Abstract
Myelodysplastic syndromes (MDS) are a heterogeneous group of disorders characterized by ineffective hematopoiesis, defective differentiation of hematopoietic precursors, and expansion of the abnormal clones. The prevalence of MDS has raised great concerns worldwide, but its pathogenetic mechanisms remain elusive. To provide insights on novel biomarkers for the diagnosis and therapy of MDS, we performed high-throughput genome-wide mRNA expression profiling, DNA methylation analysis, and long non-coding RNAs (lncRNA) analysis on bone marrows from four MDS patients and four age-matched healthy controls. We identified 1,937 differentially expressed genes (DEGs), 515 methylated genes, and 214 lncRNA that showed statistically significant differences. As the most significant module-related DEGs, TCL1A, PTGS2, and MME were revealed to be enriched in regulation of cell differentiation and cell death pathways. In addition, the GeneGo pathway maps identified by top DEGs were shown to converge on cancer, immunoregulation, apoptosis and regulation of actin cytoskeleton, most of which are known contributors in MDS etiology and pathogenesis. Notably, as potential biomarkers for diagnosis of MDS, four specific genes (ABAT, FADD, DAPP1, and SMPD3) were further subjected to detailed pathway analysis. Our integrative analysis on mRNA expression, gene methylation and lncRNAs profiling facilitates further understanding of the pathogenesis of MDS, and may promote the diagnosis and novel therapeutics for this disease.
Highlights
Myelodysplastic syndromes (MDS) are a group of hemopathies featured with various degrees of ineffective hematopoiesis, and confer the host with inherent risk of progression to acute myeloid leukemia [1,2,3,4]
By analyzing the microarray data from four MDS and four control samples according to designed flowchart (Figure 1), we identified 1,937 differentially expressed genes (DEGs), 515 differentially methylated genes and 214 differentially expressed long non-coding RNAs (lncRNA)
28 of 214 lncRNAs have the record of transcripts
Summary
Myelodysplastic syndromes (MDS) are a group of hemopathies featured with various degrees of ineffective hematopoiesis, and confer the host with inherent risk of progression to acute myeloid leukemia [1,2,3,4]. The annual incidence of MDS is ∼3.5–10 per 100,000 in the general population, while 12–50 per 100,000 in elderly population [3, 4, 8]. The molecular characterization of MDS continues to be controversial, various studies demonstrated the clonal involvement of the myeloid lineages. The clonal mutation and expansion of abnormal myeloid cells are tightly associated with the dysfunction of pluripotent or multipotent hematopoietic cells, which may establish the MDS phenotype and determine natural disease course. The fundamentally complex genetic and biologic abnormalities in pathogenesis are demonstrated by the heterogeneity of the clinical and morphologic pictures of MDS [8]. The etiology and pathogenesis of MDS remain inadequately characterized
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