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.

Challenges of expressing recombinant human tissue factor as a secreted protein in Pichia pastoris.

Tissue factor (TF) is the core reagent in the prothrombin time (PT) assay. In this study, expression and α-factor mediated secretion of three forms of tissue factor (full-length TF (Full-TF), extracellular plus transmembrane domain (TED-TF), and only extracellular domain (ED-TF) were investigated in Pichia pastoris. The amino acid sequence of TF was obtained from the UniProt database, back-translated and codon-optimized for expression in Pichia pastoris. The Full-TF sequence was synthesized but the ED-TF, TED-TF coding fragments were extracted from the Full-TF by PCR. All the coding sequences were cloned into pPICZαA vector in-frame with the α-factor; and electroporated into KM71H. The culture supernatants and the cell lysates were analyzed using SDS-PAGE, dot-blotting, and Western-blotting for expression of TF. The Full-TF and TED-TF expression vector pPICZαA were successfully inserted into the KM71H, but the product was not detected in the SDS-PAGE analysis of the culture supernatant. However, ED-TF expression and secretion was verified by SDS-PAGE, dot blotting, and Western blotting. It seems that the TM domain in the Full-TF and TED-TF have an important role in impairing α-factor-mediated secretion of TF. Therefore, further investigation is necessary to overcome challenges of expressing Full-TF as a heterologous protein in P. pastoris.

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.

Frequency of Kell and Rh alloantibodies in Iranian Thalassemia Patients in Khorasan Razavi Province, Iran.

Background: Thalassemia is an inherited disease with anemia and hemolysis. Blood transfusion is a routine treatment for thalassemia patients; alloimmunization is one of the complications of blood transfusion, which is very serious for these patients, especially girls and young women. Materials and Methods: In this cross-sectional study, 446 thalassemia patients were examined. Demographic information of patients was extracted and recorded. The phenotype of ABO, Rh, and Kell antigens (tube method) with antisera from IMMUNDIANOSTICA Company (Germany) and the frequency of alloantibodies were determined. Results: 55.8% of the studied individuals were male, and 44.2% were female. Mean age of the studied patients was 19.94±10.63. The alloantibodies were detected in 7.5% of cell-pack receivers. The most prevalent phenotype of the ABO system was the O blood group (37.4%), and the most abundant antigen of the Rh group was 'e', which was found in 99.8% of the studied population. The most common alloantibody detected was Anti K (38.2%); concerning kell phenotype, (K_k+) and (K+k+) were found in 99.3% and 0.7% of patients, respectively. The frequency of Anti-D, Anti-C, Anti-c, and Anti-E was 23.5%, 14.7%, 2.9%, and 14.7%, respectively. Conclusion: According to the results of this paper, finding the compatible packed cells in terms of Kell and Rh systems antigens in addition to the ABO blood group is recommended to decrease the rate of alloantibodies in thalassemia patients.

Auraptene-induced cytotoxic effects in acute myeloid leukemia cell lines.

Acute myeloid leukemia is one of the most commonly identified hematological malignancies with poor prognosis. This research was planned to identify the cytotoxic effects of Auraptene on HL60 and U937 cell lines. The cytotoxic effects of Auraptene were measured by AlamarBlue assay (Resazurin) after 24- and 48-h treatments with different doses of Auraptene. The inductive effects of Auraptene on cellular oxidative stress were investigated by determining cellular ROS levels. The cell cycle progression and cell apoptosis were also evaluated by flow cytometry method. Our findings revealed that Auraptene decreased HL60 and U937 cellular proliferation by downregulation of Cyclin D1. Auraptene also induces cellular oxidative stress by upregulation of cellular ROS levels. Auraptene induces cell cycle arrest the early and late phases of apoptosis by upregulation of Bax and p53 proteins. Our data suggest that the anti-tumor function of Auraptene can be mediated by promoting apoptosis and cell cycle arrest and inducing cellular oxidative stress in HL60 and U937 cell lines. These results support that Auraptene may be used as a potent anti-tumor agent against hematologic malignancies in the further studies.

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.

Role of the Lewis and ABO Blood Group Antigens in Helicobacter pylori Infection.

BACKGROUND: Helicobacter pylori infection is a major risk factor for chronic gastritis and gastric cancer. Some findings show increased frequencies of these diseases in individuals with type O blood and in secretors (expressing Le(b) antigen), but other studies have not found any relationship between blood groups and this infection. Given that H. pylori infection and gastric cancer are common in Iran, the assessment of the pathogenesis of this infection in relation to these blood groups could be valuable. METHODS: In a cross-sectional study, we determined the ABO and Lewis blood groups of participants using the tube method and evaluated the level of anti-H. pylori immunoglobulin G using an enzyme-linked immunosorbent assay. This study included 171 Iranian blood donors from Mashhad, Iran, during 2010. The significance of the differences in the frequencies of the Lewis and ABO phenotypes between individuals infected with and without H. Pylori infection were tested using the Chi-square test. A P-value < 0.05 was considered significant. RESULTS: H. pylori infection was found in 76.6% of the study subjects (n = 131). The most common ABO blood group was O (33.9%), and the most common Lewis blood group was Le(a-b+) (54.7%). The frequencies of the ABO, Lewis, and secretion phenotypes were not significantly different between the infected and uninfected subjects. CONCLUSION: We did not find any significant relationship between the Lewis, ABO, and secretion phenotypes and H. pylori infection.

