A miRNA Signature in Human Cord Blood Stem and Progenitor Cells as Potential Biomarker of Specific Acute Myeloid Leukemia Subtypes

Abstract

MicroRNAs (miRNAs) are important regulators of several cellular processes. During hematopoiesis, specific expression signatures have been reported in different blood cell lineages and stages of hematopoietic stem cell (HSC) differentiation. Here we explored the expression of miRNAs in umbilical cord blood stem (HSC) and progenitor cells (HPC) and compared it to unilineage granulocyte and granulo-monocyte differentiation as well as to primary blasts from patients with acute myeloid leukemia (AML). CD34 + CD38- ad CD34 + CD38 + cells were profiled using a global array consisting of about 2000 miRNAs. An approach combining bioinformatic prediction of miRNA targets with mRNA expression profiling was used to search for putative biologically enriched functions and networks. At least 15 miRNAs to be differentially expressed between HSC and HPC cell population, a cluster of 7 miRNAs are located in the q32 region of human chromosome 14 (miR-377-3p, -136-5p, 376a-3p, 495-3p, 654-3p, 376c-3p and 381-3p) whose expression decreased during the early stages of normal myelopoiesis but were markedly increased in a small set of AML. Interestingly, miR-4739 and -4516, two novel microRNA whose function and targets are presently unknown, showed specific and peculiar expression profile during the hematopoietic stem cells differentiation into unilineages and resulted strongly upregulated in almost all AML subsets. miR-181, -126-5p, -29b-3p and -22-3p resulted dis-regulated in specific leukemias phenotypes. This study provides the first evidence of a miRNA signature in human cord blood stem and progenitor cells with a potential role in hematopoietic stemness properties and possibly in leukemogenesis of specific AML subtypes.

MicroRNAs and tRNA-derived fragments predict the transformation of myelodysplastic syndromes to acute myeloid leukemia

“…Of note, 18 of the 23 differentially expressed miRNAs listed above have been previously identified in related AML studies. 14,18-20,49-58 Out of these 18 miRNAs, 15 showed identical directionality of the expression change (i.e. increased or decreased expression) when comparing AML to normal samples.…”

Comprehensive Analysis of MILE Gene Expression Data Set Advances Discovery of Leukaemia Type and Subtype Biomarkers

“…Furthermore, gene expression profiling was used to classify paediatric ALL subtypes by Yeoh et al [3]. Recently, apart from microarray technology for questions such as AML subtype determination [4], interest has been also turned towards searching for leukaemia biomarkers with miRNA [5–10] and lncRNA [11] analysis. Despite the existence of all those studies, there remains only one exceptional study which was conducted on a large scale to discriminate between all of the leukaemia subtypes [12].…”

DNA Methylation Targeting: The DNMT/HMT Crosstalk Challenge

“…In order to improve the activity and to reduce toxicity, this oligonucleotide is the subject of further studies in combination with other agents [58]. Another example of epi-miRNA is the oligonucleotide miR29b (Table 2, entry 8) that targets DNMT1, DNMT3a and DNMT3b, leading to a decrease of DNA methylation levels and the re-expression of TSGs [59,65,66,67]. …”