Differential Expression of MicroRNAs in CD34+ Cells of 5q- Syndrome

<p>Abstract</p> <p>Background</p> <p>Myelodysplastic syndrome with isolated chromosome 5q deletion (5q- syndrome) is a clonal stem cell disorder characterized by ineffective hematopoiesis. MicroRNAs (miRNAs) are important regulators of hematopoiesis and their aberrant expression was detected in some clonal hematopoietic disorders. We thus analyzed miRNA expressions in bone marrow CD34+ cells of 5q- syndrome patients. Further, we studied gene expressions of <it>miR-143</it>, <it>miR-145</it>, <it>miR-378 </it>and <it>miR-146a </it>mapped within the 5q deletion.</p> <p>Results</p> <p>Using microarrays we identified 21 differently expressed miRNAs in 5q- patients compared to controls. Especially, <it>miR-34a </it>was markedly overexpressed in 5q- patients, suggesting its role in an increased apoptosis of bone marrow progenitors. Out of four miRNAs at del(5q), only <it>miR-378 </it>and <it>miR-146a </it>showed reduced gene expression in the patients. An integrative analysis of mRNA profiles and predicted putative targets defined potential downstream targets of the deregulated miRNAs. The list of targets included several genes that play an important role in the regulation of hematopoiesis (e.g. <it>KLF4</it>, <it>LEF1</it>, <it>SPI1</it>).</p> <p>Conclusions</p> <p>The study demonstrates global overexpression of miRNAs is associated with 5q- phenotype. Identification of hematopoiesis-relevant target genes indicates that the deregulated miRNAs may be involved in the pathogenesis of 5q- syndrome by a modulation of these targets. The expression data on miRNAs at del(5q) suggest the presence of mechanisms for compensation of a gene dosage.</p

DNA repair gene variants are associated with an increased risk of myelodysplastic syndromes in a Czech population

Abstract Background Interactions between genetic variants and risk factors in myelodysplastic syndromes are poorly understood. In this case–control study, we analyzed 1 421 single nucleotide polymorphisms in 408 genes involved in cancer-related pathways in 198 patients and 292 controls. Methods The Illumina SNP Cancer Panel was used for genotyping of samples. The chi-squared, p-values, odds ratios and upper and lower limits of the 95% confidence interval were calculated for all the SNPs that passed the quality control filtering. Results Gene-based analysis showed nine candidate single nucleotide polymorphisms significantly associated with the disease susceptibility (q-value . Four of these polymorphisms were located in oxidative damage/DNA repair genes (LIG1, RAD52, MSH3 and GPX3), which may play important roles in the pathobiology of myelodysplastic syndromes. Two of nine candidate polymorphisms were located in transmembrane transporters (ABCB1 and SLC4A2), contributing to individual variability in drug responses and patient prognoses. Moreover, the variations in the ROS1 and STK6 genes were associated with the overall survival of patients. Conclusions Our association study identified genetic variants in Czech population that may serve as potential markers for myelodysplastic syndromes.</p

Low-dose cytosine arabinoside (LD-AraC) vs LD-AraC plus granulocyte/ macrophage colony stimulating factor vs LD-AraC plus Interleukin-3 for myelodysplastic syndrome patients with a high risk of developing acute leukemia: Final results of a randomized phase III study (06903) of the EORTC Leukemia Cooperative Group

SCOPUS: ar.jinfo:eu-repo/semantics/publishe