Construction of a microRNA-mRNA Regulatory Network in De Novo Cytogenetically Normal Acute Myeloid Leukemia Patients.

Background: The association between dysregulated microRNAs (miRNAs) and acute myeloid leukemia (AML) is well known. However, our understanding of the regulatory role of miRNAs in the cytogenetically normal AML (CN-AML) subtype pathway is still poor. The current study integrated miRNA and mRNA profiles to explore novel miRNA-mRNA interactions that affect the regulatory patterns of de novo CN-AML. Methods: We utilized a multiplexed nanoString nCounter platform to profile both miRNAs and mRNAs using similar sets of patient samples (n = 24). Correlations were assessed, and an miRNA-mRNA network was constructed. The underlying biological functions of the mRNAs were predicted by gene enrichment. Finally, the interacting pairs were assessed using TargetScan and microT-CDS. We identified 637 significant negative correlations (false discovery rate <0.05). Results: Network analysis revealed a cluster of 12 miRNAs representing the majority of mRNA targets. Within the cluster, five miRNAs (miR-495-3p, miR-185-5p, let-7i-5p, miR-409-3p, and miR-127-3p) were posited to play a pivotal role in the regulation of CN-AML, as they are associated with the negative regulation of myeloid leukocyte differentiation, negative regulation of myeloid cell differentiation, and positive regulation of hematopoiesis. Conclusion: Three novel interactions in CN-AML were predicted as let-7i-5p:HOXA9, miR-495-3p:PIK3R1, and miR-495-3p:CDK6 may be responsible for regulating myeloid cell differentiation in CN-AML.

Percentage of hypochromic red cells as a potential screening test to evaluate iron status in blood donors.

INTRODUCTION: Haemoglobin (Hb) levels are used to assess eligibility for blood donation but are not correlated with iron status. The percentage of hypochromic red cells (%Hypo-He) has been suggested as a useful screening parameter for iron deficiency. The aim of this study was to determine the cut-off level and accuracy of %Hypo-He screening among blood donors. MATERIALS AND METHODS: A total of 170 blood donors were recruited into the study. Blood donors were classified into three groups: normal, latent iron deficiency and iron deficiency anaemia based on their Hb, serum ferritin and transferrin saturation (TSAT) levels. The diagnostic performance of %Hypo-He was evaluated with a validation group comprising 160 blood donors. RESULTS: Receiver operating characteristic (ROC) curve analysis showed that %Hypo-He is an excellent parameter for detecting iron deficiency, with an area under the curve (AUC) of 0.906, a confidence interval (CI) of 0.854-0.957 at a cut-off of 0.6%, and 74.51% sensitivity and 88.24% specificity. A moderate negative correlation between %Hypo-He and TSAT (ρ = -0.576 [P < 0.001]) and a strong negative correlation between %Hypo-He and serum ferritin (ρ = -0.703 [P < 0.001]) were found. A cut-off value of 0.6% was applied to the validation group and showed 82.9% sensitivity and 96% specificity. CONCLUSION: %Hypo-He with a cut-off value of 0.6% is a potential parameter with high sensitivity and specificity for evaluating iron status among blood donors. This parameter is suitable for screening because its measurement has a faster turnaround time than biochemical markers.