Serum lipid profiles in acute myocardial infarction patients in Gorgan

Acute myocardial infarction is one of the important reasons of death and unhealthiness in the world. The present study was undertaken to investigate the changes in serum lipids and lipoproteins in patients with acute myocardial infarction. This study was performed in the Biochemistry and Metabolic Disorder Research Center of Gorgan, Golestan province (South East of Caspian Sea), Iran in 2011.The levels of lipid profile were significantly changed in the acute myocardial infarction patients. acute myocardial infarction patients had significantly higher levels of total cholesterol, LDL-cholesterol, VLDL-cholesterol, TG, LDLcholesterol /HDL-cholesterol, total cholesterol /HDL-cholesterol, LDH, CPK and CPK-MB and lower level of HDL-cholesterol, as compared to the control subjects. We found a significant association of lipid profiles with acute myocardial infarction. Changing of dietary and social activity habits of people in this area can help to prevent future atherogenic damaging in AMI patients. Copyright © 2012, Scientific Publisher of India

Polymorphisms of the methylene tetrahydrofolate reductase and susceptibility to acute lymphoblastic leukemia in children

Background: Correlation between epigenetic factors and their effects on hematopoietic cells has led to a study of 2 common functional polymorphisms (C677T and A1298C) of 5,10-methylene tetrahydrofolate reductase (MTHFR) enzyme. The aim of this study was to assess the individual and/or combined roles of these 2 polymorphisms in pediatric acute lymphoblastic leukemia (ALL). Methods: Using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analyses, we studied the frequencies of the C677T and A1298C MTHFR genotypes in 103 pediatric ALL patients and 160 age-sex matched controls. We calculated the odds ratio (OR) of MTHFR genotypes to determine if 1 or both of these polymorphisms may be associated with childhood ALL. Results: The T allele frequency for MTHFR 677C>T was 22.2 and 18.45 in controls and cases, respectively. The C allele frequency for MTHFR 1298 A>C was 40.65 and 40.72 in controls and cases, respectively. The OR for MTHFR 677CT was 1.08 (95CI 0.58-1.95) and OR for MTHFR 677TT was 0.25 (95CI 0.05-10.24). The OR for MTHFR 1298 AC was 0.57 (0.95 CI 0.57-1.95) and for MTHFR CC was 0.96 (0.95 CI 0.37-2.45). The OR for the combined heterozygous status (677CT and 1298AC) was 1.08 (95 CI 0.41-2.82). Conclusion: Our findings suggest that the MTHFR C677T and A1298C gene variants lack a major influence on the susceptibility for pediatric ALL. Another result was that the C allele frequency for MTHFR 1298 A>C was significantly higher than those reported for most Asian and European populations. The C677T prevalence seems to be similar to those reported in most Asian populations. © 2011 by The American Society for Clinical Pathology

Detection of nucleophosmin and FMS-like tyrosine kinase-3 gene mutations in acute myeloid leukemia

BACKGROUND AND OBJECTIVES: Nucleophosmin gene mutations are frequently reported in acute myeloid leukemia (AML) patients with normal karyotype, which is also frequently associated with internal tandem duplication mutations in the FMS-like tyrosine kinase-3 gene. We sought to detect the nucleophosmin and FMS-like tyrosine kinase-3 (FLT3) internal tandem duplication (ITD) mutations among Iranian patients with AML and to assess the relationship between these mutations and the subtypes of the disease. DESIGN AND SETTING: Cross-sectional study of patients referred during 2007 through 2009. PATIENTS AND METHODS: Bone marrow and peripheral blood samples of 131 AML patients were randomly collected at the time of diagnosis and prior to treatment and the DNA extracted. After amplifying the nucleophosmin and FLT3 gene regions, positive cases were screened by conformation-sensitive gel electrophoresis and agarose gel electrophoresis techniques. RESULTS: Of 131 patients, 23 (17.5) (0.95 CI=0.107-0.244) had nucleophosmin gene mutations. The highest frequency of such mutations was found among the subtypes of M4 (30.4), M3 (21.7) and M5 (17.4). There was a high frequency of these mutations in the M3 subtype as well as a high frequency of allele D in all subtypes. Also, 21 (16.0) samples (0.95 CI=0.092-0.229) had FLT3/ITD mutation, of which 8 samples had mutant nucleophosmin (8 of 23, 35), and another 13 samples had wild-type nucleophosmin gene (13 of 108, 12). There was a high degree of association between the occurrence of nucleophosmin and FLT3/ITD mutations (P=.012). CONCLUSION: Our data showed a high frequency of NPM1 mutations in the monocytic subtypes of AML, as well as a high degree of association between the occurrence of NPM1 and FLT3/ITD mutations

