Alterations in microRNA Expression during Hematopoietic Stem Cell Mobilization

Abstract

microRNAs play an important role in the regulation of gene expression, cell fate, hematopoiesis, and may influence the efficacy of CD34+ cell mobilization. The present study examines the role of hsa-miR-15a-5p, hsa-miR-16-5p, hsa-miR-34a-5p, hsa-miR-126-3p, hsa-miR-146a-5p, hsa-miR-155-5p, and hsa-miR-223-3p in the course of hematopoietic stem cell mobilization. The numbers of CD34+ cells collected in patients with hematological malignancies (39 multiple myelomas, 11 lymphomas) were determined during mobilization for an autologous hematopoietic stem cell transplantation. The miRNA level was evaluated by RT-PCR. Compared to baseline, a significant decline in hsa-miR-15a-5p, hsa-miR-16-5p, hsa-miR-126-3p, hsa-miR-146a-5p, and hsa-miR-155-5p was observed on the day of the first apheresis (day A). An increase was observed only in the expression of hsa-miR-34a-5p. On day A, a negative correlation was found between hsa-miR-15a-5p and hsa-miR-146a-5p levels and the number of CD34+ cells in peripheral blood. A negative correlation was observed between hsa-miR-146a-5p and the number of collected CD34+ cells after the first apheresis. Good mobilizers, defined according to GITMO criteria, demonstrated a lower hsa-miR-146a-5p level on day A than poor mobilizers. Patients from the hsa-miR-146a-5p "low expressors" collected more CD34+ cells than "high expressors". Our results suggest that the investigated miRNAs, especially hsa-miR-146a-5p, may influence the efficacy of HSC mobilization.

Keywords: CD34+; hematopoietic stem cells; hsa-miR-146a-5p; miRNA; mobilization; multiple myeloma.

Figure 1

Influence of miRNAs on individual signaling pathways in the marrow niche. The following ligand–receptor interactions play a key role in the HSC migration in the bone marrow niche: CXCL12 (SDF-1)/CXCR4, NOTCH1/JAG1 (Jagged-1), ANGPT1/ANGPT2/TEK (Tie-2), SPP1 (OPN)/CD44/integrin receptors, KITLG (SCF)/KIT (c-Kit), VEGFA (VEGF)/FLT1/KDR (VEGFR1/2), VCAM1/ITGA4 (VLA-4), and IGF1/IGF1R, which are significantly influenced by the selected miRNAs: hsa-miR-15a-5p, hsa-miR-16-5p, hsa-miR-126-3p, hsa-miR-146a-5p, hsa-miR-223-3p, hsa-miR-34a-5p, and hsa-miR-155-5p.

Figure 2

The comparison of the total number of CD34+ cells collected after mobilization at hsa-miR-146a-5p “low” and “high” expressors on the day of the first apheresis.

Figure 3

hsa-miR-146a-5p expression on the day of the first apheresis in patients divided into “good” and “poor” mobilizers according to GITMO criteria.

Figure 4

The kinetics of miRNAs expression at two time points: the day before HSC mobilization (day 0) and the day of the first apheresis (day A): hsa-miR-15a-5p, hsa-miR-16-5p, hsa-miR-126-3p, hsa-miR-146a-5p, hsa-miR-34a-5p, and hsa-miR-155-5p.