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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Evaluation of FLT3-ITD Mutations and MDR1 Gene Expression in AML Patients.

Background & Objective: Acute myeloid leukemia (AML) is a hematopoietic malignancy caused by genetic abnormalities. Currently, molecular and genetic factors are routinely used as diagnostic and prognostic markers. FLT-3 is one of the most known diagnostic factors in AML. MDR1 gene belongs to the ATP binding cassette family; it is known as one of the chemotherapy-resistant causes of AML. We aimed to study FLT-3ITD mutations and their association with MDR1 gene expression in AML individuals. Methods: For investigation, 80 AML individuals and 20 healthy controls were selected. This study was done in the Cancer molecular Pathology Research Center of Mashhad University of Medical Sciences (MUMS), Iran during 2017-2019. FLT3-ITD mutation was assessed by polymerase chain reaction (PCR); Real-time quantitative PCR was performed to measure the amount of MDR1 gene expression. Bone marrow and blood smears of patients were evaluated in terms of morphology. SPSS 16.0 was used for data analysis. Results: FLT3-ITD mutation and MDR1 overexpression were found in 18.8% and 23.8% of AML patients, respectively. Statistical analysis did not show any relationship or association between these two markers. Cuplike morphology was observed in blast cells in 21.25% of AML cases, which was associated with the presence of FLT3-ITD mutation. Conclusion: FLT-3 and MDR1 function independently. Survival studies to determine the exact role of MDR1 overexpression in drug resistance issues would be suggested.

Blood group antigens frequencies in the northeast of Iran.

BACKGROUND: Identification of blood group antigen frequencies in a population has various benefits in transfusion medicine. Most data in the literature include frequencies of these antigens in European and American countries. In this study for the first time we have reported frequencies of these antigens in the northeast of Iran. MATERIALS AND METHODS: Blood group antigens were characterized in the 522 blood donors in Mashhad, Iran. The following antigens including ABO, Rh (D, C, E, c, e), MNSs (M, N, S, s), Lutheran (Lu(a), Lu(b)), P (P, P(1)), Kell (K, k, Kp(a), Kp(b)), Lewis (Le(a), Le(b)), Duffy (Fy(a), Fy(b)) and Kidd (Jk(a), Jk(b)) were typed and phenotypes frequencies were expressed as a percentage. RESULTS: In the ABO blood group, the most common phenotype was O (33.9%) followed by A, B and AB. In the Rh blood group, the most common antigen was e (97.9%) and R(1)r (31.8%) being the most common phenotype. The most common phenotypes for MNSs, P, Lu and Kell blood group were M+N+, S-s+, P(1), Lu (a-b+), K-k+ and Kp (a-b+). A very rare phenotype of Lu (a-b-) was also observed in 2.7% of cases. We found rare phenotypes of Le (a+b+) and Fy (a-b-) in 7.9% and 3.4% of subjects, respectively. CONCLUSION: We determined some differences in phenotype frequencies of blood group compared with other studies. We found higher frequencies of B blood group and also more frequencies of some rare phenotypes, Lu (a-b-), Le (a+b+) and Fy (a-b-).

The Frequency and Risk Factors of Human T-cell Lymphotropic Virus Type I among Blood Donors in Khorasan-e Razavi, Iran, from 2002 to 2013.

INTRODUCTION: Human T-cell lymphotropic virus (HTLV-I) is the causative agent for adult T-cell lymphoma/leukemia (ATLL) and HTLV-I-associated myelopathy/tropical spastic paraparesis. The virus is endemic in the parts of Iran. This study is conducted to determine the trends in the frequency of HTLV-I in Mashhad, a city in Khorasan-e Razavi province, Iran, over 11 years. MATERIALS AND METHODS: Blood bank records of blood donors positive for HTLV-I were collected from different blood banks across Mashhad between 2002 and 2013. Obtained data were first entered into paper versions and then were analyzed by SPSS version 11.5. HTLV-I antibody was firstly measured by enzyme-linked immunosorbent assay (ELISA) method and later confirmed by the Western Blot (WB). RESULTS: During the study period, 983,000 donors were examined by ELISA and WB, among whom 2921 cases (0.297%) were positive HTLV-I carriers. The highest and lowest frequency of carriers was 0.451% and 0.098%, respectively. The most significant factor was related to marital status (85.2%) and the smallest significant factor was associated with the history of acupuncture (0.3%) according to the different risk factors. CONCLUSION: The frequency of HTLV-I carriers among blood donors was significantly decreased in this period. Screening of blood donors for HTLV-I infection played a significant role in this reduction.

