Clinical Relevance of Differential RARα and PPARß/δ Expression in Myelodysplastic Syndromes.

BACKGROUND/AIM: Myelodysplastic syndromes (MDS) are clinically heterogeneous hematological malignancies with an increased risk of transformation to acute myeloid leukemia, emphasizing the importance of identifying new diagnostic and prognostic markers. This study sought to investigate the predictive ability of all-trans retinoic acid (ATRA)-dependent nuclear transcription factors RARα and PPARß/δ gene expression in MDS patients. MATERIALS AND METHODS: Peripheral blood specimens were collected from 49 MDS patients and 15 healthy volunteers. The specimens were further separated in Ficoll density gradient to obtain the mononuclear cells fractions. Gene expression analysis was carried out using quantitative real-time polymerase chain reaction (qRT-PCR) technique. RESULTS: In the mononuclear cell fractions of MDS patients, RARα expression was increased (p<0.05) and PPARß/δ expression was decreased (p<0.01) compared to healthy volunteers. When RARα and PPARß/δ expression was compared in groups of MDS patients with different risks of disease progression, no statistically significant difference was found for RARα expression, while PPARß/δ expression was significantly lower in the high-risk group of patients compared to the low-risk group (p<0.05). The expression of RARα was significantly associated with overall survival (p<0.05). ROC analysis showed that the expression of PPARß/δ, rather than RARα expression, could have potential diagnostic value for MDS patients (AUC=0.75, p=0.003 and AUC=0.65, p=0.081, respectively). CONCLUSION: RARα and PPARß/δ genes are putative biomarkers that may be associated with the diagnosis and prognosis of MDS.

Evaluation of VEGF and VEGFR gene expression as prognostic markers in low and intermediate­1 risk patients with myelodysplastic syndromes.

Vascular endothelial growth factors (VEGFs) are angiogenic factors playing a key role in tumor development. VEGFs are produced by different normal and tumor cells, including platelets, lymphocytes and mononuclear cells of peripheral blood. VEGF (VEGF-A, VEGF-C and VEGF-D) and VEGFR (VEGFR1, VEGFR2 and VEGFR3) gene expression was studied in patients with myelodysplastic syndrome (MDS) to evaluate the possible prognostic role of the expression of these genes. Gene expression levels were determined using peripheral blood samples of 51 patients with MDS and 15 healthy volunteers by quantitative PCR. Expression of all VEGF and VEGFR genes was elevated in patients with MDS compared with healthy volunteers. No association of VEGF-A expression with the hemoglobin content in peripheral blood was found. The analyses of gene expression in patients with MDS stratified by risk groups according to the International Prognostic Scoring System showed progressive augmentation of VEGF-A gene expression from low to high-risk groups and VEGFR1 and VEGFR2 expression from intermediate-1 to high-risk groups. The statistically significant difference in survival time of patients with high and low levels of VEGFR1 expression was revealed. VEGF-A/VEGFR1 expression may be important for risk evaluation of patients with MDS.

Regulatory T Cells and Profile of FOXP3 Isoforms Expression in Peripheral Blood of Patients with Myelodysplastic Syndromes.

We have investigated the frequencies of regulatory T cells and the level of FOXP3 isoforms expression in peripheral blood of patients with myelodysplastic syndromes and found the significant reduction of regulatory T cells at all stages of the disease. At the same time in untreated patients, we observed the shift in the FOXP3 isoforms expression profile towards the full-length molecule possibly due to inflammation. Based on the already known information about the potentially higher functional activity of FOXP3 molecule lacking exon 2, we have also hypothesized that our finding may explain the high risk of autoimmune disorders in this disease.