Publications by authors named "Behzad Poopak"

17 Publications

  • Page 1 of 1

ABL Kinase Domain Mutations in Iranian Chronic Myeloid Leukemia Patients with Resistance to Tyrosine Kinase Inhibitors.

Lab Med 2020 Aug 21. Epub 2020 Aug 21.

Department of Hematology, Tehran Medical Sciences Branch, Islamic Azad University, Tehran, IR Iran.

Objective: Tyrosine kinase inhibitors (TKIs) are considered standard first-line treatment in patients with chronic myeloid leukemia. Because ABL kinase domain mutations are the most common causes of treatment resistance, their prevalence and assessment during treatment may predict subsequent response to therapy.

Methods: The molecular response in Bcr-Abl1IS was tested via quantitative real-time polymerase chain reaction. We used the direct sequencing technique to discover the mutations in the ABL kinase domain. The IRIS trial established a standard baseline for measurement - (100% BCR-ABL1 on the 'international scale') and a major molecular response (good response to therapy) was defined as a 3-log reduction in the amount of BCR-ABL1 - 0.1% BCR-ABL1 on the international scale.

Results: We observed 11 different mutations in 13 patients, including E255K, which had the highest mutation rate. A lack of hematologic response was found in 22 patients, who showed a significantly higher incidence of mutations.

Conclusion: Detection of kinase domain mutations is a reliable method for choosing the best treatment strategy based on patients' conditions, avoiding ineffective treatments, and running high-cost protocols in patients with acquired resistance to TKIs.
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http://dx.doi.org/10.1093/labmed/lmaa052DOI Listing
August 2020

Adoptive Treg cell-based immunotherapy: Frontier therapeutic aspects in rheumatoid arthritis.

Immunotherapy 2020 Aug 7;12(12):933-946. Epub 2020 Jul 7.

Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

The major current focus on treating rheumatoid arthritis is to put an end to long-term treatments and instead, specifically block widespread immunosuppression by developing antigen-specific tolerance, while also permitting an intact immune response toward other antigens to occur. There have been promising preclinical findings regarding adoptive Treg cells immunotherapy with a critically responsible function in the prevention of autoimmunity, tissue repair and regeneration, which make them an attractive candidate to develop effective therapeutic approaches to achieve this interesting concept in many human immune-mediated diseases, such as rheumatoid arthritis. or manipulation protocols are not only utilized to correct Treg cells defect, but also to benefit from their specific immunosuppressive properties by identifying specific antigens that are expressed in the inflamedjoint. The methods able to address these deficiencies can be considered as a target for immunity interventions to restore appropriate immune function.
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http://dx.doi.org/10.2217/imt-2020-0071DOI Listing
August 2020

Altering chromatin methylation patterns and the transcriptional network involved in regulation of hematopoietic stem cell fate.

J Cell Physiol 2020 10 13;235(10):6404-6423. Epub 2020 Feb 13.

Thalassemia and Hemoglobinopathy Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

Hematopoietic stem cells (HSCs) are quiescent cells with self-renewal capacity and potential multilineage development. Various molecular regulatory mechanisms such as epigenetic modifications and transcription factor (TF) networks play crucial roles in establishing a balance between self-renewal and differentiation of HSCs. Histone/DNA methylations are important epigenetic modifications involved in transcriptional regulation of specific lineage HSCs via controlling chromatin structure and accessibility of DNA. Also, TFs contribute to either facilitation or inhibition of gene expression through binding to enhancer or promoter regions of DNA. As a result, epigenetic factors and TFs regulate the activation or repression of HSCs genes, playing a central role in normal hematopoiesis. Given the importance of histone/DNA methylation and TFs in gene expression regulation, their aberrations, including changes in HSCs-related methylation of histone/DNA and TFs (e.g., CCAAT-enhancer-binding protein α, phosphatase and tensin homolog deleted on the chromosome 10, Runt-related transcription factor 1, signal transducers and activators of transcription, and RAS family proteins) could disrupt HSCs fate. Herewith, we summarize how dysregulations in the expression of genes related to self-renewal, proliferation, and differentiation of HSCs caused by changes in epigenetic modifications and transcriptional networks lead to clonal expansion and leukemic transformation.
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http://dx.doi.org/10.1002/jcp.29642DOI Listing
October 2020

The Effect of Demographic Factors and VKORC1 1639 G>A Genotypes on Estimated Warfarin Maintenance Dose in Iranian Patients Under Warfarin Therapy.

