Publications by authors named "Najmaldin Saki"

129 Publications

The IFN-Ɣ + 874 A/T polymorphism is associated with malignant breast cancer in a population from the southwest of Iran.

BMC Res Notes 2021 Apr 20;14(1):147. Epub 2021 Apr 20.

Hyperlipidemia Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

Objective: Breast cancer (BC) is one of the most common diseases in women globally, with an increasing number of deaths associated with it. Recently the role of polymorphisms in the genes encoding cytokines and immune cells has been demonstrated. This study aimed to evaluate the association of IFN-Ɣ + 874 A/T polymorphism with BC clinical symptoms.

Results: The study included 88 women with BC and 88 healthy women who had no history of cancer and were matched for age and sex. Allele-specific oligonucleotide-polymerase chain reaction technique was used to investigate the IFN-Ɣ polymorphism. Clinical data were obtained from the patients' records. Our results showed that the frequencies of genotypes in the BC patients were not significantly different from the control subjects. However, in the patients, the AT genotype was associated with the risk of malignant BC. The age at BC diagnosis was not different in patients with AA and AT genotypes; however, it was significantly earlier in HER2 negative subjects (p = 0.002). Given the higher frequency of AT in malignant BC patients, our results confirm the association of the IFN-Ɣ polymorphism with the disease's progression to a malignant state.
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http://dx.doi.org/10.1186/s13104-021-05543-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056653PMC
April 2021

COVID-19: imbalance of multiple systems during infection and importance of therapeutic choice and dosing of cardiac and anti-coagulant therapies.

Mol Biol Rep 2021 Mar 10;48(3):2917-2928. Epub 2021 Apr 10.

Golestan Hospital Clinical Research Development Unit, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

The renin-angiotensin-aldosterone system and its metabolites play an important role in homeostasis of body, especially the cardiovascular system. In this study, we discuss the imbalance of multiple systems during the infection and the importance of therapeutic choice, dosing, and laboratory monitoring of cardiac and anti-coagulant therapies in COVID-19 patients. The crosstalk between angiotensin, kinin-kallikrein system, as well as inflammatory and coagulation systems plays an essential role in COVID-19. Cardiac complications and coagulopathies imply the crosstalks between the mentioned systems. We believe that the blockage of bradykinin can be a good option in the management of COVID-19 and CVD in patients and that supportive treatment of respiratory and cardiologic complications is needed in COVID-19 patients. Ninety-one percent of COVID-19 patients who were admitted to hospital with a prolonged aPTT were positive for lupus anticoagulant, which increases the risk of thrombosis and prolonged aPTT. Therefore, the question that is posed at this juncture is whether it is safe to use the prophylactic dose of heparin particularly in those with elevated D-dimer levels. It should be noted that timing is of high importance in anti-coagulant therapy; therefore, we should consider the level of D-dimer, fibrinogen, drug-drug interactions, and risk factors during thromboprophylaxis administration. Fibrinogen is an independent predictor of resistance to heparin and should be considered before thromboprophylaxis. Alteplase and Futhan might be a good choice to assess the condition of heparin resistance. Finally, the treatment option, dosing, and laboratory monitoring of anticoagulant therapy are critical decisions in COVID-19 patients.
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http://dx.doi.org/10.1007/s11033-021-06333-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035598PMC
March 2021

Aspirin exacerbated respiratory disease (AERD): molecular and cellular diagnostic & prognostic approaches.

Mol Biol Rep 2021 Mar 24;48(3):2703-2711. Epub 2021 Feb 24.

Department of Pathology, Vali-E-Asr Hospital, School of Medicine, Zanjan University of Medical Science, Zanjan, Iran.

