Comparative Analysis of Quantitative Parameters of Expression of the Retinoic Acid Nuclear Receptor RARα Gene and APE1/YB-1/MDR1 Pattern Genes in Patients with Newly Detected Multiple Myeloma.

The expression of retinoic acid nuclear receptor gene RARα and its relationship with expression of APE1, YB-1, and MDR1 genes was studied in bone marrow aspiration biopsy specimens from 22 patients with newly detected multiple myeloma. The expression of RARα directly correlated with the expression of APE1/YB-1/MDR1 pattern genes. Groups differing by expression of RARα exhibited significant differences in the overall survival of patients; concordant and simultaneous changes in the expression of all genes of the APE1/YB-1/MDR1 pattern suggested the level of RARα gene expression as a potential prognostic factor in the pathogenesis of multiple myeloma.

[Analysis of VEGF-A/VEGFR1/VEGFR2 gene expression in patients with myelodysplastic syndrome]. / Analiz ékspressii genov VEGF-A/VEGFR1/VEGFR2 u patsientov s mielodisplasticheskim sindromom.

AIM: To assess the significance of gene expression of the vascular endothelial growth factor-A (VEGF-A) and its interacting receptors VEGFR1 and VEGFR2 as potential diagnostic and prognostic molecular markers in patients with myelodysplastic syndrome (MDS). MATERIAL AND METHODS: A real time polymerase chain reaction (RT-PCR) assay was used to investigate the gene expression of VEGF-A, VEGFR1, and VEGFR2 in the mononuclear cell fractions obtained from 24 patients with MDS. RESULTS: The expression of the 3 genes was identified in all the patients examined. There was the highest expression level of the VEGF-A gene (p<0.0001), whereas the expression of the VEGFR1 gene was higher than that of the VEGFR2 gene (p<0.001). The expression of the VEGF-A gene proved to be higher in patients at a higher risk of acute leukemia and positively correlated with the expression levels of the VEGFR1 gene (p<0.05) rather than that of the VEGFR2 gene. At the same time, patients with higher VEGFR1 gene expression had significantly lower overall survival rates (r=-0.5; p<0.05). Patients with intermediate-2 or high-risk acute leukemia showed an increase in the average expression levels of VEGF-A and VEGFR1 and a reduction in VEGFR2 expression. CONCLUSION: This investigation revealed correlations between the number of blast cells in patients with MDS and the expression levels of the VEGF-A gene and between the overall survival of patients with MDS and the expression levels of the VEGFR1 gene rather than those of the VEGF-A and VEGFR2 genes.

[Gene expression of key enzymes for all-trans- retinoic acid biosynthesis - ALDHJAI and RDH10: relationship with co-expression of nuclear receptors RARα and PPARß/δ genes and some clinical characteristics in multiple myeloma.

The significance of quantitative changes of ALDH1A1 and RDH10 gene expression in 22 non-treated multiple myeloma patients were studied. We found a direct correlation between the expression of ALDH1A1 and RDH10 genes. We showed that ALDHA1 and RDH10 expression were inversely related with expression of a key gene for all-trans-retinoic acid catabolism, CYP26A1, and correlated with expression of RARα and PPARß/ genes. In addition for the first time it was re- vealed that increased expression of ALDH1A1-RDH10-RARα- PPARß/δ pattern could be considered as adverse prognostic factor associated with a higher concentration of paraprotein and worst overall survival of patients with newly diagnosed multiple myeloma.

[The significance of expression of isoforms RARa1 and RARa2 in response to medicinal therapy and in evaluation of total survival of patients with primarily detected multiple myeloma].

Introduction: The RARa is a transcription factor playing important role in such processes as proliferation, differentiation and apoptosis of cells in norm and in tumor. At the same time, it is little known about significance of expression of two major products of transcription of gene RARa - isoforms RARa and RARa - in pathogenesis of solid and non-solid tumors, including multiple myeloma. The actual data testify ambiguity of input made by isoforms RARa and RARa into processes of tumor development and progression of malignant tumors. The results: It was established that higher level of expression of isoform RARa in combination with increased expression of isoform RARß (group 1) statistically reliable associated with lesser decreasing of concentration of Bence Jones protein in urine of patients in the result of applied treatment and, therefore, lesser effectiveness of response to standard treatment according protocol M-2 in comparison with group II which included patients with lesser levels of expression of RARa and RARß (32.8% and 62.8% for groups I and II correspondingly; p=0.037). The analysis of indices of survival of examined patients in groups I and II demonstrated that median of total survival of patients from group I was reliably lower than in patients included into group II (30 and 84 correspondingly; p=0.046). Conclusion: The results of study demonstrate that increased level of expression in the first instance of isoform RARa in combination with hyper-expression of isoform RARß but not RARa can have unfavorable significance in case of evaluation of response to medicinal therapy and prognosis of total survival in patients with multiple melanoma.

[Differential expression ß2 and ß4 isoforms of retinoic acid receptor gene RARß as possible prognostic factor in multiple myeloma].

In this study, for the first time the expression of ß2 and ß4 isoforms of RARß gene was investigated in group of 19 patients with the newly diagnosed multiple myeloma. The expression of both RARß2 and RARß4 isoforms was detected in all patients, but it was different and had opposite tendency. We showed that RARß4 expression level positively correlated with VEGF-A and VEGFR1 expression levels. It was found that higher levels of RARß4/VEGF-A/VEGFR1 co-expression were defined of patients with statistically significant increase of plasma cell level and paraprotein concentration. The median overall survival was lower in patients with RARß4, over-expression, while the maximal median overall survival was observed of patients with RARß2 down-regulation and nearly absolute RARß4inactivation.

Expression of vascular endothelial growth factor receptors VEGFR1 in cultured multiple myeloma cells: correlation with immunophenotype and drug resistance.

We studied the expression of genes encoding vascular endothelial growth factors VEGF-A, VEGF-C, VEGF-D and their receptors in cell cultures of human multiple myeloma IM9, RPMI 1640, RPMI 8226. The studied cells did not differ by the expression of growth factors. Expression of VEGFR1 receptor was detected only in IM9 cells and VEGFR2 and VEGFR3 receptors were not expressed in multiple myeloma cells. A dependence between the aberrant CD45/CD56 phenotype of human multiple myeloma cells and VEGFR1 expression in them was revealed. The only VEGFR1-positive IM9 cell culture was most resistant to Velcade (bortezomib).