Indian J Hematol Blood Transfus 2019 Jan 1;35(1):167-171. Epub 2018 Aug 1.

5School of Paramedicine, Tehran Medical Branch of Islamic Azad University, P.O. Box 19395-1495, Tehran, Iran.

Warfarin is an anticoagulant that inhibits vitamin K-dependent clotting factors including factor (F) II, FVII, FIX and FX. Different factors can change the effect of this anticoagulant in clinic. Therefore we assessed impact of VKORC1 -1639 G>A polymorphism and demographic factors on required maintenance dose in Iranian patients under warfarin therapy. The study population included 95 patients with a mean age of 61.3 ± 12.6 years. Target INR range of 2-3 was considered for these patients. The frequency of VKORC1 -1639 G>A polymorphism was assessed by polymerase chain reaction-restriction length polymorphism (PCR-RFLP). Finally the obtain data were analyzed by SPSS software. Our study revealed that 30.5%, 49.5%, and 20% of the patients had VKORC1 (G/G), (G/A), and (A/A) genotypes, respectively. Carriers of VKORC1 G/G genotype required a higher warfarin dose as compared to A/A carriers (4.48 ± 1.32 and 2.7 ± 1.16 mg/day, respectively;  < 0.01). In addition, patients with higher age required lower warfarin therapeutic dose (r = - 0.3,  < 0.01). It seems that -1639 G>A polymorphism and demographic variables had significant effects on warfarin maintenance dose in Iranian patients under warfarin therapy.
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http://dx.doi.org/10.1007/s12288-018-0987-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6369093PMC
January 2019

Mixed-phenotype acute leukemia characteristics: first report from Iran.

Clin Exp Med 2018 Nov 17;18(4):513-521. Epub 2018 Jul 17.

Payvand Clinical and Specialty Laboratory, Tehran, Iran.

Mixed-phenotype acute leukemia (MPAL) is the infrequent type of acute leukemia characterized by immunophenotypic and/or cytochemical features of both lineages, but the diagnosis of this disease still is a challenge. In this study, we analyzed immunophenotyping, cytochemistry and frequency of MPAL patients to better diagnosis of MPAL characteristics according to WHO 2016 criteria for the first time in Iran. In this retrospective study, 27 patients were diagnosed as MPAL based on WHO 2016 criteria during 2014-2017. Flow cytometric immunophenotyping was performed on PB and BM samples evaluation of different CD marker expressions in MPAL subsets. RT-PCR was performed for the analyses of BCR/ABL1 fusion in MPAL subsets. Among 27 cases, (70.4%) 19 cases were B + My, (22.22%) 6 cases were T + My, and 2 cases (7.40%) were B + T + My. CD34, CD19, HLA-DR, TdT, CD22, iMPO were positive in majority of B + My cases. CD45, iMPO, iCD3, CD7, CD2 and CD5 were positive in majority of T + My cases. HLA-DR, TdT, CD10, CD22, iCD79a, iMPO, CD45, iCD3, CD7, CD3, CD2, CD5 were positive in majority of B + T + My cases. BCR/ABL1 fusion was positive for 3 cases (11.1%) of p190 fusion and 2 cases (7.4%) of p210 fusion in B + My cases. WHO 2016 criteria are the current standard for diagnosing MPAL. Also, evaluation of TdT, CD2, CD5, CD7 expressions by flow cytometry in EGIL criteria is useful for the better diagnosis of MPAL subsets. In addition, evaluation of BCR/ABL1 and MLL rearrangements in patients should be part of standard work-up in MPAL.
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http://dx.doi.org/10.1007/s10238-018-0520-7DOI Listing
November 2018

ASXL1 and JAK2V617F gene mutation screening in Iranian patients with chronic myeloid leukemia.

