Distinctive microRNA expression profiles in CD34+ bone marrow cells from patients with myelodysplastic syndrome

Abstract

MicroRNAs (miRNAs) are small non-coding RNAs functioning as regulators of hematopoiesis. Their differential expression patterns have been linked with various pathological processes originating from hematopoietic stem cells (HSCs). However, limited information is available regarding the role of miRNAs in myelodysplastic syndrome (MDS). Using miRNA arrays, we measured expression of 1,145 miRNAs in CD34+ bone marrow cells obtained from 39 MDS and acute myeloid leukemia (AML) evolved from MDS patients, and compared them with those of six healthy donors. Differential miRNA expression was analyzed and a panel of upregulated (n¼13) and downregulated (n¼9) miRNAs were found (Po0.001) in MDS/AML patients. An increased expression of a large miRNA cluster mapped within the 14q32 locus was detected. Differences in miRNA expression of MDS subtypes showed a distinction between early and advanced MDS; an apparent dissimilarity was observed between RAEB-1 and RAEB-2 subtypes. In early MDS, we monitored upregulation of proapoptotic miR-34a, which may contribute to the increased apoptosis of HSCs. Patients with 5q deletion were characterized by decreased levels of miR-143* and miR-378 mapped within the commonly deleted region at 5q32. This is an early report describing differential expression in MDS CD34+ cells, likely reflecting their disease-specific regulation.

Microarray profiling defines circulating microRNAs associated with myelodysplastic syndromes

“…Expression of the selected miRNAs in CD34+ cells. Previously, we assessed miRNA signatures in CD34+ MDS cells through microarray profiling [10]. Here, we employed these data to evaluate the cellular levels of the plasma-related miRNAs (miR-16-5p, miR-27a-3p, miR-150-5p, miR-199a-5p, miR-223-3p, and miR-451a) with regard to patient prognosis.…”

“…Furthermore, we tested the myeloblastic cell population as another source of circulating miRNAs in MDS. We previously measured miRNA expression profiles in CD34+ MDS cells [10] (the majority of MDS myeloblasts are CD34+ [18]) and here we used these data to assess the correlation between cellular and plasma miRNA levels. However, the levels of plasma miRNAs did not reflect their levels in CD34+ cells.…”

Implication of microRNAs in the Pathogenesis of MDS

“…In a study by Dostalova Merkerova et al . (2011), miRNAs were isolated from CD34 + BM cells from 43 MDS patients and 9 healthy donors [93]. The patient cohort consisted of RA/RARS (n = 5), RCMD (n = 6), del(5q) (n = 6), RAEB (n = 17) and secondary AML (n = 9).…”

“…Thus, it is not surprising that certain miRNAs are also associated with MDS subtypes and risk groups. For example, Dostalova Merkerova and colleagues grouped patients into 5 common MDS categories [93]. Hierarchical clustering of 45 differentially expressed miRNAs distinguished 5q-syndrome, low-risk MDS (RA, RARS, and RCMD), high-risk MDS (RAEB−1/−2), and AML [93].…”

“…For example, Dostalova Merkerova and colleagues grouped patients into 5 common MDS categories [93]. Hierarchical clustering of 45 differentially expressed miRNAs distinguished 5q-syndrome, low-risk MDS (RA, RARS, and RCMD), high-risk MDS (RAEB−1/−2), and AML [93]. When applying IPSS risk stratification, miR-15a levels in BM samples were correlated to high-risk MDS, while miR-16 levels in PB were inversely associated with high-risk MDS [92] (Table 2).…”