Synergy between parthenolide and arsenic trioxide in adult T-cell leukemia/lymphoma cells in vitro.

OBJECTIVES: Adult T-cell leukemia/lymphoma (ATLL) is an aggressive lymphoid malignancy with low survival rate and distinct geographical distribution. In search for novel chemotherapeutics against ATLL, we investigated the combinatorial effects of parthenolide, a sesquiterpene lactone with valuable pharmaceutical activities, and arsenic trioxide (ATO) in vitro. MATERIALS AND METHODS: MT2 cells, an ATLL cell line, were treated with increasing concentrations of parthenolide (1.25, 2.5, and 5 µg/ml) and ATO (2, 4, 8, and 16 µM) to determine their IC50. Then, cells were treated with a combination of sub-IC50 concentrations of parthenolide (1 µg/ml) and ATO (2 µM) for 72 hr. Cell viability and cell cycle changes were assessed by Alamar blue and PI staining, respectively. To understand the mechanisms responsible for observed effects, expression of CD44, NF-κB (REL-A), BMI-1, and C-MYC were investigated by real-time PCR. RESULTS: Assessment of cell viability indicated that parthenolide significantly increased the toxicity of ATO, as confirmed by accumulation of MT2 cells in the sub G1 phase of the cell cycle. Moreover, molecular analysis revealed significant down-regulation of CD44, NF-κB (REL-A), BMI-1, and C-MYC upon combinatorial administration of parthenolide and ATO in comparison with relevant controls. CONCLUSION: Taken together, present results showed that parthenolide significantly enhanced the toxicity of ATO in MT2 cells. Therefore, the future possible clinical impact of our study could be combinatorial use of parthenolide and ATO as a novel and more effective approach for ATLL.

The Survival of Patients with t(15;17)(q22;q12) Positive Acute Promyelocytic Leukemia: A Study in North-East of Iran.

BACKGROUND & OBJECTIVE: Acute promyelocytic leukemia (APL) with t(15;17)(q22;q12) is a relatively common subtype of acute myeloid leukemia (AML). Here, our objective was to ascertain the survival of patients with this leukemia in north-east of Iran. METHODS: Survival rates of 42 APL patients with t(15;17)(q22;q12) were assessed. Clinical information was obtained from archived medical records. Statistical analysis was performed by SPSS 18 software using log-ranked test and Kaplan Maier survival analysis. RESULTS: Females and males comprised 49% and 51%, respectively. The mean age at diagnosis was 34.3 ± 14.1 years old. During the study period, 17 demises occurred in males, while this number was 7 in females. The mean survival of patients (month) was 23.22 ± 3.57 (95% CI: 16.21 ± 30.2). The five-year survival rate obtained 30%. Regarding demographic and clinical features, the highest rates of 5-year survival were recorded in patients with 20-35 years old (47.6%), males (51%), white blood cell count <10 × 10 9 /l (48%), and platelet count >140 × 10 9 /l (100%). CONCLUSION: Younger age, lower WBC count and higher platelet count were significantly associated with longer survival in AML patients with t(15;17)(q22; q12).

Prognostic significance of SF3B1 mutations in patients with myelodysplastic syndromes: A meta-analysis.

Splicing factor 3B subunit 1 (SF3B1) is a complex takes part in intron splicing of pre-mRNA and mutations within it have been reported frequently in myeloid malignancies including myelodysplastic syndromes (MDS). However, its prognostic value has been controversial. Hence, we aimed this meta-analysis to investigate the prognostic effect of SF3B1 mutations in patients with MDS. Several electronic databases were searched in of EMBASE, PubMed, the Cochrane Library and Web of Science (published up to November 2017) to obtain eligible studies. The pooled Hazard Ratio (HRs) and 95% confidence interval (CI) for overall survival (OS) and leukemia-free survival (LFS) as the primary and secondary endpoint, respectively, were chosen and extracted to determine the prognostic impact of SF3B1 mutations and to compare SF3B1 mutations to those with wild-type. Nine cohort studies with a total of 2259 patients were obtained, and the pooled HRs for OS was 0.93 (95% CI: 0.56-1.52, p-value = 0.78) and revealed no significant effect on overall survival of MDS patients by random effect models. Our meta-analysis suggested that SF3B1 has no impact on OS of patients with MDS, however, an adequately designed prospective study with a large number of patients with different type of SF3B1 mutations is needed to confirm these results. Additionally, Begg's and Egger's tests did not show any publication bias.