A study on the antitumoral and differentiation effects of peganum harmala derivatives in combination with ATRA on leukaemic cells

Plant derived agents may exert a new approach to the treatment of leukaemia. The present study was an evaluation of proliferation, cytotoxicity and differentiation of harmine and harmaline on HL60 cells, alone or in combination with ATRA and G-CSF. Counting of cells, viability, MTT assay, morphology, NBT reduction and flow cytometry analysis were performed using CD11b and CD 14 monoclonal antibodies. The data showed that harmine and harmaline reduced proliferation in dose and time dependent manner. Optimal antiproliferative concentration of these agents was chosen. However, both agents in higher doses were cytotoxic. Combination of ATRA, G-CSF and each agent alone, particularly harmaline in optimal dose, resulted in partially additive decrease in cell proliferation. Cells treated with both harmaline and ATRA demonstrated some morphological changes and NBT positivity, but the extent of changes observed following treatment with harmaline was less than ATRA. Flow cytometric analysis showed that ATRA induced a neutrophilic differentiation, while harmaline led to a predominantly monocytic differentiation. Combination of harmine and harmaline with ATRA and G-CSF did not change the extent of differentiation, and the cells differentiated into the neutrophilic lineage. This shows that the direction of differentiation is dominantly determined by ATRA. These preliminary data implies a new approach in treatment of leukemia

Frequency of CYP1A1*2C polymorphism in patients with leukemia in the Iranian population

Background: CYP1A1, a member of the cytochrome P450 (CYP) enzymes, plays a very important role in metabolizing carcinogens. The aim of this case-control study was to detect the frequency of CYP1A1*2C polymorphism in Iranian leukemic patients and determine the role of this allele's variants, if any, as a risk factor for developing leukemia. Methods: Thirty-nine patients with chronic myeloid leukemia (CML), 105 with acute myeloid leukemia (AML), 95 healthy volunteers as the adult control group, 85 children with acute lymphoblastic leukemia (ALL), and 94 healthy children as the children control group were studied. Genomic DNA was assayed for restriction fragment length polymorphism (RFLP) in the CYP1A1*2C loci by amplification followed by digestion with BsrDI. Results: The frequencies of AA genotype (wild) were 82.05, 62.85, 84.70, 85.10, and 80 in CML, AML, ALL, the children control group, and the adult control group, respectively. The frequencies of AG genotype (heterogeneous) were 17.95, 36.20, 15.30, 14.90, and 18.95 in CML, AML, ALL, the children control group, and the adult control group, respectively. The frequencies of GG genotype (mutant) were 0.95 and 1.05 in AML and the adult control groups respectively; whereas, it was not observed in CML, ALL, or the children control group. Logistic regression analysis showed a significant correlation between the CYP1A1*2C polymorphism AG and AML patients (OR=2.4, 95 CI=1.3-4.7, P>0.05). Conclusion: A higher frequency of CYP1A1*2C, observed in AML patients, compared with the adult control group indicates an increased risk for AML in individuals carrying the heterozygote allele CYP1A1*2C. However, the results did not show any association between CYP1A1*2C genotypes and risk of ALL or CML. © 2011 by The American Society for Clinical Pathology

miR-101 sensitizes K562 cell line to imatinib through Jak2 downregulation and inhibition of NF-κB target genes

