Investigating the role of MİR-146a in TGF-β signal regulation in myelodysplastic syndrome and leukemias and its relationship with 5q deletion

Myelodysplastic syndrome (MDS) is a clonal heterogeneous hematopoietic stem cell malignancy characterized by dysplastic cells and cytopenia in peripheral blood due to inefficient hematopoiesis. Clonal chromosomal abnormalities are seen in 30-50% of patients. However, a large number of gene mutations and miRNAs with altered gene expression have been associated with MDS. In order to establish an association between the cytogenetic and molecular findings in patients included in our study, we focused on the deletion of 5q, which is one of the most frequenly deleted regions in MDS, and the expression levels of miR-146a / miR-145 encoded from this region. The association between the MDS, miRNAs and SMAD2, a target of the above mentioned miRNAs and a functional gene in the signaling pathway of TGF- β, a suppressive cytokine, was investigated. A total of 24 bone marrow aspiration materials obtained from patients pre-diagnosed with MDS and the blood of 20 healthy control subjects were investigated using cytogenetic, FISH and RT-PCR methods. Clonal cytogenetic abnormality was detected in 43.4% of the cases and del (5q) abnormality was evaluated using cytogenetic and FISH methods but no statistically significant deletion finding was found in cases. miRNA expression analysis showed that the expression of miR-146a was decreased in all patients (p = 0.0003) while SMAD2 expression was increased in 41.6%. While there was no statistically significant change in miR-145 and SMAD2 expression levels, a significant relationship between these two was found (p = 0.04). Increasing the number of patients may help to enlighten the molecular pathogenesis of MDS.