Changes in Cytokeratin 18 during Neoadjuvant Chemotherapy of Breast Cancer: A Prospective Study.

BACKGROUND & OBJECTIVE: Prediction of response to neoadjuvant treatment is an important part of treatment of patients with breast cancer. This study aimed to assess changes in serum levels of Cytokeratin 18 during neoadjuvant chemotherapy in patients with locally advanced breast cancer and its association with neoadjuvant treatments. METHODS: This research was performed on newly diagnosed breast cancer patients referred to Omid Radiotherapy Center and radiotherapy and oncology departments of Emam Reza and Ghaem hospitals, in Mashhad, Iran. Serum levels of M30 and M65 fragments of Cytokeratin 18 were measured before and 24 hours after the first course of neoadjuvant chemotherapy. Changes in serum levels of Cytokeratin 18 and its fragments and their correlation with pathologic response were analyzed. RESULTS: Pre- and post-chemotherapy levels of M30 were respectively 223.9±18.94 and 250.7±23.92 U/L (P=0.24). For M65, these levels were respectively 301.5±313.9 and 330.2±352.2 U/L (P=0.1). Changes in M30 level during chemotherapy in patients with and without pathologic complete response were -20±92.69 and 43.1±106.5, respectively (P=0.1). For M65, these changes were respectively -247±55 and 76±240 (P=0.1). Baseline levels of M30 and M65 had no relation with menopausal status, tumor grade, hormone receptor status, Ki67 expression, molecular subtype, and stage. CONCLUSION: Our findings showed statistically insignificant changes in the level of Caspase-cleaved- (M30) and uncleaved- (M65) cytokeratin 18 fragments (apoptotic and necrotic indicators, respectively) during neoadjuvant chemotherapy in patients with breast cancer. There was no notable relationship between tumor-related factors and either baseline levels or serum changes of CK18 fragments. Also, there was no correlation between M30/M65 level and pathologic response to neoadjuvant chemotherapy.

Assessment of T helper 17-associated cytokines in thromboangiitis obliterans.

BACKGROUND: The management of thromboangiitis obliterans (TAO) remains a medical challenge because of its unknown etiology. It is also not known whether it is a systemic or localized disease or a type of autoimmune vasculitis. METHODS: In this study, we evaluated the serum level of IL-17 and IL-23 which increase in both systemic inflammation and autoimmunity, in 60 TAO patients and 30 age- and smoking habit-matched controls. Also, IL-22, which has reported high level during infection but not in autoimmunity, was evaluated. RESULTS: The serum levels of IL-17, IL-22 and IL-23 were significantly higher in the TAO patients in comparison with the controls (P<0.001). Notably, the serum levels of IL-17, IL-22 and IL-23 were highest in the patients with the chief complaint of chronic ulcer and lowest in the patients with gangrene (P<0.05). Also, the serum level of IL-22 was significantly higher in the anemic patients in comparison with the non-anemic patients (P=0.03). CONCLUSION: Owing to our findings, TAO appears more likely to be a systemic disorder rather than a localized vasculopathy. Therefore, treatment protocols based on systemic treatment of TAO patients may be more helpful than localized treatment, such as bypass surgery and endovascular procedures. Also, according to our findings regarding the high level of IL-22, the trigger of TAO development may be an infectious pathogen. However, additional research is highly recommended to investigate whether TAO is an infectious disease or an infectious-induced autoimmunity.

Comparison of miRNA Profiles of Cord Blood Stem Cells in Identical and Fraternal Twins.

OBJECTIVE: The role of epigenetic in regulating of the gene expression profile the embryo has been documented. MicroRNAs (miRNAs) are one of these epigenetic mechanisms. Twins are valuable models in determining the relative contributions of genetics and the environment. In this study, we compared differences in the expression levels of 44 miRNAs in hematopoietic stem cells (HSCs) of identical twins to that of fraternal twins as a controls. MATERIALS AND METHODS: In this experimental study, CD133+ HSCs were isolated from cord blood of identical and fraternal twins via magnetic-activated cell sorting (MACS). Variation in of gene expression levels of 44 miRNAs were evaluated using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). RESULTS: Significant differences in expression were observed in both fraternal and identical twins to varying degrees, but variations alteration in expression of the miRNAs were higher in fraternal twins. CONCLUSION: Identical twins had a positive correlation in miRNA expression, while the correlation was not statistically significant in fraternal twins. Altogether, more differences in miRNA expression level in fraternal twins can be attributed to the both genetics and the intrauterine environment. The contribution of the intrauterine environment and genetics to miRNAs expression in HSCs was estimated 8 and 92%, respectively. By comparing of miRNA expression in identical and fraternal twins and identification of their target genes and biological pathways, it could be possible to estimate the effects of genetics and the environment on a number of biological pathways.