Asia Pac J Clin Oncol 2017 Apr 19;13(2):e41-e47. Epub 2016 Sep 19.

Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran.

Aim: In recent years, a few cases of chronic myeloid leukemia (CML) have been reported with both BCR-ABL and JAK2V617F mutations. Moreover, mutations in the additional sex comb-like 1 (ASXL1) gene were recently shown in various myeloid malignancies.There were no previous studies investigating the incidence of the ASXL1 and JAK2V617F mutations in Iranian patients with CML. Consequently, this study focuses on the analysis of these mutations in patients with CML.

Methods: In total, 66 patients with a clinical diagnosis of CML were examined at the time of diagnosis. Thirty healthy subjects were checked as controls. Exon 12 of ASXL1 was amplified from genomic DNA and bidirectionally sequenced. We also performed JAK2V617F screening by amplification refractory mutation system-polymerase chain reaction and sequencing.

Results: Mutations in the ASXL1 gene were found in five out of 66 CML patients (7.6%). We identified a novel variant (c.1968G > A, p.Asp656Asn) in one of the patients that has not been reported before. We also identified BCR-ABL and JAK2V617F mutations simultaneously in four patients (6%).

Conclusion: Our demonstration of ASXL1 mutation, a putative tumor suppressor gene, represents an important molecular abnormality in CML. We also showed that concomitant detection of BCR-ABL and JAK2V617F mutations has a relatively high incidence in Iranian patients.
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http://dx.doi.org/10.1111/ajco.12588DOI Listing
April 2017

Detection of Human Metapneumovirus and Respiratory Syncytial Virus by Real-Time Polymerase Chain Reaction Among Hospitalized Young Children in Iran.

Jundishapur J Microbiol 2016 Mar 15;9(3):e32974. Epub 2016 Mar 15.

Department of Pediatrics, Iran University of Medical Sciences, Tehran, IR Iran.

Background: Acute respiratory infection plays an important role in hospitalization of children in developing countries; detection of viral causes in such infections is very important. The respiratory syncytial virus (RSV) is the most common etiological agent of viral lower respiratory tract infection in children, and human metapneumovirus (hMPV) is associated with both upper and lower respiratory tract infections among infants and children.

Objectives: This study evaluated the frequency and seasonal prevalence of hMPV and RSV in hospitalized children under the age of five, who were admitted to Aliasghar children's hospital of Iran University of Medical Sciences from March 2010 until March 2013.

Patients And Methods: Nasopharyngeal or throat swabs from 158 hospitalized children with fever and respiratory distress were evaluated for RSV and hMPV RNA by the real-time polymerase chain reaction (PCR) method.

Results: Among the 158 children evaluated in this study, 49 individuals (31.1%) had RSV infection while nine individuals (5.7%) had hMPV infection. Five (55.5%) of the hMPV-infected children were male while four (44.5%) were female and 27 (55.2%) of the RSV-infected patients were females and 22 (44.8%) were males. The RSV infections were detected in mainly < one year old children and hMPV infections were detected mainly in > one year old children. Both RSV and hMPV infections had occurred mainly during winter and spring seasons.

Conclusions: Respiratory syncytial virus was the major cause of acute respiratory infection in children under one-year of age while human metapneumovirus had a low prevalence in this group. The seasonal occurrence of both viruses was the same.
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http://dx.doi.org/10.5812/jjm.32974DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4877467PMC
March 2016

Identification of CYP2C9 and VKORC1 polymorphisms in Iranian patients who are under warfarin therapy.

Int J Hematol Oncol Stem Cell Res 2015 Oct;9(4):185-92

MD, Payvand Clinical and Specialty Laboratory, Tehran, Iran.

