDS following renal transplantation in which the MDS clone involved the B cell lineage. The abnormal MDS B cell clone may have caused the immunological abnormalities.
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PMID:Myelodysplastic syndrome with B cell clonality in a patient five years after renal transplantation. 971 69

Polymerase chain reaction and single strand conformation polymorphism (PCR-SSCP) analysis of the p53 tumor suppressor gene (from exon 2 to 9) was performed on samples from 47 adult patients with primary myelodysplastic syndrome (MDS). Point mutation was found in 5 (11%) patients: exon 7 in 3, exon 4 in 1 and intron 5 in 1. The frequency of p53 mutation was significantly higher at advanced stages (p = 0.048) and higher in patients with abnormal karyotypes (p = 0.023). Although all of the p53 mutations were detected at advanced stages, four of them were detected at initial diagnosis with very short survival. Sequential SSCP analysis in 20 transformed MDS patients revealed only one new p53 mutation during progression from early MDS phases. The results suggest that p53 mutation might occur as an early genetic event and is probably associated with rapid progression and poor survival in some MDS patients.
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PMID:P53 mutation in advanced stage of primary myelodysplastic syndrome. 985 90

Background: Mutations in members of the ras gene family (H-ras, K-ras, and N-ras) have been identified in various human malignancies. A variety of techniques have been used to test for ras mutations. Methods and Results: A simplified reverse dot blot (RDB) assay was used in this study. Polymerase chain reaction products were hybridized to nitrocellulose membrane-fixed synthetic probes (20 nucleotides long) specific for codons 12, 13, and 61 of H-, K-, and N-ras mutations and their wild-type sequences. No special treatment or modification of the probes was necessary to obtain adequate results in overnight film exposure when the polymerase chain reaction was carried out using (32)P-end labeled primers. It was demonstrated that this simplified RDB assay can also be used with fluorescein-11-dUTP and a chemiluminescence detection system. The RDB assay is more reliable than the single-strand conformation polymorphism (SSCP) assay. By comparison, the SSCP assay is significantly less sensitive and less specific. It was confirmed with sequencing that 11 (12%) of 93 SSCP assays were false positive and 2 (2%) were false negative, whereas no false positive or false negative RDB assay was detected. The RDB assay also provides more additional detailed information about the specific point mutation and amino acid change, which may have clinical implications in some tumors. Conclusions: The RDB assay is very sensitive and able to detect mutations when the mutant allele is in 1% of the cells and can be used to detect minimal residual disease, particularly in some cases of leukemia and myelodysplasia.
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PMID:Simplified Reverse Dot Blot Analyses for Detecting of ras Oncogene Mutations. 1046 6

The proliferative and differentiative response of neutrophils to granulocyte-macrophage colony-stimulating factor (GM-CSF) is known to be impaired in patients with myelodysplastic syndromes (MDS). To investigate the mechanisms of the defective response in MDS, we examined expression levels of GM-CSF receptor alpha (GMR alpha) and common beta (beta c) subunits on CD16(+) neutrophils, CD14(+) monocytes and CD3(+) T cells from 26 MDS patients and 10 healthy controls using flow cytometry. Expression of GMR alpha was significantly decreased on the neutrophils of five out of 26 patients and was not specific for any FAB subtype. In contrast, beta c expression on neutrophils was significantly reduced in 14 out of 26 patients with a higher proportion occurring in the advanced stages of MDS including refractory anaemia with excess of blasts (RAEB), RAEB in transformation (RAEBt) and overt leukaemia compared with refractory anaemia (RA)/RA with ringed sideroblasts (RARS) or healthy controls. Decreased beta c also correlated with the degree of hypogranular neutrophil morphology and increased infection. Expression of both subunits on T cells and monocytes in MDS was similar to normal controls. Polymerase chain reaction amplification of reverse-transcribed mRNA isolated from the affected neutrophils suggests that the reduction of beta c may result from decreased message levels. The observed reduction in GM-CSF receptor expression could account for the impaired proliferative and maturational responses in MDS.
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PMID:Neutrophil-specific reduction in the expression of granulocyte--macrophage colony-stimulating factor receptor subunits in myelodysplastic syndromes. 1112 48

The ORC5L gene encoding a subunit of the human origin recognition complex (ORC) maps to chromosome band 7q22, a region frequently deleted in adult acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Because of its localization within a region that is commonly deleted in patients with myeloid malignancies and because of the implication of its protein product in cell cycle control (DNA replication) and regulation of gene expression (transcriptional silencing), ORC5L appeared to be a candidate tumor suppressor gene for myeloid disorders associated with 7q22 deletions. Polymerase chain reaction amplification and sequencing analysis of the coding region of the remaining ORC5L allele has not revealed any mutations in nine patients with AML or MDS exhibiting 7q22 deletions. Allelic expression analysis indicates that ORC5L is not imprinted. These data suggest that ORC5L does not function as a tumor suppressor in patients with myeloid neoplasms.
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PMID:Mutation analysis of the origin recognition complex subunit 5 (ORC5L) gene in adult patients with myeloid leukemias exhibiting deletions of chromosome band 7q22. 1137 76

