ABSTRACT
Wilms tumor 1 (WT1) has long been overexpressed in acute myeloid leukemia and has a prognostic value in its diagnosis.Lately, the formation of G-quadruplexes in oncogenic promoters like WT1 has been widely investigated since stabilizationof these structures leads to transcriptional inhibition of the oncogene. Daunorubicin and mitoxantrone considered as crucialcomponents of almost all standard acute myeloid leukemia induction regimens. Herein we have proposed a probablemolecular mechanism of action through which the drugs may stabilize WT1 promoter G-quadruplexes. Differential pulsevoltammetry, circular dichroism, and polyacrylamide gel electrophoresis, electrophoretic mobility shifts assay, polymerasechain reaction (PCR) stop assays, and quantitative RT-PCR were performed in order to better understanding the nature ofinteractions between the drugs and G-quadruplexes. Data revealed that both drugs had potential to stabilize G-quadruplexesand down-regulate WT1 transcription but daunorubicin exposed more silencing impact. The results illustrated the therapeutic association of these two commercial FDA-approved drugs in WT1 transcriptional down-regulation. Since WT1 hasknown as a transcriptional regulator of at least 137 target genes, so the new data are significant for the development of newapproaches to regulating WT1 and other target genes by employing special drugs in cancer treatment.
ABSTRACT
Background: Multiple myeloma is a conventional term for clonal proliferation of plasma cells. It is suggested that viruses may have a significant role in the pathogenesis of multiple myeloma. Aims: The aim of this study was to evaluate whether there is an association between multiple myeloma and Epstein-Barr Virus (EBV) by the polymerase chain reaction (PCR) method. Materials and Methods: This case-control study was performed on 60 paraffin-embedded bone marrow biopsies (30 multiple myeloma and 30 normal bone marrow specimens) in the molecular pathology section of our hospital. The patients and control groups were matched according to gender and age. Several sections were cut from each paraffin blocks, and then the deoxyribonucleic acid (DNA) was extracted by the non-heating extraction method. In the next step, PCR was carried out for detection of EBV genome and finally its products were analyzed by electrophoresis. Results: DNA of EBV was detected in 10 patients of the case group (5 males and 5 females) and 3 subjects (2 males and 1 female) of the control group. The Pearson chi-square test showed significant difference between case and control group (P=0.03) for detection of the EBV genome. In myeloma patients, the mean white blood cell count was 9.05 + 4.02 and 5.20 + 2.02 Χ 10 9 /L in EBV positive and negative groups, respectively and a significant difference count was seen for the WBC count. Recommendations: Our results show an association between multiple myeloma and EBV infection.