Investigating the Expression Pattern of the SETMAR Gene Transcript Variants in Childhood Acute Leukemia: Revisiting an Old Gene.

BACKGROUND: The chimeric enzyme SETMAR (or Metnase) has been associated with several DNA processes, including DNA damage repair through the non-homologous joining pathway and suppression of chromosomal translocation in mouse fibroblasts. SETMAR overexpression has been reported in certain cancers suggesting that it might contribute to the establishment or progression of these cancers. In leukemia, the SETMAR gene transcript variants have not been widely studied. Therefore, this study aimed to quantify 3 predominant SETMAR variants in 2 types of childhood acute leukemia, acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). METHODS: In this study, using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), the relative expression of 3 SETMAR transcript variants (Var 1, Var 2, and Var A) were evaluated in the bone marrow samples collected from 30 newly diagnosed patients with AML, 65 newly diagnosed patients with ALL, and 15 healthy individuals. RESULTS: The expression of SETMAR variants 1 and A were significantly higher in AML patients compared with controls ( P =0.02, and P =0.009, respectively). Variant A expression was significantly higher in ALL compared with controls ( P =0.003). When comparing the expression in translocation-positive and negative subgroups, the expression of variant 1 was significantly higher in translocation-positive ALL patients ( P =0.03). The variants' distribution patterns differed concerning translocation status ( P =0.041), as variants 1 and A were dominant in the translocation-positive ALL group, and variant 2 was more prevalent in translocation-negative ones. CONCLUSIONS: According to the results, SETMAR showed increased expression in pediatric acute leukemia's bone marrow samples, indicating a role for this molecule in leukemia pathogenesis. As this is the first report of SETMAR expression in pediatric leukemias, further studies are needed to investigate the causality of this association.

Expression of DR4, DR5, FAS, Caspase-8 and, DDIAS Genes in AML Patients.

Background: Acute myeloid leukemia (AML) is the most common acute leukemia in adults and accompanies a worse survival. In this study, gene expression levels of 5 key players of apoptosis, including DR4, DR5, FAS, caspase 8, and DNA damage-induced apoptosis suppressor (DDIAS), have been evaluated in AML patients compared with controls, aiming to evaluate their possible role and prognostic impact. Methods: This cross-sectional study was performed in the Cancer Molecular Pathology Research Center, Mashhad University of Medical Sciences. A total of 30 newly diagnosed AML cases as well as 30 healthy controls enrolled in the study. Real-time polymerase chain reaction was used to evaluate the expressions of DR4, DR5, FAS, DDIAS, and caspase 8 genes in cases and controls. Other necessary data, including cytogenetic findings, mutations, French-American-British (FAB) classification, and survival, were retrieved from hospital records and by direct contact with patients. Statistical analysis was done by SPSS software. When appropriate, the Mann-Whitney U, Pearson's correlation, and the t tests were utilized. Overall survival (OS) was estimated using the Kaplan-Meier method. Results: The expression of all evaluated genes, including DDIAS (0.89 ± 0.20), DR4 (0.67 ± 0.24), DR5 (0.72 ± 0.24), FAS (0.70 ± 0.25), and Caspase 8 (0.77 ± 0.20) were significantly decreased in AML patients compared with the controls (P < 0.001). Patients with the t (16;16) or inv (16) expressed significantly higher amounts of the FAS gene and those with FLT3 mutation exhibited lower expression of caspase 8. Expression of the evaluated genes showed no significant effect on survival. Conclusion: The expression of DR4, DR5, FAS, and caspase 8 seems to be decreased in AML. Lower expression of these molecules may aid AML cells in avoiding apoptosis because they are involved in the initiation of apoptosis, making them potential targets for treatment.

Evaluating the frequency, prognosis and survival of RUNX1 and ASXL1 mutations in patients with acute myeloid leukaemia in northeastern Iran.