Imatinib mesylate (IM) is a frontline treatment in the early chronic phase of chronic myeloid leukemia (CML). However, intrinsic and acquired resistance against this drug has been defined and this issue has become a problem and a challenge in CML treatment. According to new findings, the inhibition of Janus kinase 2 (Jak2) in Bcr�Abl+ cells can promote apoptosis in IM-resistant cells. microRNAs (miRNAs) regulate the gene expression by targeting the messenger RNA (mRNA) for degradation. Recently, a growing body of evidence has implicated that dysregulation of miRNAs is associated with cancer initiation and development. In this report, we proposed that miRNA-101 targets Jak2 mRNA and regulates its expression and induces K562 leukemia cell apoptosis. Here, we transduced the K562 cell line with a miR-101-overexpressing vector and evaluated the Jak2 mRNA level. Our results showed that miR-101 overexpression in Bcr�Abl+ cells reduced the Jak2 mRNA level. Moreover, imatinib treatment and miR-101 upregulation led to miR-23a overexpression, which has putative binding site(s) on 3�-untranslated regions (3�-UTRs) of STAT5, CCND1, and Bcl-2 genes. Our results also indicated that miR-101 overexpression inhibited cell proliferation indicated by the MTT assay and promoted apoptosis detected via flow cytometry. Importantly, mRNA expression of NF-kappa B-regulated anti-apoptotic (Bcl-2, Bcl-xl, MCL-1, XIAP, and survivin) and proliferative (c-Myc and CCND1) genes was decreased. These findings suggest that miR-101 acts as a tumor suppressor by downregulating Jak2 expression and sensitizing K562 cells to imatinib. Therefore, restoration of miR-101 may be a therapeutic approach for CML treatment. © 2016, International Society of Oncology and BioMarkers (ISOBM)

Epigenetic changes in FOXO3 and CHEK2 genes and their correlation with clinicopathological findings in myelodysplastic syndromes

Objectives/background: Myelodysplastic syndromes (MDSs) are a heterogeneous disease in terms of clinical course and response to therapy. Epigenetic changes are the primary mechanism of MDS pathogenesis. FOXO3 and CHEK2 genes play significant roles in normal cellular mechanisms and are also known as tumor suppressor genes. We aimed to clarify the correlation of epigenetic changes in these genes with clinicopathologic findings in MDS. Methods: A total of 54 newly diagnosed MDS patients referred to Shariati and Firouzgar Hospitals (Tehran, Iran) were included in the study from 2013 to 2015, comprising the following cases: 26 with refractory cytopenia with unilineage dysplasia, 10 with refractory cytopenia with multilineage dysplasia, four refractory anemia with excess blasts-1 (RAEB-1), 11 refractory anemia with excess blasts-2 (RAEB-2), and three MDS associated with isolated deletion (5q-). Risk groups were determined according to the Revised International Prognostic Scoring System (IPSS-R). The methylation status of CHEK2 and FOXO3 promoters were determined by methylation-sensitive high-resolution melting analysis of sodium bisulfite-converted DNA. Expressions of CHEK2, FOXO3, and GAPDH were measured by quantitative real-time polymerase chain reaction and fold changes were calculated using the ��CT method. Results: Statistical analysis revealed no promoter methylation of CHEK2 and FOXO3 in healthy control specimens. FOXO3 promoter methylation was associated with high-risk World Health Organization subgroups (p = .017), high-risk IPSS-R (p = .007), high-risk cytogenetics (p = .045), and more than 5 blasts in bone marrow (p = .001). CHEK2 promoter methylation was correlated with more than 5 blasts in bone marrow (p = .009). Conclusions: Promoter methylation of CHEK2 and especially FOXO3 is associated with adverse clinicopathological findings and disease progression in MDS. © 2020 King Faisal Specialist Hospital & Research Centr

Arsenic trioxide selectivity induces apoptosis within the leukemic cells of APL patients with t (15;16) translocation