Background: Although catalytic properties of different genetic polymorphisms of VKORC1 and CYP2C9 products have been identified, there is limited study available regarding warfarin dose requirement in Iranian patient population. This study investigates the impact of these polymorphisms on 115 patients, referred to Payvand Clinical and Specialty Laboratory for determining the appropriate dose of warfarin. RESULTS of the study may be applicable to individuals who are under warfarin therapy to avoid warfarin resistance or intolerance.

Subjects And Methods: PT-INR test was utilized as a screening method. Genotyping were performed for VKORC1 and CYP2C9 using PCR method. Statistical analyses including unpaired t-test or ANOVA and regression were done using SPSS.

Results: VKORC1 GA was the most common genotype of VKORC1 allele among the study samples, with a rate of 57.4%. In CYP2C9 variant, 20% and 14.8% of subjects carried CYP2C9*1/*2 and CYP2C9*1/*3 genotyping, respectively. By contrast, the WT *1/*1 genotype was more abundant and dominant. The high frequency of VKORC1 (_1639) GA genotype (57.4%), was significant versus for the rest of the cohort (42.6%). In addition, a significant relationship was found between CYP2C9*1 and drug dose (P>0.021).

Conclusion: In this study, samples were characterized by higher frequencies of CYP2C9*1 and VKORC1 G/A, determined as higher warfarin taking doses. The results showed a significant relationship of the VCORC1 and CYP2C9 polymorphisms with warfarin sensitivity and severe side effects. Estimating right doses of warfarin to prescribe can help to reduce the risk of over- or under-anticoagulation and subsequently, the risk of thromboembolism or bleeding.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4748690PMC
October 2015

Enzyme Polymorphism in Warfarin Dose Management After Pediatric Cardiac Surgery.

Res Cardiovasc Med 2015 Aug 1;4(3):e27963. Epub 2015 Aug 1.

Tehran Medical Sciences Branch, Islamic Azad University, Tehran, IR Iran.

Background: Warfarin is an anticoagulant and is widely used for the prevention of thromboembolic events. Genetic variants of the enzymes that metabolize warfarin, i.e. cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase (VKORC1), contribute to differences in patients' responses to various warfarin doses. There is, however, a dearth of data on the role of these variants during initial anticoagulation in pediatric patients.

Objectives: We aimed to evaluate the role of genetic variants of warfarin metabolizing enzymes in anticoagulation in a pediatric population.

Patients And Methods: In this prospective cohort study, 200 pediatric patients, who required warfarin therapy after cardiac surgery, were enrolled and divided into two groups. For 50 cases, warfarin was prescribed based on their genotyping (group 1) and for the remaining 150 cases, warfarin was prescribed based on our institute routine warfarin dosing (group 2). The study endpoints were comprised of time to reach the first therapeutic international normalization ratio (INR), time to reach a stable warfarin maintenance dose, time with over-anticoagulation, bleeding episodes, hospital stay days and stable warfarin maintenance dose.

Results: There was no significant difference concerning the demographic data between the two groups. The time to stable warfarin maintenance dose and hospital stay days were significantly lower in group 1 (P <0.001). However, there was no statistically significant difference in time to reach the first therapeutic INR, time with over-anticoagulation and bleeding episodes, between the two groups.

Conclusions: The determination of warfarin dose, based on genotyping, might reduce the time to achieve stable anticoagulation of warfarin dose and length of hospital stay.
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http://dx.doi.org/10.5812/cardiovascmed.27963v2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4592525PMC
August 2015

Characterizing of Four Common BCR-ABL Kinase Domain Mutations (T315I, Y253H, M351T and E255K) in Iranian Chronic Myelogenous Leukemia Patients With Imatinib Resistance.

Iran J Cancer Prev 2015 May 27;8(3):e2334. Epub 2015 May 27.