To evaluate the frequency and prognosis of runt-related transcription factor 1 (RUNX1) and additional sex combs like-1 (ASXL1) mutations in acute myeloid leukaemia (AML) patients in northeastern Iran. This cross-sectional study was performed on 40 patients with AML (including 35 patients with denovo AML and five patients with secondary AML) from February 2018 to February 2021. All patients were followed up for 36 months. We evaluated the frequency and survival rate of RUNX1 and ASXL1 mutations in AML patients. To detect mutations, peripheral blood samples and bone marrow aspiration were taken from all participants. One male patient (2.5%) had RUNX1 mutations and four cases (10%; 3 females vs. 1 male) had ASXL1 mutations. The survival rates of AML patients after 1, 3, 6, 9, 12, 24 and 36 months were 98%, 90%, 77%, 62%, 52%, 27% and 20%, respectively. There was a significant relationship between the occurrence of ASXL1 mutations and the survival of patients with AML (p = 0.027). Also, there was a significant relationship between the incidence of death and haemoglobin levels in patients with AML (p = 0.045). Thus, with an increase of one unit in patients' haemoglobin levels, the risk of death is reduced by 16.6%. Patients with AML had a high mortality rate, poor therapy outcome and low survival rate. ASXL1 and RUNX1 mutations are associated with a worse prognosis in patients with newly diagnosed AML. Also, we witnessed that the prevalence of ASXL1 to RUNX1 mutations was higher in northeastern Iran compared with other regions.

Deregulation of the Expression of Beclin1 and Light Chain 3(LC3), Autophagy-Related Genes, in COVID-19 Patients.

Background: The autophagy machinery is reported to be employed by Coronaviruses during their replication. Beclin-1 (BECN1) and protein 1 light chain 3 (LC3) are two key elements in the autophagy process, and their inhibition can prevent the replication of some coronaviruses in vitro. Here, we aimed to investigate the expression levels of Beclin-1 and LC3 in COVID-19 patients and healthy controls, hoping to find new therapeutic targets. Methods: This cross-sectional study was conducted in Imam Reza and Ghaem University Hospitals, Mashhad, Iran. Nasopharyngeal samples of 68 consecutive Covid-19 patients and 61 healthy controls, who have been referred to the laboratories for COVID-19 PCR testing between 21 March to 21 September 2021, were used in order to evaluate the expression of BECN1 and LC3 genes using the Real-time quantitative PCR method. Demographic and other laboratory findings of patients were extracted from the hospital electronic system. SPSS Statistics 16.0 and Graph Pad Prism 8.4.2 soft wares were used for statistical analysis. Non-parametric tests were used. Results: BECN1 expression was significantly higher in COVID-19 patients compared to the controls (14.37±18.84 vs. 4.26±7.39, p=0.001). The expression of LC3 gene was significantly lower in patients compared to the controls (1.01±1.06 vs. 1.49±1.12, p=0.007). There was no significant correlation between the expression levels of BECN1 and LC3. Patients with lower BECN1 expression showed significantly higher RBC counts, higher Urea and lower HCO3 levels. The patients in LC3Low group showed significantly lower MCH, MCHC and PH levels compared to the others. Conclusion: Regarding the significant difference in the expression of BECN1 and LC3 in COVID-19 patients compared to the controls, these molecules may have a role in the pathogenesis of this disease. In case of further confirmation of this role, these molecules may be used as possible therapeutic targets.

Relation of hepcidin gene expression in blood mononuclear cells with iron overload severity among ß-thalassemia major patients.

Iron overload is the main cause of morbidity and mortality in ß-thalassemia major patients, and cardiac iron overload is the most common reason for death in these transfusion-dependent patients. Hepcidin, a liver-derived peptide hormone, plays a key role in plasma iron levels regulation by controlling two main stages, digestive iron absorption in enterocytes, and iron recycling in macrophages. Although hepcidin is mainly secreted from hepatocytes in the liver, it is also synthesized from mononuclear cells consisting of monocytes and lymphocytes. Binding of this molecule to ferroportin, a specific cellular exporter of iron, leads to degradation of the ligand-receptor complex, which reduces the iron overload by lowering the amounts of iron released into the plasma. Likewise, the same mechanism has been proved to be true for lymphocyte-drived hepcidin. The expression levels of hepcidin mRNA were evaluated using quantitative real time PCR (qRT-PCR) in 50 ß-thalassemia major patients, as well as 25 healthy volunteers as the group of control. There was a significantly positive correlation between the cardiac iron concentration, showed by higher T2 values, and hepcidin levels in the patients (p = 0.028; r = 0.311). However, hepcidin expression levels did not significantly correlate with ferritin and liver iron concentrations. Hepcidin can act as a beneficial marker to determine iron overload degrees, particularly in the heart, in ß-thalassemia major patients and be used as a logical therapeutic agent for treatment of ß-thalassemia disorders.