Aspirin-exacerbated respiratory disease (AERD) is characterized by immune cells dysfunction. This study aimed to investigate the molecular mechanisms involved in AERD pathogenesis. Relevant literatures were identified by a PubMed search (2005-2019) of english language papers using the terms "Aspirin-exacerbated respiratory disease", "Allergic inflammation", "molecular mechanism" and "mutation". According to the significant role of inflammation in AERD development, ILC-2 is known as the most important cell in disease progression. ILC-2 produces cytokines that induce allergic reactions and also cause lipid mediators production, which activates mast cells and basophils, ultimately. Finally, Monoclonal antibody and Aspirin desensitization in patients can be a useful treatment strategy for prevention and treatment.
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http://dx.doi.org/10.1007/s11033-021-06240-0DOI Listing
March 2021

The effect of inflammatory factors and their inhibitors on the hematopoietic stem cells fate.

Cell Biol Int 2021 May 21;45(5):900-912. Epub 2021 Jan 21.

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

Inflammatory cytokines exert different effects on hematopoietic stem cells (HSCs), lead to the development of various cell lineages in bone marrow (BM) and are thus a differentiation axis for HSCs. The content used in this article has been obtained by searching PubMed database and Google Scholar search engine of English-language articles (1995-2020) using "Hematopoietic stem cell," "Inflammatory cytokine," "Homeostasis," and "Myelopoiesis." Inflammatory cytokines are involved in the differentiation and proliferation of hematopoietic progenitors to compensate for cellular death due to inflammation. Since each of these cytokines differentiates HSCs into a specific cell line, the difference in the effect of these cytokines on the fate of HSC progenitors can be predicted. Inhibitors of these cytokines can also control the inflammatory process as well as the cells involved in leukemic conditions. In general, inflammatory signaling can specify the dominant cell line in BM to counteract inflammation and leukemic condition via stimulating or inhibiting hematopoietic progenitors. Therefore, detection of the effects of inflammatory cytokines on the differentiation of HSCs can be an appropriate approach to check inflammatory and leukemic conditions and the suppression of these cytokines by their inhibitors allows for control of homeostasis in stressful conditions.
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http://dx.doi.org/10.1002/cbin.11545DOI Listing
May 2021

Flow cytometric Immunophenotyping and Hematological Findings at Diagnosis and Relapse of Pediatric Acute Lymphoblastic Leukemia Patients.

Clin Lab 2020 Dec;66(12)

Background: Acute lymphoblastic leukemia (ALL) is a common pediatric leukemia caused by lymphoid precursor proliferation. We analyzed immunophenotyping and hematological findings, as the risk of relapse, of pediatric ALL patients at diagnosis and relapse.

Methods: Peripheral blood and bone marrow samples of 30 pediatric ALL patients were collected at diagnosis and at relapse. The latter was evaluated for immunophenotyping and cytochemical staining (Periodic Acid Schiff stain (PAS)), while hematological findings were assessed in the former one.

Results: The percentage of PAS-positive patients, TdT, and CD4 expression were significantly higher at diagnosis than relapse (p = 0.027, 0.004, and 0.043, respectively), whereas the platelet/lymphocyte ratio (PLR) and neutrophil/lymphocyte ratio were significantly lower at diagnosis (p = 0.004 and 0.032, respectively). There were correla-tions between immunophenotyping and hematology data, including: a) a negative correlation between CD4 expression with blast percentage (r = -0.927, p = 0.003) and hemoglobin level (r = -0.991, p < 0.001) at diagnosis and TdT expression with platelet count (r = -0.441, p = 0.017) at relapse, and b) a positive correlation between CD3 expression with PLR (r = 0.367, p = 0.046) at relapse.

Conclusions: Results suggest that changes in immunophenotyping and hematology findings could be applied as relapse prognostic factors in ALL.
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http://dx.doi.org/10.7754/Clin.Lab.2020.200340DOI Listing
December 2020

Chemo/radiotherapy-Induced Bone Marrow Niche Alterations.

Cancer Invest 2021 Feb 10;39(2):180-194. Epub 2020 Dec 10.