Acute Promyelocytic Leukemia is a sub type of acute myelogenous leukemia that occurs in about 10-15 of patients with AML. Arsenic trioxide (ATO) as a single agent can induce remission in relapsed and newly diagnosed patients. Among all the arsenic putative functions responsible for these clinical responses, induction of differentiation and apoptosis with low and high doses are the most prominent mechanisms respectively. To evaluate the in vivo apoptotic pattern in leukemic cells of APL patients a single-laser, triple-color flowcytometric method was used, to detect leukemic apoptotic cells in a heterogeneous population of bone marrow samples with Annexin V and 7AAD. A substantial apoptosis which was selectively induced in Promyelocytic cells was detected during the early and middle stages of treatment. © 2006 Asian Network for Scientific Information

The Founder Effect? -FXIII Deficiency in Southeast Iran: A Molecular Study Report

Background: Congenital factor XIII (FXIII) deficiency is an extremely rare bleeding disorder (RBD) with different clinical coagulation disorders and great impacts on the perioperative patient outcome. Its prevalence in Southeast Iran is approximately 4,000 times higher than the worldwide prevalence, with Trp187Arg (c.559T> C as the only causative mutation of FXIIID there. We investigated the founder effect of rs1742924, rs4960181, rs3778360 and rs4142290 using haplotype analysis to define the genetic phenomenon in this geographic region. Materials and Methods: In a case-control study, 10 patients with FXIIID and 10 healthy individuals were assessed. Initially, Trp187Arg (c.559T> C) mutation was assessed in all study populations using a PCR-RFLP technique, then haplotype analysis was performed by assessing rs1742924, rs4960181, rs3778360 and rs4142290 polymorphisms. Data were analyzed using a two-proportion z-test. Results: All patients were homozygote for Trp187Arg (c.559T>C), and this mutation was not observed in any form of homozygote or heterozygote in the control group. Polymorphisms in rs1742924, rs4960181, and rs377836 were homozygote (TT, GG, GG, respectively) and T, G, and G alleles distribution in cases and controls with significant difference (P<0.001, P<0.001, and P=0.01 respectively). Rs4142290 polymorphism showed no significant difference between patients and controls (P=0.3). Two types of haplotypes were observed in the case group, and haplotype number 1* was observed among 90% of them, while not observed in the control group. Conclusion: It seems that founder effectors of haplotype number *1 have more antiquity versus other haplotypes, and probably founder effect is responsible for this high prevalence of FXIIID in the southeast of Iran

Methylenetetrahydrofolate reductase gene polymorphisms and risk of myeloid leukemia

Objective: 5,10-Methylenetetrahydrofolate reductase (MTHFR) involved in folate metabolism has an important role in a cell because folate availability is critical for DNA integrity. This research aims to evaluate, in a case-controlled study, if the polymorphisms in MTHFR gene contribute to altering susceptibility to leukemias of acute myeloid leukemia (AML) and chronic myeloid leukemia (CML). Materials and Methods: Thirty-eight CML patients and 106 AML patients were diagnosed based on detection of BCR-ABL fusion gene by reverse transcription polymerase chain reaction (RT-PCR) and immunophenotyping by flow cytometry. A control group containing 97 healthy, age- and sex-matched individuals participated in this study. Methylenetetrahydrofolate reductase C677T and A1298C polymorphisms in the patient and control groups were evaluated by using the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) technique. We assessed the relationship between the MTHFR genotype and the risk of hematologic malignancies by calculating the odds ratio (OR) with a 95 confidence interval (CI) using conditional logistic regression. Results: The frequencies of CT and TT genotypes (of 677 allele) and AC and CC genotypes (of 1298 allele) among AML patients did not show a statistically significant difference when compared with those of the controls. Also, among CML patients, the frequencies of above stated genotypes did not show statistically significant differences compared with those of the controls. Conclusions: The data indicate that because of no statistical difference in the frequencies of MTHFR gene polymorphisms (C677T and A1298C) in the patient and control groups, these polymorphisms do not contribute to an inherited genetic susceptibility of AML and CML