Absence of FLT3 mutations in Iranian adult T-cell leukemia/lymphoma patients.

Background: Adult T cell leukemia lymphoma (ATLL) is a rare disease, significantly linked to the infection by the human T-cell lymphotropic virus 1(HTLV-1). ATLL is typically preceded by decades of clinical latency during which infected cells accumulate selectable traits leading to a malignant transformation. Amongst all the HTLV-1 infected carriers only about 3-5% will develop ATLL. Despite the intensive attempt to improve the overall survival, ATLL remains one of worse prognosis among the hematologic malignancies. FMS like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) mutations are mutations which are frequent among leukemic patients. We aimed to investigate the frequency of FLT3 mutation status in patients with acute type of ATLL which has not been studied yet. Methods: In this case control study 38 patients with acute type of ATLL were retrospectively analyzed between February 2015 and February 2017. Forty HTLV-1 positive patients were also used as control cases. Genomic DNA was extracted according to phenolchloroform protocol and two restriction fragment length polymorphism (RFLP) PCR reactions were set up to detect FLT3/ ITD and FLT3/TKD mutations. Differences between variables were evaluated by the chi-square test and t test for categorical and continuous variables, respectively. SPSS software v. 15 was used for statistical analysis. All P values were two sided and values less than 0.05 were considered to be significant. Results: No FLT3 mutations were detected in acute type of ATLL patients. So far, not many studies have shown the frequency of FLT3 mutation in ATLL patients Conclusion: Therefore, we conclude that although FLT3 mutations are rather unusual in the acute type of ATLL patients, but other alternative mechanisms associated with ATLL remain to be further investigated. This study was a novel project regarding the analysis of FLT3 mutation in the field of ATLL research.

Quantitative assessment of Wilms tumor 1 expression by real-time quantitative polymerase chain reaction in patients with acute myeloblastic leukemia.

BACKGROUND: The Wilms tumor 1 (WT1) gene is originally defined as a tumor suppressor gene and a transcription factor that overexpressed in leukemic cells. It is highly expressed in more than 80% of acute myeloid leukemia (AML) patients, both in bone marrow (BM) and in peripheral blood (PB), and it is used as a powerful and independent marker of minimal residual disease (MRD); we have determined the expression levels of the WT1 by real-time quantitative polymerase chain reaction (RQ-PCR) in PB and BM in 126 newly diagnosed AML patients. MATERIALS AND METHODS: This study was done in molecular pathology and cancer research center from April 2014 to June 2015, RQ-PCR method was used to determine the WT1 gene expression in BM and/or PB samples from 126 patients of AML, we cloned both WT1 and ABL genes for creating a standard curve, and we calculate copy number of WT1 genes in patients. RESULTS: A total of 126 AML patients consist of 70 males (55.6%) and 56 females (44.4%), with a median age of 26 years; 104 (81%) patients out of 126 show overexpression of WT1 gene. We also concomitant monitoring of fusion transcripts (PML RARa, AML1-ETO, MLL-MLL, CBFb-MYH11, or DEK-CAN) in our patients, the AML1-ETO group showing remarkably low levels of WT1 compared with other fusion transcript and the CBFB-MYH11 showing high levels of WT1. CONCLUSION: We conclude that WT1 expression by RQ-PCR in AML patients may be employed as an independent tool to detect MRD in the majority of normal karyotype AML patients.

Downregulation of the WT1 gene expression via TMPyP4 stabilization of promoter G-quadruplexes in leukemia cells.

The WT1 gene is an important oncogene, and its overexpression is considered as an effective target for anticancer therapy. Regulation of its gene transcription is one way for WT1-targeting drug design. Recently, in silico analysis of some oncogene promoters like WT1 showed some guanine-rich regions with the ability to form G-quadruplex structures. Ligands like 5,10,15,20-tetra(N-methyl-4-pyridyl)-porphine (TMPyP4) have predominant effect on G-quadruplex stabilization. The aim of this study was to understand the effect of TMPyP4 on WT1 gene transcription via stabilization of promoter G-quadruplexes. We examined the formation of new G-quadruplex motifs in WT1 promoter in the presence of TMPyP4. In order to understand the nature of its interaction with WT1 promoter quadruplexes, differential pulse voltammetry (DPV), circular dichroism (CD), polyacrylamide gel electrophoresis, electrophoretic mobility shift assay (EMSA), polymerase chain reaction (PCR) stop assays, and quantitative RT-PCR were performed. According to the results, the WT1 promoter can form stable intramolecular parallel G-quadruplexes. In addition, after 48 and 96 h of incubation, 100 µM TMPyP4 reduced the WT1 transcription to 9 and 0.4 %, respectively, compare to control. We report that ligand-mediated stabilization of G-quadruplexes within the WT1 promoter can silence WT1 expression. This study might offer the basis for the reasonable design and improvement of new porphyrin derivatives as effective anti-leukemia agents for cancer therapy.