MSc in Biotechnology, Payvand Clinical and Specialty Laboratory,Tehran, IR Iran.

Background: Chronic myelogenous leukemia (CML) is a kind of hematopoietic stem-cell cancer. A significant number of CML patients who do not achieve an acceptable response to therapy, show acquired resistance against Imatinib. One of the most considerable causes of resistance against Imatinib as the first line of therapy, are BCR-ABL kinase domain mutations.

Objectives: One of the most considerable causes of resistance against Imatinib as the first line of therapy, are BCR-ABL kinase domain mutations.

Patients And Methods: The study was performed on 39 CML patients with Imatinib resistance. Basic hematologic parameters in blood samples were checked to identify hematologic response. To identify molecular response, BCR-ABL/ABL ratio was assessed by Real-time PCR. The ABL kinase domain amplification was performed by PCR. Restriction fragment length polymorphism (RFLP) was performed to detect four common mutations (T315I, Y253H, E255K and M351T). Finally the results were approved by direct sequencing.

Results: In this study, the Y253H mutation, detected by RFLP method and confirmed by direct sequencing, was the prevalent ABL kinase domain mutation in these 39 CML patients. The G250E, V379I and L384M mutations were found in three different cases with failure molecular response. CML patients with these four ABL kinase domain mutations cannot achieve major molecular response (MMR). In addition, complete hematologic response (CHR) was observed only in the V379I mutated case and not in other mutated patients.

Conclusions: Identification of ABL kinase domain mutations may be used as a proper and useful method for improving therapeutic strategies, avoiding delay in treatment and excessive expenditure in CML patients with Imatinib resistance.
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http://dx.doi.org/10.17795/ijcp2334DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4581365PMC
May 2015

PCR Analysis of IgH and TCR-γ Gene Rearrangements as a Confirmatory Diagnostic Tool for Lymphoproliferative Disorders.

Indian J Hematol Blood Transfus 2015 Mar 4;31(1):38-45. Epub 2014 May 4.

Health Research Institute, Research Center of Thalassemia and Hemoglobinopathy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

This study investigates PCR analysis of immunoglobulin heavy chain (IgH) and T cell receptor (TCR) gene rearrangements on paraffin-embedded tissue sections and bone marrow aspirates of patients suspected to have lymphoproliferative disorders but with inconclusive diagnosis in histopathological examination. 130 samples of patients with inconclusive immunohistochemistry results were evaluated for clonal rearrangement of IgH and TCR genes. Based on histopathology examination, the patients were divided into three groups: the first group without any definite diagnosis of lymphoproliferative disorders (60 cases, 46.2 %), the second group suspected to have a lymphoproliferative disorder but in favor of benign disorders (19 cases, 14.6 %) and the third group suspect to lymphoproliferative disorders but relatively in favor of malignant disorders (51 cases, 39.2 %). After DNA extraction and quality control, semi-nested PCR was performed using consensus primers for amplification of TCR-γ and CDR-3 regions of IgH genes. PCR products were analyzed after heteroduplex analysis using polyacrylamide gel electrophoresis, and were subject to silver staining. Totally, in over half of the cases (55.4 %), a monoclonal pattern was found in IgH or TCR-γ genes rearrangements. Monoclonal IgH gene rearrangement was detected in 48.1 % of patients, whereas monoclonal TCR-γ gene rearrangement was found in 33.6 % of them, which was not statistically significant (P = 0.008). Only in 32 patients (24.6 %) were the results of TCR-γ and IgH gene rearrangements consistent with respect to the presence (2.3 %) or absence (22.3 %) of monoclonality. Finally, PCR analysis of TCR-γ and IgH gene rearrangements led to definite diagnosis in 105 patients (80.8 %), and only 25 cases (19.2 %) remained inconclusive. Our results emphasize the usefulness of gene rearrangement study in cases without a definite diagnosis in immunohistochemistry studies. Multiple PCR analysis results when combined with patient's clinical course and immunohistochemistry can lead to early diagnosis and subsequent therapy.
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http://dx.doi.org/10.1007/s12288-014-0387-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4275529PMC
March 2015

Polymorphism and synergism of angiotensin-converting enzyme (ACE) and plasminogen activator inhibitor-1 (PAI-1) genes in coronary artery disease.