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

Bone marrow (BM) niche is a specific microenvironment for hematopoietic stem cells (HSCs) as well as non-hematopoietic cells. Evidence shows that chemo/radiotherapy can lead to the disruption of different properties of HSCs such as proliferation, differentiation, localization, self-renewa, and steady-state of cell populations. Investigations have shown that the deregulation of balance within the marrow cavity due to chemo/radiotherapy could lead to bone loss, abnormal hematopoiesis, and enhanced differentiation potential of mesenchymal stem cells towards the adipogenic lineage. Therefore, understanding the underlying mechanisms of chemo/radiotherapy induced BM niche changes may lead to the application of appropriate therapeutic agents to prevent BM niche defects. Highlights Chemo/radiotherapy disrupts the steady-state of bone marrow niche cells and result in deregulation of normal balance of stromal cell populations. Chemo/radiotherapy agents play a significant role in reducing of bone formation as well as fat accumulation in the bone marrow niche. Targeting molecular pathways may lead to recovery of bone marrow niches after chemo/radiotherapy.
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http://dx.doi.org/10.1080/07357907.2020.1855353DOI Listing
February 2021

Digging deeper through glucose metabolism and its regulators in cancer and metastasis.

Life Sci 2021 Jan 20;264:118603. Epub 2020 Oct 20.

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

Glucose metabolism enzymes and transporters play major role in cancer development and metastasis. In this study, we discuss glucose metabolism, transporters, receptors, hormones, oncogenes and tumor suppressors which interact with glucose metabolism and we try to discuss their major role in cancer development and cancer metabolism. We try to highlight the. Metabolic changes in cancer and metastasis upregulation of glycolysis is observed in many primary and metastatic cancers and aerobic glycolysis is the most favorable mechanism for glucose metabolism in cancer cells, and it is a kind of evolutionary change. The question that is posed at this juncture is: Can we use aerobic glycolysis phenotype and enzymes beyond this mechanism in estimating cancer prognosis and metastasis? Lactate is a metabolite of glucose metabolism and it is a key player in cancer and metastasis in both normoxic and hypoxic condition so lactate dehydrogenase can be a good prognostic biomarker. Furthermore, monocarboxylic transporter which is the main lactate transporter can be good target in therapeutic studies. Glycolysis enzymes are valuable enzymes in cancer and metastasis diagnosis and can be used as therapeutic targets in cancer treatment. Designing a diagnostic and prognostic profile for cancer metastasis seems to be possible base on glycolysis enzymes and glucose transporters. Also, glucose metabolism enzymes and agents can give us a clear vision in estimating cancer metastasis. We can promote a panel of genes that detect genetic changes in glucose metabolism agents to diagnose cancer metastasis.
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http://dx.doi.org/10.1016/j.lfs.2020.118603DOI Listing
January 2021

The role of exogenous Fibrinogen in cardiac surgery: stop bleeding or induce cardiovascular disease.

Mol Biol Rep 2020 Oct 7;47(10):8189-8198. Epub 2020 Oct 7.

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

The surgical treatment contributes to broad variety of cardiovascular diseases (CVD). Due to many involved factors in preoperative bleeding, it is almost difficult to perform better Haemostatic approach. Fibrinogen is a major blood glycoprotein and a coagulation factor which decreases postoperative bleeding. It has a potential role in platelet activation and bleeding inhibition; it may reflect the inflammatory responses and be related to the endothelial dysfunction. Fibrinogen can act as a pro-inflammatory element via increasing some inflammatory markers including IL-6, tumor necrosis factor-α (TNF-α), monocyte chemo attractant protein (MCP-1), macrophage inflammatory protein-1 (MIP-1a and b), matrix metalloproteinase (MMP-1 and MMP-9) and Toll-like Receptors (TLRs); through activation of these factors, fibrinogen may induce some inflammatory mechanisms such as focal adhesion kinase (FAK), mitogen-activated protein kinases (MAPK) and nuclear factor κB (NF-κB) pathways. It may cause endothelial dysfunction by increasing P and E-selection, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) levels which activate MAPK and NF-κB pathways. This factor is also associated with increased exocytosed von Willebrand factor (vWF) as well as activation of Rho-GTPase mechanism. All of these data demonstrate the dual role of fibrinogen in cardiac surgeries, bleeding inhibition and CVD. Therefore, identifying the CVD factors is helpful for designing preventive strategies and alternative drugs.
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http://dx.doi.org/10.1007/s11033-020-05880-yDOI Listing
October 2020