Evaluation of BAALC gene expression in normal cytogenetic acute myeloid leukemia patients in north-east of Iran.

Background: Acute myeloid leukemia (AML) is known as one of the most common leukemia among adults. Environmental and different genetic factors affect disease process, prognosis and treatment. Among different genetic factors NPM1, FLT3, MLL and BAALC genes are the most effective on patient's survival rate. The aim of this study was to assess amount of BAALC gene expression in AML patients, and its relation to survival rate. Methods: In this case-control study, from all 94 individuals referred to Ghaem Medical Center during 2012-2015, 47 cases were normal cytogenetic AML and others were healthy individuals that were studied as control group. Real-time PCR method was applied for gene expression evaluation. Other information of patients was extracted from medical documents. SPSS v.21 was used for data processing. Results: Mean age of studied cases was 31.50 years. The most of BAALC gene expression was seen in M1 and M2 subtypes, and the less was in M5. A significant relation was found between amount of gene expression and patient's survival rate. Conclusion: BAALC gene expression was increased significantly in AML cases. BAALC expression had reverse relation with patients' survival rate in North-East of Iran.

Effect of Crocus sativus L. (saffron) on coagulation and anticoagulation systems in healthy volunteers.

Saffron showed some effects on blood coagulation and platelet aggregation in in vitro and in vivo studies. In a clinical trial with a limited number volunteers, saffron tablets influenced on bleeding time. In this study, the effect of saffron on plasma level of fibrinogen, factor VII (as coagulant agent), C and S protein (as anti-coagulant agent), PT and PTT in a larger sample size was evaluated. The study was a double-blind, placebo-controlled study consisting of 1 week treatment with 200 mg and 400 mg saffron tablets. Sixty healthy volunteers (age range 20-50 years) were selected for the study. The volunteers were divided into three groups of 20 each. Group 1 received placebo; Groups 2 and 3 received 200 mg and 400 mg saffron tablets, respectively, for 7 days (1 tablet per day). Before and after 7 days treatment and also 1 month after that, blood samples were taken. The plasma levels of fibrinogen, factor VII, C and S protein, PT and PTT were evaluated. Statistical analysis showed no difference between groups for any of evaluated factors. This study rejected any effect of saffron with dose of 200 and 400 mg for 1 week on coagulant and anticoagulant system.

Effect of selenium on anti-Tg antibody in patients with autoimmune hypothyroidism: A randomized controlled trial.

Background: The current study intends to assess the impact of oral selenium intake on anti-Tg antibody in individuals with autoimmune hypothyroidism. Methods: In this double-blinded randomized controlled trial, two groups of 72 autoimmune hypothyroid patients were randomly assigned; one group received levothyroxine (LT4) and oral selenium and the other group was given placebo with LT4. Anti-Tg antibody, free T4, anti-TPO antibody, and TSH were identified in both groups before the treatment and also 3 months after treatment and analysis of data was done by SPSS software. Results: After the intervention, the average amount of anti-Tg antibody decreased in both of the groups, and this decrease was noticeably greater in the intervention group (P = 0.03). In the intervention group, the TSH level decreased after the intervention (p < 0.05), and the free T4 level increased after the intervention (p < 0.05); the changes in these two variables were statistically significant. Conclusion: Consumption of selenium, compared to placebo, in patients with autoimmune hypothyroidism drastically reduces the level of anti-Tg antibody, and it significantly increases the free T4 level. Also, there is a greater decrease in the level of TSH compared to the control group.

Prognostic significance of ASXL1 mutations in acute myeloid leukemia: A systematic review and meta-analysis.