J Renin Angiotensin Aldosterone Syst 2015 Dec 12;16(4):1168-74. Epub 2014 Dec 12.

Iran University of Medical Sciences, Iran

Introduction: Among the genetic factors for coronary artery diseases, PAI-1 4G/5G and ACE I/D polymorphisms can be noted. This study was carried out to investigate the association of these two polymorphisms and their synergism in coronary artery disease (CAD) from a sample of the Iranian population.

Materials And Methods: Sixty-one patients with a history of CAD and 92 healthy controls participated in our study. After DNA extraction from leukocytes, PCR was performed to characterize PAI-1 4G/5G and ACE I/D polymorphisms, using an amplification refractory mutation system technique.

Results: In the studied patients, PAI-1 polymorphisms were 24.6%, 45.9%, and 29.5% for 4G/4G, 4G/5G and 5G/5G, respectively; the values for controls were 20.7%, 42.2% and 37.0%. The distribution rates of genotypes I/I, I/D and D/D in patients accounted for 29.5%, 45.9% and 24.6%; in the control group these figures were estimated to be 40.2%, 40.2% and 19.6%.

Conclusion: Single and multivariate analyses showed a significant difference for the conventional risk factors, including hypertension, diabetes, hyperlipidemia, smoking and family history, for CAD between patients and controls (p value ≤ 0.001). However, no significant correlation was demonstrated considering ACE and PAI-1 polymorphisms either in association with 4G/4G or D/D genotypes or a combination of them in the Iranian population in the current study.
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http://dx.doi.org/10.1177/1470320314561247DOI Listing
December 2015

Prevalence of ETV6/RUNX1 Fusion Gene in Pediatric Patients with Acute Lymphoblastic Leukemia in Iran.

Iran J Pediatr 2013 Dec;23(6):681-6

Institute of Molecular Biology NAS RA, Yerevan, Armenia.

Objective: ETV6/RUNX1 (also known as TEL/AML1) is the most frequent gene fusion in childhood acute lymphoblastic leukemia (ALL). Sixty-three patients were enrolled in this study to explore the distribution of this gene in Iranian population.

Methods: This study used 63 peripheral blood and bone marrow (PB/BM) samples from children with ALL. Immunophenotyping of PB and BM samples were performed using flow cytometry to illustrate the lineage. Moreover, reverse transcriptase polymerase chain reaction (RT-PCR) technique was used to amplify transcripts of leukemia-specific chromosome fusion gene ETV6/RUNX1 and to monitor the expression levels of the ETV6/RUNX1 in patients according to Van Dongen et al protocol.

Findings: On the basis of French-American-British (FAB) classification, 47 individuals had ALL-L1. The incidence of ETV6/RUNX1 fusion gene in this study was 34.9%. The laboratory and clinical features of twenty two ETV6/RUNX1 positive ALL cases were similar to those of other studies. The most positive cases of ETV6/RUNX1 fusion gene had the early pre B ALL and pre B ALL immunophenotypes.

Conclusion: The ETV6/RUNX1 fusion gene is a common genetic anomaly in Iranian childhood ALL patients and the prevalence of the ETV6/RUNX1 fusion gene is similar to that of ALL patients in other countries. However early pre B cells were the most common type in studied patients.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4025127PMC
December 2013

Pattern of immunoglobulin and T-cell receptor-δ/γ gene rearrangements in Iranian children with B-precursor acute lymphoblastic leukemia.

Hematology 2014 Jul 3;19(5):259-66. Epub 2014 Jan 3.