DNA repair pathways as guardians of the genome: Therapeutic potential and possible prognostic role in hematologic neoplasms.

DNA Repair (Amst) 2020 12 15;96:102951. Epub 2020 Aug 15.

Department of Hematology and Blood Banking, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran; Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran. Electronic address:

DNA repair pathways, which are also identified as guardians of the genome, protect cells from frequent damage that can lead to DNA breaks. The most deleterious types of damage are double-strand breaks (DSBs), which are repaired by homologous recombination (HR) and non-homologous end joining (NHEJ). Single strand breaks (SSBs) can be corrected through base excision repair (BER), nucleotide excision repair (NER), and mismatch repair (MMR). Failure to restore DNA lesions or inappropriately repaired DNA damage culminates in genomic instability and changes in the regulation of cellular functions. Intriguingly, particular mutations and translocations are accompanied by special types of leukemia. Besides, expression patterns of certain repair genes are altered in different hematologic malignancies. Moreover, analysis of mutations in key mediators of DNA damage repair (DDR) pathways, as well as investigation of their expression and function, may provide us with emerging biomarkers of response/resistance to treatment. Therefore, defective DDR pathways can offer a rational starting point for developing DNA repair-targeted drugs. In this review, we address genetic alterations and gene/protein expression changes, as well as provide an overview of DNA repair pathways.
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http://dx.doi.org/10.1016/j.dnarep.2020.102951DOI Listing
December 2020

Co-existence of mutations in myeloproliferative neoplasms and their clinical significance: a prognostic approach.

Expert Rev Hematol 2020 11 29;13(11):1289-1301. Epub 2020 Sep 29.

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

Objective: Myeloproliferative neoplasms (MPNs) are a group of clonal hematopoietic stem cell disorders that may occur after one or more mutations in hematopoietic progenitor cells. In this study, we will review the co-existence of mutations (especially dual mutations) in MPNs and its effect on the prognosis of patients.

Methods: To find relevant published papers, we systematically searched six major international indexing databases, namely PubMed/Medline, EmBase, Cochrane central, ISI web of science, and Scopus from Feb. 2000 until Jan. 2020. We included the following keywords in the analyzes: Myeloproliferative Disorders, Mutation, Co-existence of Mutations, Acute myeloid leukemia.

Results: Co-existence of several mutations in MPNs is mainly associated with a poor prognosis compared with the unimutated MPN disorders. There are several effective factors such as sequence of mutations, incidence of mutations in one cell or different cells, mutation, and MPN type.

Conclusion And Expert Commentary: It seems that monitoring the status of mutations in MPNs and recognizing the co-existence of mutations (especially dual mutations) in order to determine prognosis and possibility of progression to acute form of leukemia can lead to the prediction of prognosis in MPN patients as well as establishment of better and more reliable therapeutic strategies for patients.
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http://dx.doi.org/10.1080/17474086.2020.1819232DOI Listing
November 2020

Evaluation of immunophenotypic markers and clinico-hematological profile in chronic lymphocytic leukemia: implications for prognosis.

BMC Res Notes 2020 Sep 3;13(1):412. Epub 2020 Sep 3.