Myelodysplastic syndromes (MDS) represent a group of clonal hematopoietic disorders characterized by dyshemopoiesis and frequent evolution to acute leukemia. Tumor suppressor gene inactivation may be involved in MDS pathogenesis. The two families of cyclin-dependent kinase inhibitors (CDKIs) (INK4 family of p15, p16, p18 and p19 and CIP/KIP family of p21, p27 and p57) that negatively regulate cell cycle progression are known tumor suppressor genes. To determine whether genetic alterations of p16 and p27 genes play an important role in MDS pathogenesis, we examined DNA from 51 patients classified as 17 refractory anemias (RA), four refractory anemias with ringed sideroblasts (RARS), 19 refractory anemias with an excess of blasts (RAEB), 5 refractory anemias with excess of blasts in transformation (RAEB-t) and 6 chronic myelomonocytic leukemias (CMML). Southern blot analysis detected no homozygous deletions of p16 and p27. Polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and sequencing did not reveal point mutations for both genes with the exception of two allelic polymorphisms, namely a C --> G transition at 447 bp of p16exon3 and a T --> A transition at 791 bp of p27exon1 genes. Our results suggest that mutations of p16 and p27 genes resulting in abnormal p16 and p27 proteins do not represent a mechanism of gene inactivation involved in the pathogenesis of MDS.
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PMID:Absence of p16 and p27 gene rearrangements and mutations in de novo myelodysplastic syndromes. 1610 74

Copy Number Aberration (CNA) in myelodysplastic syndromes (MDS) study using single nucleotide polymorphism (SNP) arrays have been received increasingly attentions in the recent years. In the current study, a new Constraint Moving Average (CMA) algorithm is adopted to determine the regions of CNA regions first. In addition to large regions of CNA, using the proposed CMA algorithm, small regions of CNA can also be detected. Real-time Polymerase Chain Reaction (qPCR) results prove that the CMA algorithm presents an insightful discovery of both large and subtle regions. Based on the results of CMA, two independent applications are studied. The first one is power analysis for sample estimation. An accurate estimation of sample size needed for the desired purpose of an experiment will be important for effort-efficiency and cost-effectiveness. The power analysis is performed to determine the minimum sample size required for ensuring at least (0<lambda <or=) detected regions statistically different from normal references. As expected, power increase with increasing sample size for a fixed significance level. The second application is the distinguishment of high-grade MDS patients from low-grade ones. We propose to calculate the General Variant Level (GVL) score to integrate the general information of each patient at genotype level, and use it as the unified measurement for the classification. Traditional MDS classifications usually refer to cell morphology and The International Prognostic Scoring System (IPSS), which belongs to the classification at the phenotype level. The proposed GVL score integrates the information of CNA region, the number of abnormal chromosomes and the total number of the altered SNPs at the genotype level. Statistical tests indicate that the high and low grade MDS patients can be well separated by GVL score, which appears to correlate better with clinical outcome than the traditional classification approaches using morphology and IPSS sore at the phenotype level.
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PMID:Pattern-selection based power analysis and discrimination of low- and high-grade myelodysplastic syndromes study using SNP arrays. 1935 88

More and more transcription factors and their motifs have been reported and linked to specific gene expression levels. However, focusing only on transcription is not sufficient for mechanism research. Most genes, especially in eukaryotes, are alternatively spliced to different isoforms. Some of these isoforms increase the biodiversity of proteins. From this viewpoint, transcription and splicing are two of important mechanisms to modulate expression levels of isoforms. To integrate these two kinds of regulation, we built a linear regression model to select a subset of transcription factors and splicing factors for each co-expressed isoforms using least-angle regression approach. Then, we applied this method to investigate the mechanism of myelodysplastic syndromes (MDS), a precursor lesion of acute myeloid leukemia. Results suggested that expression levels of most isoforms were regulated by a set of selected regulatory factors. Some of the detected factors, such as EGR1 and STAT family, are highly correlated with progression of MDS. We discovered that the splicing factor SRSF11 experienced alternative splicing switch, and in turn induced different amino acid sequences between MDS and controls. This splicing switch causes two different splicing mechanisms. Polymerase Chain Reaction experiments also confirmed that one of its isoforms was over-expressed in MDS. We analyzed the regulatory networks constructed from the co-expressed isoforms and their regulatory factors in MDS. Many of these networks were enriched in the herpes simplex infection pathway which involves many splicing factors, and pathways in cancers and acute or chronic myeloid leukemia.
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PMID:Discovering transcription and splicing networks in myelodysplastic syndromes. 2424 32

The aim of this study was to assess the possible influence of genetic polymorphisms in hOGG1, XRCC1, XRCC3, XPD, XPG and APE1 on the observed DNA damage in a group of Turkish myelodysplastic syndrome (MDS) patients. A total of 39 patients with myelodysplastic syndrome and 78 age-matched healthy control subjects were included in our study. Polymerase chain reaction/restriction fragment length polymorphism analysis was performed for the detection of DNA repair gene variants. No significant differences in DNA repair enzymes APE1, XRCC1 and XPG were found between MDS patients and controls. On the other hand, XRCC3, XPD and hOGG1 were associated with an increased risk of MDS (p=0.004, p=0.000, p=0.017, respectively). Specifically, Thr/Met genotype was more relevant in patients (p=0.026) in XRCC3; in hOGG1, Cys+ genotype was found higher in patients (p=0.017); and in XPD, Gln/Gln genotypes were found higher in the patient (p=0.001). In conclusion, XRCC3, XPD and hOGG1 genotypes are associated with an increased MDS risk, suggesting their possible involvement in the pathogenesis and biology of this disease.
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PMID:Investigation of DNA repair gene variants on myelodysplastic syndromes in a Turkish population. 2515 60


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