Influence of Micrornas Expression in Graft-Versus-Host Disease After Allogeneic Transplantation.

MicroRNAs (miRNAs) are a family of 19–24 nucleotide noncoding RNAs, which affect the regulation of gene expression in eukaryotic cells by binding to a 3′-untranslated region which target messenger RNAs. MiRNAs play important roles in many cellular processes such as development, stem cell division, apoptosis and cancer. We profiled miRNAs expressed on patients who underwent allogeneic hematopoietic stem cell transplantation (HSCT).

Here we analyzed in a retrospective study 50 patients (pts) for miRNAs expression (miRNA-21; -128; -146; -155; and -181) in whole blood that underwent allogeneic HSCT and analyzed their outcome. MiRNA expressions were performed by miRNA-specific real time RT-PCR.

In this cohort 15 pts received grafts from HLA-identical siblings (30%), 25 pts from matched (50%) and 10 pts from mismatched (20%) unrelated donors. Transplantat consisted of unmanipulated peripheral blood stem cells (n=41, 82%) or bone marrow (n=9, 18%). Of all pts, 12 (24%) had relapsed and 3 (6%) died of February 2012. There was no significant correlation between miRNA expressions from siblings and unrelated donors. For miRNA-21, we found a moderate down-regulation in mismatched unrelated donors (p<0.08) versus matched donors. Analysis of each miRNAs for relapse or TRM showed no statistically differences. Among these pts, 45 (90%) developed acute GVHD (18 pts had an acute GvHD of grade ≥2). There was a trend correlation between low level of miRNA-181 (327 ± 117% vs. 537 ± 575%; p<0.07) and miRNA-128 (158 ± 92% vs. 297 ± 485%, p<0.06) of pts with acute GvHD ≥ 2. In pts with severe acute GVHD (grade >3) comparing all other pts, we found significant reductions of miRNA-146 (355% vs. 1526%, p<0.0001), miRNA-21 (904% vs. 5526%, p<0.001) and miRNA-155 (5.66% vs. 3.52, p<0.04). However, no statistic differences were found in the miRNA expressions in regards to chronic GVHD.

These results suggest that pts with low expression of miRNA-146, miRNA-21 and miRNA-155 confirms a relevant association of the development of acute GVHD and miRNA profilings could be an early indicator of severe acute GvHD.

No relevant conflicts of interest to declare.