Background: Although genetic mutations in additional sex-combs-like 1 (ASXL1) are prevalent in acute myeloid leukemia (AML), their exact impact on the AML prognosis remains uncertain. Hence, the present article was carried out to explore the prognostic importance of ASXL1 mutations in AML. Methods: We thoroughly searched electronic scientific databases to find eligible papers. Twenty-seven studies with an overall number of 8,953 participants were selected for the current systematic review. The hazard ratio (HR) and 95% confidence interval (CI) for overall survival (OS), event-free survival (EFS), and relapse-free survival (RFS) were extracted from all studies with multivariate or univariate analysis. Pooled HRs and p-values were also calculated as a part of our work. Results: The pooled HR for OS in multivariable analysis indicated that ASXL1 significantly diminished survival in AML patients (pooled HR: 1.67; 95% CI: 1.342-2.091). Conclusions: ASXL1 mutations may confer a poor prognosis in AML. Hence, they may be regarded as potential prognostic factors. However, more detailed studies with different ASXL1 mutations are suggested to shed light on this issue.

Downregulation of salivary miR-3928 as a potential biomarker in patients with oral squamous cell carcinoma and oral lichen planus.

OBJECTIVES: Recent studies highlighted the role of miR expressed in saliva as reliable diagnostic and prognostic tools in the long-term monitoring of cancer processes such as oral squamous carcinoma (OSCC). Based on a few previous studies, it seems the miR-3928 can be considered a master regulator in carcinogenesis, and it can be therapeutically exploited. This is the first study that compared oral potentially malignant disorder (OLP) and malignant (OSCC) lesions for miR-3928 expression. MATERIALS AND METHODS: In this cross-sectional study, saliva samples from 30 healthy control individuals, 30 patients with erosive/atrophic oral lichen planus, and 31 patients with OSCC were collected. The evaluation of miR-3928 expression by q-PCR and its correlation with clinicopathological indices were analyzed by Shapiro-Wilk, Kruskal-Wallis, Pearson's χ2 , and Mann-Whitney tests. The p-value less than .05 indicated statistically significant results. RESULTS: Based on nonparametric Kruskal-Wallis test results, there was a statistically significant difference between the ages of three study groups (p < .05). This test demonstrated a statistically significant difference between the average of miR-3928 expression in three study groups (p < .05). The result of the χ2  test showed a statistically significant difference in miR-3928 expression between patients with OLP (p = .01) and also patients with OSCC (p < .0001) in comparison to the control group. CONCLUSIONS: The salivary miR-3928 can play a tumor suppressive role in the pathobiology of OSCC, and it is significantly downregulated in patients. According to the potential tumor suppressive role of miR-3928 in the OSCC process, we can consider this microRNA as a biomarker for future early diagnosis, screening, and potential target therapy.

The Emerging Roles of Aldehyde Dehydrogenase in Acute Myeloid Leukemia and Its Therapeutic Potential.

Acute myeloid leukemia (AML) is a malignant disorder characterized by myeloid differentiation arrest and uncontrolled clonal expansion of abnormal myeloid progenitor cells. AML is the most common malignant bone marrow (BM) disease in adults and accounts for approximately 80% of adult leukemia cases. There has been little improvement in the treatment of patients with AML over the past decade. Cytogenetic and morphologic heterogeneity of AML and the difficulty in distinguishing leukemic stem cells (LSCs) from normal hematopoietic stem cells (HSCs) continue to be the major challenges in treating this malignancy. In recent years, intensive efforts have been made to explore novel potential markers for the efficient identification and characterization of leukemic stem cells. Aldehyde dehydrogenase (ALDH) is a potential target molecule that plays crucial roles in leukemic stem cell survival and multidrug resistance, mainly through its involvement in the detoxification of many endogenous and exogenous aldehydes. The selection and isolation of cancer stem cells based on high ALDH activity seem to be a useful approach in many human malignancies, especially leukemia. Moreover, it is worth mentioning that several previous studies have indicated that a high ALDH activity (classified as ALDHbr cells in flow cytometry) can act as an independent prognostic factor in several types of cancer. In the present review, we update and critically discuss the available data regarding the importance of ALDH activity in normal and leukemic stem cells and its potential diagnostic and therapeutic implications.

Evaluation of the expression of LC3-II and BECLIN1 genes of autophagy pathway in patients with hematological malignancies.