Introduction: Acute lymphoblastic leukemia (ALL) cells have unique rearranged immunoglobulin heavy chain (IgH), immunoglobulin light chain (IgK), and T-cell receptor (TCR) genes, which can be used as markers for clonality assay and evaluation of minimal residual disease. In this study, we have evaluated the pattern of IgH, IgK chains, and TCRG/D gene rearrangements in precursor-B ALL.

Materials And Methods: In our prospective study, hyper-variable regions (CDRI and III) of IgH, TCRD (Vδ2-Dδ3 and Dδ2-Dδ3), TCRG (Vγ, VγI, and VγII), and IgK (Vκ-Kde) were studied in 126 cases with diagnosis of B-precursor ALL.

Results: One hundred and fourteen (90.5%) out of 126 patients had clonal rearrangements of IgH using consensus primers for CDRI and/or CDRIII regions. Monoclonal, biclonal, and oligoclonal patterns were observed in 63 (57.8%), 38 (34.9%), and 6 (5.5%) patients with IgH (CDRIII) rearrangements, respectively. Clonal rearrangements of TCRG (Vγ) and VγI/II were present in 79.3 and 64.9% of patients, respectively, and only 5% of cases showed biclonal pattern. The VγII rearrangement was the most common (46.8%) type in TCRG. Vδ2-Dδ3 and Dδ2-Dδ3 partial gene rearrangements were observed in 47 (45.2%; n = 104) and 11 (16.6%; n = 66) patients, respectively. Biclonal/oligoclonal patterns were present in 13 (27.7%) and 2 (4.3%) cases with Vδ2-Dδ3 rearrangement, respectively. Only one patient had biclonal Dδ2-Dδ3 rearrangement. Clonal pattern of IgK-Kde was detected in 59 cases (67%; n = 88).

Conclusion: Our findings showed that clonal rearrangements of IgH and TCRD (Vδ2-Dδ3 and Dδ2-Dδ3) genes had similar patterns to other studies. Frequency of TCRG (VγI and VγII) and IgK rearrangements was found to be slightly higher than previous reports. Among the IgK rearrangements, VKI (25%) was the most common.
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http://dx.doi.org/10.1179/1607845413Y.0000000126DOI Listing
July 2014

Investigation of deregulated genes of Notch signaling pathway in human T cell acute lymphoblastic leukemia cell lines and clinical samples.

Mol Biol Rep 2013 Oct 29;40(10):5531-40. Epub 2013 Aug 29.

Molecular Medicine Department, Biotechnology Research Center, Pasteur Institute of Iran, P.O.Box 1316943551, Tehran, Iran.

In diagnostic research challenges, quantitative real-time PCR (QPCR) has been widely utilized in gene expression analysis because of its sensitivity, accuracy, reproducibility, and most importantly, quantitativeness. Real-time PCR base kits are wildly applicable in cancer signaling pathways, especially in cancer investigations. T-cell acute lymphoblastic leukemia (T-ALL) is a type of leukemia that is more common in older children and teenagers. Deregulation of the Notch signaling pathway promotes proliferation and inhibits apoptosis of the lymphoblastic T cells. The aim of this study was to investigate the effect of Notch signaling activation on the expression of target genes using real-time QPCR and further use this method in clinical examination after validation. Two T-ALL cell lines, Jurkat and Molt-4, were used as models for activation of the Notch signaling via over-expression of the Notch1 intracellular domain. Expression analysis was performed for six downstream target genes (NCSTN, APH1, PSEN1, ADAM17, NOTCH1 and C-MYC) which play critical roles in the Notch signaling pathway. The results showed significant difference in the expression of target genes in the deregulated Notch signaling pathway. These results were also verified in 12 clinical samples bearing over-expression of the Notch signaling pathway. Identification of such downstream Notch target genes, which have not been studied inclusively, provides insights into the mechanisms of the Notch function in T cell leukemia, and may help identify novel diagnoses and therapeutic targets in acute lymphoblastic leukemia.
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http://dx.doi.org/10.1007/s11033-013-2654-8DOI Listing
October 2013