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.

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.

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.

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.

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.

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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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.

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).

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.

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.

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.

BCR-ABL fusion genes and laboratory findings in patients with chronic myeloid leukemia in northeast Iran.

BACKGROUND: A specific chromosomal abnormality, the Philadelphia chromosome (BCR-ABL fusion), is present in all patients with chronic myeloid leukemia (CML). The b2a2 and b3a2 fusion mRNAs encode p210 fusion protein p210 and e1a2 encode p190. The aim of this study was to evaluate the frequency of BCR-ABL fusion transcript variants in Northeast of Iranian CML patients and to compare the laboratory results of our patients. METHODS: This study was conducted in 85 peripheral blood and bone marrow samples of CML patients. Ribonucleic acid (RNA) was extracted by a commercial kit, RT- PCR for identifying BCR-ABL fusions was carried out by using designed primers and the PCR products were electrophoresed in agarose gels. Finally, statistical analysis was performed for variant frequency identification and their comparison was performed. RESULTS: All patients examined were positive for BCR/ABL rearrangement. Fusion of b3a2 was detected in 53 (62.35%) patients, b2a2 in 25 (29.41), e1a2 in 1 (1.17%) and coexpression of b3a2 and e1a2 in 6 (7.05%) patients. There were significant differences between the mean age in patients with b3a2 positive ( 44.07 years) and in b3a2 negative group (50.35 years) however, no significant differences were seen between sex and b2a2 (P=0.61), b3a2 (P=0.79) and e1a2 (P=0.20). CONCLUSIONS: This study showed higher frequency b3a2 than b2a2 and e1a2 transcripts in CML patients in Northeast Iran and there was no association between e1a2 transcripts frequencies and monocytosis in peripheral blood.

Prognostic Value of EVI1 Expression in Pediatric Acute Myeloid Leukemia: A Systematic Review.

Acute myeloid leukemia (AML) as a distortion of blood cells involves the differ entiation of hematopoietic stem cells. Several studies established the irregular over expression of specific genes is a common finding in patients with AML. The ectopic viral integration site-1 (EVI1) gene is a protooncogene subject to alternative splicing, and encodes a zincfinger protein that acts as a transcriptional regulator in early devel opment. Forced overexpression of EVI1 in hematopoietic progenitors later induced a myeloid differentiation block. The current review aimed at determining the prognos tic value of EVI1 expression in patients with AML in the age range of one month to fifteen years. The scientific databases including PubMed, Google Scholar, EMBASE, Scopus, and ISI published up to January 2016 were searched using the conformity keywords and a total of four articles were studied. Three articles declared higher overexpression of EVI1 in patients with mixed-lineage leukemia (MLL) rearrangements. The percentage of overall survival (OS), reported in two articles, decreased in AML patients with high EVI1 expression. A study reported that the relationship between EVI1 expression and OS was negligible in cases with and without EVI1 expression. Another study showed significant differences in event free survival (EFS) and OS in the group of patients with positive MLL-AF9 between EVI1+ and EVI1patients. The current study revealed that high EVI1 expression was not a poor prognostic factor in pediatric patients with AML. And this gene expression was mainly prognostic concomitantly by other factors such as MLL rearrangement, MEL1 expression, and white blood cell (WBC) count.

KRAS Codon 12 and 13 Mutations in Gastric Cancer in the Northeast Iran.