Background: Autophagy is a pathway for the degradation of cytoplasmic components, which plays an essential role in various cellular and physiological processes, including cell renewal and survival, and immune responses. While recent studies have shown that they can play a role in cancer treatment, the precise mechanisms of autophagy in leukemogenesis are not fully understood. We have assessed the expression levels of LC3 and BECLIN1 as two crucial autophagy mediators in patients with leukemia. Methods: This cross-sectional study was performed on bone marrow or peripheral blood samples of 61 leukemia patients (24 AML, 20 ALL, and 17 CML) and compared to 18 healthy controls. Real-time PCR was used to quantitate gene expression. SPSS statistics 16.0 and Graph Pad Prism 8.4.2 software were applied for statistical analysis. Results: While BECLIN1 expression was significantly lower in AML, ALL, and CML patients as compared to the control group (p < 0.05), LC3 showed significantly different expression only in the AML patients (P= 0.03). There was no significant correlation between the expression levels of BECLIN1 with LC3 (p> 0.05). Whilst the AML LC3high group had a significantly lower lymphocyte count (P= 0.023), the AML BECLIN1low group had a significantly higher MPV levels (P= 0.044). Furthermore, ALL LC3high group indicated a significantly lower HCT count (P= 0.017). Conclusion: Significant changes in the expression levels of BECLINI and LC3 in hematologic malignancies may indicate a possible role for autophagy in their pathogenesis. However, further studies are warranted to confirm these findings.

Molecular Status of BRAF Mutation in Epithelial Ovarian Cancer: An Analysis of 57 Cases in the Northeast of Iran.

Background & Objective: Epithelial ovarian cancer (EOC) is the most prevalent type of ovarian cancer. Previous studies have elucidated different pathways for the progression of this malignancy. The mutation in the B-Raf proto-oncogene, serine/threonine kinase (BRAF) gene, a member of the MAPK/ERK signaling pathway, plays a role in the development of EOC. The current study aimed to determine the frequency of the BRAF V600E mutation in ovarian serous and mucinous tumors, including borderline and carcinoma subtypes. Methods: A total of 57 formalin-fixed paraffin-embedded samples, including serous borderline tumors (SBTs), low-grade serous carcinomas (LGSCs), high-grade serous carcinomas (HGSCs), mucinous borderline tumors (MBTs), and mucinous carcinomas, and 57 normal ovarian tissues were collected. The BRAF V600E mutation was analyzed using polymerase chain reaction (PCR) and sequencing. Results: While 40% of the SBT harbor BRAF mutation, we found no BRAF mutation in the invasive serous carcinoma (P=0.017). Also, there was only 1 BRAF mutation in MBT and no mutation in mucinous carcinomas. In addition, we found no mutation in the control group. Conclusion: The BRAF mutation is most frequent in borderline tumors but not in invasive serous carcinomas. It seems that 2 different pathways exist for the development of ovarian epithelial neoplasms: one for borderline tumors and the other for high-grade invasive carcinomas. Our study supports this hypothesis. The BRAF mutation is rare in mucinous neoplasms.

Is there any relationship between expressions of minor blood group antigens with HTLV-I infection?

BACKGROUND: The frequency of Human T lymphotropic Virus-1 (HTLV 1) is 2-3% in the general population and 0.7% in blood donors in northeast Iran. It is very important that we recognize the contributing factors in the pathogenesis of this virus. There are many reports that show that susceptibility to some infections is closely linked to the expression of certain blood group antigens. This study was performed to evaluate any association between minor blood group antigens and HTLV-I infection in northeast Iran. METHODS: In this case and control study major and minor blood group antigens were typed by commercial antibodies in 100 HTLV-I infected individuals and 332 healthy blood donors in Mashhad, Iran, from 2009-2010. Blood group antigens were determined by tube method less than 24h after blood collection. Finally, the results of HTLV-I positive subjects and control groups were compared by using SPSS software. RESULTS: The prevalence of Le(a), Le(b), P1, Fy(a), Fy(b), M, N, Jka, Jkb, K and k antigens in case group were 39.0%, 56.0%, 72.0%, 67.0%, 52.0%, 90.0%, 57.0%, 79.0%, 71.0%, 10.0%, 96.0%, respectively and the frequency of these blood group antigens in control group were 38.8%, 55.8%, 66.2%, 72.0%, 58.7%, 87.0%, 56.7%, 79.8%, 63.0%, 10.6%, 97.0%, respectively. We did not find any significant differences between the case and control group for frequency of minor blood group antigens. CONCLUSION: Our study showed minor blood group antigens are not associated with an increased risk of HTLT-1 infection in northeast Iran.

