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

Double minute chromosomes (dmin) are small chromatin bodies consisting of genes amplified in an extrachromosomal location. dmins are uncommon in hematologic malignancies; they are seen primarily in acute myeloid leukemia, with amplification of the MYC oncogene or, less frequently, the MLL transcription factor. Nine patients with hematologic malignancies with dmin were seen at the Roswell Park Cancer Institute between 1985 and 2000; eight had acute myeloid leukemia and one a myelodysplastic syndrome. Fluorescence in situ hybridization (FISH) demonstrated MYC amplification on dmin in four patients, but MLL amplification was not seen. Spectral karyotyping showed that the dmin derived from chromosome 11 in one patient and from chromosome 19 in two others without MYC or MLL amplification; derivation from these chromosomes was confirmed by FISH with chromosome paint probes. The dmin of chromosome 11 origin hybridized to a bacterial artificial chromosome (BAC) RP11-112M22 that maps to 11q24.3 and is predicted to contain ETS1 and other markers, including D11S11351 and D11S4091. The dmin of chromosome 19 origin in one patient hybridized to BACs RP11-46I12 and RP11-110J19; in the other patient, these clones did not hybridize with the dmin, but were found to be amplified on a marker chromosome that was derived from chromosome 19 in that patient's cells. These BACs have been mapped to 19q12-19q13.1 and 19q11-19q13.1, respectively, and are predicted to contain the markers D19S409 and D19S919 and the gene for ubiquinol-cytochrome C reductase, Rieske iron-sulfur polypeptide1 (UQCRFS1). dmin originating from chromosome 19 have not been reported previously in hematologic malignancies.
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PMID:Double minute chromosomes in acute myeloid leukemia and myelodysplastic syndrome: identification of new amplification regions by fluorescence in situ hybridization and spectral karyotyping. 1192 Dec 81

Gene expression profiling signatures may be used to classify the subtypes of Myelodysplastic syndrome (MDS) patients. However, there are few reports on the global methylation status in MDS. The integration of genome-wide epigenetic regulatory marks with gene expression levels would provide additional information regarding the biological differences between MDS and healthy controls. Gene expression and methylation status were measured using high-density microarrays. A total of 552 differentially methylated CpG loci were identified as being present in low-risk MDS; hypermethylated genes were more frequent than hypomethylated genes. In addition, mRNA expression profiling identified 1005 genes that significantly differed between low-risk MDS and the control group. Integrative analysis of the epigenetic and expression profiles revealed that 66.7% of the hypermethylated genes were underexpressed in low-risk MDS cases. Gene network analysis revealed molecular mechanisms associated with the low-risk MDS group, including altered apoptosis pathways. The two key apoptotic genes BCL2 and ETS1 were identified as silenced genes. In addition, the immune response and micro RNA biogenesis were affected by the hypermethylation and underexpression of IL27RA and DICER1. Our integrative analysis revealed that aberrant epigenetic regulation is a hallmark of low-risk MDS patients and could have a central role in these diseases.
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PMID:Genome-wide profiling of methylation identifies novel targets with aberrant hypermethylation and reduced expression in low-risk myelodysplastic syndromes. 2293 14

Mutations in the epigenetic regulator gene EZH2 are frequently observed in patients with myelodysplastic/myeloproliferative neoplasms (MDS/MPN; 10-13%) and are associated with a poor outcome. To gain more insight into EZH2 pathology, we sought to genetically characterize a cohort of 41 EZH2-mutated MDS/MPN patients using targeted deep next-generation sequencing (NGS), colony-forming progenitor assays and transcriptome analysis. Stable short hairpin RNA (shRNA)-mediated downregulation of EZH2 was performed in MDS-derived F-36P, MOLM-13 and OCI-M2 cells to study EZH2-specific changes. Targeted NGS revealed a complex pattern of mutations with a total of 190 individual mutations. EZH2 mutations frequently co-occur with TET2 (58%), RUNX1 (40%) and ASXL1 (34%) mutations. Colony assays indicated EZH2 mutations to be mostly early events in leukemogenesis and showed a complex mutational hierarchy. Gene expression data revealed a number of differently expressed genes between EZH2 wild-type and mutant patients including known EZH2 targets. Comparison of patient transcriptome to EZH2-downregulated cell line data revealed several genes as novel EZH2 targets, showing opposite as well as unidirectional regulation between cell lines and patients. Some genes, such as CXXC5, ETS1 and VAV3 have previously been implied to have a role in leukemogenesis. Their precise role in MDS/MPN needs to be further investigated.
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PMID:Molecular characterization of EZH2 mutant patients with myelodysplastic/myeloproliferative neoplasms. 2862 18