BACKGROUND & OBJECTIVE: KRAS mutations are reported in many types of cancers including pancreas, lung, colon, breast,and gastric (GC). High frequency of KRAS mutation is observed in the pancreas,colon, and lung cancers; they commonly arise in codon 12 and 13 of exon 2. Due to the lack of information about the frequency of KRAS mutations in the Northeast of Iran, the currentstudy aimed at evaluating KRAS frequency in cases with GC in this region. METHODS: A total of120 formalin-fixed, paraffin-embedded blocks of patients with GC were assessed. The assays to detect KRAS in codon 12 and13 were obtained through the peptide nucleic acid (PNA)-clamp. RESULTS: Totally 87 male and 33 female patients were analyzed in the current study. The mean age of the subjects was 55years.The most common tumoral fragment was located on the body with 48 cases (40%) and the less frequent was related to fondues with six cases (5%).Of the 120 GC samples, 16(13.3%) caseshad codon 12 KRAS mutation, and 16.7% had codon 13 mutations. There were no significant relationships between gender,age, and KRAS mutations in the studied specimens. CONCLUSION: In conclusion, the overall frequency of KRAS codon 12 and 13 mutations in GC was 30% in the current study population.Frequency of KRAS codon 12 and 13 mutations hadsignificant correlation with tumors location. Different pathogenic mechanismsare suggested for GC according to tumor location. The current study resultsmay be an important diagnostic tool for physicians managing atrophic gastritis.

Prevalence of MPL (W515K/L) Mutations in Patients with Negative-JAK2 (V617F) Myeloproliferative Neoplasm in North-East of Iran.

BACKGROUND AND OBJECTIVE: Janus kinase 2 (JAK2) and Myeloproliferative Leukemia (MPL) mutations are confirmatory indicators for Myeloproliferative Neoplasm (MPN). The current study was performed to determine the frequency of MPL mutation in MPN patients without JAK2 mutation, in order to assign MPL mutation frequency in North-East of Iran. METHODS: Total of 105 negative JAK2 cases including 5 Myeloproliferative Disorders (MPD), 15 Polycytemia Vera (PV) and 15 Essential Thrombocytosis (ET) who referred to Qaem Medical Center were assigned to this study. ARMS-PCR was carried out for measuring MPL mutations. RESULTS: A significant difference was observed between MPL mutant and non-mutant groups from overview of MPL mutation (P=0.00001). From the total studied population, 14.28% were ET cases and 4.71% of them had splenomegaly. About 66.66% had thrombocytosis and 33.33% of all the individuals had leukocytosis according to WHO criteria, and 4.76% of non-MPL mutant individuals had splenomegaly (P=1).This mutation was reported in 4-6% of ET and PMF individuals. In this research, 4.76 % of studied individuals had MPL (W515L/K) mutation, which were diagnosed with ET. CONCLUSION: Generally, the presence of JAK2 and MPL mutations are the most important criteria for MPN diagnosis. The obtained frequency of MPL mutation was similar to previous studies. Despite the high frequency of JAK2 and Philadelphia abnormality, MPL mutation was rare in myeloprolifrative disorders. Further studies are suggested to investigate its prognostic effects for these diseases.

Cytogenetic Abnormalities with Interphase FISH Method and Clinical Manifestation in Chronic Lymphocytic Leukemia Patients in North-East of Iran.

Background: Chronic lymphocytic leukemia (CLL) is one of the most prevalent adult leukemias. This malignancy is known by lymphocytosis for a duration of more than 3 months. In fact, it is a heterogeneous clinical disease with changeable progression. Chromosomal aberrations are significant parameters to predict result and survival rate and find treatment strategies for each patient. Cytogenetic methods are known as sensitive and relatively new procedures to detect abnormalities in genome. Materials and Methods: In order to identify CLL-related chromosomal abnormalities, 48 CLL patients included 38 Men and 10 Women with mean age of 58.25±36 were enrolled in this case series study.The survey was done at Cancer Molecular Pathology Research Center, Mashhad University of Medical Sciences. Interphase fluorescent in situ hybridization (I-FISH) was done on unstimulated peripheral blood or bone marrow samples, which were cultured in whole medium culture; it was used to detect chromosomal abnormalities such as 11q- , 13q14-, 17p- , 6q- and trisomy 12 in CLL patients. Results: Analysis demonstrated that 45.5% of CLL cases had chromosomal abnormalities; 13.63% haddel 17p, 40.90% had del 13q14 and 9.09% had del 11q. Statistical analysis of data revealed a significant relevancy between age variable and splenomegaly occurrence (P value<0.05). The younger the patients were, the less the splenomegaly occurrence. Conclusion: Laboratory findings were correlated with clinical data.