Expression of rhesus blood group antigens in HTLV-i infection in northeast Iran.

BACKGROUND: Human T-cell lymphoma/leukemia virus type 1 (HTLV-1) infection is relatively common in northeast Iran. It is important to understand which factors play a role in the pathogenesis of this virus. Blood group antigens may act as a receptor for various infectious agents. This study was performed to detect any association between Rh blood group antigens and HTLV-1 infection in northeast Iran. METHODS: In this case and control study, Rhesus blood group antigens (D, C, c, E and e) were determined within 24 hours of blood collection by commercial antibodies in 100 HTLV-I infected individuals and 332 healthy blood donors at the Khorasan Blood Transfusion Center, Mashhad, Iran, in 2011. The results of HTLV-I positive subjects and the control group were compared using SPSS software. RESULTS: The frequencies of Rh blood group antigens in the case group were D in 88%, C in 72%, c in 68%, E in 27%, and e in 94%. In the control group the frequencies were D in 91%, C in 75.5%, c in 72.9%, E in 28.6% and e in 98.2%. Chi-square test showed a significant difference between the two groups for the frequency of e antigen (p = 0.03). CONCLUSIONS: Our study showed that e antigen expression is associated with a decreased risk of HTLV-I infection in northeast Iran.

Altered expression of NEAT1 variants and P53, PTEN, and BCL-2 genes in patients with acute myeloid leukemia.

BACKGROUND: Newly discovered evidence showed that long non-coding RNAs (lncRNAs) can play crucial roles in the development of cancer therapies. Nuclear Enriched Abundant Transcripts 1 (NEAT1) is one of the lncRNAs the expression of which changes in different cancers. The role of NEAT1 in apoptosis is discussed in various malignancies. This study aimed to determine the NEAT1 expression and its correlation with P53, PTEN, and BCL-2 genes expression in acute myeloid leukemia (AML) patients. METHOD: In this study, using quantitative real-time polymerase chain reaction (qRT-PCR), we analyzed the expression of NEAT1, P53, PTEN, and BCL-2 genes in 21 AML patients. Moreover, relative quantification analysis was performed by delta-delta CT method (2 -ΔΔCT) method. RESULTS: Our results showed that NEAT1 expression was significantly lower in AML patients compared to healthy controls (P-value < 0.05). While a significant correlation was observed between the expression levels of NEAT1 and PTEN genes in AML patients (P-value < 0.05), there was no correlation between the expression levels of NEAT1 with P53 and BCL-2 (P-value > 0.05). CONCLUSION: According to the results, increased expression of NEAT1 gene may play a role in the apoptosis of AML cells, despite the oncogenic role in most solid tumors.

Detection of TET2 Mutation in Patients with De Novo Acute Myeloid Leukemia: A Mutation Analysis of 51 Iranian Patients.

Acute myeloid leukemia (AML) is a heterogeneous clonal disease that is considered to originate from hematopoietic stem cells, which are characterized by impaired myelopoiesis and blast proliferation. TET oncogene family member 2 (TET2) mutations are frequent in myeloid malignancies and several studies have assessed the clinical importance of TET2 mutations. However, its frequency ratio has not yet been fully clarified. METHOD: Hence, our study was aimed to analyze TET2mut in patients with de-novo AML and their association with clinical, molecular characteristics and Nucleophosmin 1 (NPM1), Fms-like tyrosine kinase 3 (FLT3), CCAAT Enhancer Binding Protein Alpha (CEBPA) and Wilms' tumor protein (WT1) gene expression. Fifty-one Iranian patients were screened by polymerase chain reaction (PCR) and direct sequencing to evaluate TET2 mutations frequency. RESULTS: Out of all patients, 10 mutations in 8 patients (15.6%) were detected and closely associated with higher age and higher hemoglobin levels (p-value <0.05). Although FLT3, NPM1 and CEBPA gene expression did not show any significant correlation with TET2mut, cytogenetically normal acute myeloid leukemia (CN-AML)  patients appear to bear TET2mut more frequently with lower platelet counts. Monocyte-lineages leukemia has seemed to be more linked with TET2mut in these patients. CONCLUSION: Our study suggests the frequency of TET2mut in our study (15.6%) is in line with previous studies and reveals the critical role of TET2 in myeloid transformation, especially in leukemia with monocytic subtypes. 
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