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

Objective: Chronic lymphocytic leukemia (CLL) is an adult leukemia presented with clonal accumulation of lymphocytes. Immunophenotypic changes can be effective in predicting clinical course, the survival of patients, and determining first-line treatment. This is a study of the association between immunophenotypic markers with complete blood cell count (CBC) values and clinical parameters.

Results: Peripheral blood samples were collected from 35 newly diagnosed CLL patients. The expression of immunophenotypic markers and CBC were evaluated. Platelet counts and hemoglobin concentration had a significant, inverse association with Rai staging, modified Rai staging, Binet staging systems (all p < 0.001 in both parameters), and splenomegaly (p = 0.001 and 0.007, respectively). The platelet/lymphocyte ratio (PLR) had a significant, inverse association with Rai staging (p = 0.014), modified Rai staging (p = 0.024), Binet staging systems (p = 0.027), and splenomegaly (p = 0.033). However, CD38, CD25, and double-positive CD56/CD117 expression, group 3 of innate lymphocyte cells (ILC3s), had no significant association with clinical parameters. In regression analysis, that ILC3s has an inverse correlation with neutrophil/lymphocyte ratio (r = -0.340, p = 0.046). Given that there is an inverse association between PLR and advanced clinical stages, it seems that PLR may have prognostic value in CLL.
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http://dx.doi.org/10.1186/s13104-020-05243-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7469386PMC
September 2020

CD markers polymorphisms as prognostic biomarkers in hematological malignancies.

Oncol Rev 2020 Jul 14;14(2):466. Epub 2020 Jul 14.

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

The clusters of differentiation (CD) are surface molecules used for immunophenotyping of cells. The expression of CD markers is widely used to classify hematological malignancies, including leukemia and lymphoma. Single nucleotide polymorphisms (SNPs) are crucial genetic changes that can be associated with abnormal expression and function of CD markers. In this paper, we assess the prognostic effect of CD markers SNPs in hematological malignancies. Materials and methods and relevant literature was identified by a PubMed search (2001-2019) of English language papers using the following terms: 'polymorphism', 'CD marker', 'leukemia', 'lymphoma', 'prognosis', 'CD marker', and 'polymorphism'. Many studies have demonstrated the effects of CD markers polymorphisms on risk of hematological malignancies. Also, SNPs of CD markers can be related with clinicopathological features, invasiveness, and response to therapy of these disorders. Considering the importance of SNPs in the expressions of CD markers, these genetic changes could be used as potential prognostic biomarkers in hematological malignancies. It is hoped that the evaluation of SNPs in CD markers will enable early diagnosis, prognosis, and detection of response to treatment. However, better understanding of SNPs in CD markers that are involved in hematological malignancies requires further studies on different populations of the worldwide.
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http://dx.doi.org/10.4081/oncol.2020.466DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7385526PMC
July 2020

Essential thrombocythemia: a hemostatic view of thrombogenic risk factors and prognosis.

Mol Biol Rep 2020 Jun 30;47(6):4767-4778. Epub 2020 May 30.

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

Essential thrombocythemia (ET) is a classical myeloproliferative neoplasm that is susceptible to hypercoagulable state due to impaired hemostatic system, so that thrombotic complications are the leading cause of mortality in ET patients. The content used in this article has been obtained by the PubMed database and Google Scholar search engine from English-language articles (2000-2019) using the following keywords: "Essential thrombocythemia," "Thrombosis," "Risk factors" and "Hemostasis. In this neoplasm, the count and activity of cells such as platelets, leukocytes, endothelial cells, as well as erythrocytes are increased, which can increase the risk of thrombosis through rising intercellular interactions, expression of surface markers, and stimulation of platelet aggregation. In addition to these factors, genetic polymorphisms in hematopoietic stem cells (HSCs), including mutations in JAK2, CALR, MPL, or genetic abnormalities in other genes associated with the hemostatic system may be associated with increased risk of thrombotic events. Moreover, disruption of coagulant factors can pave the way for thrombogeneration. Therefore, the identification of markers related to cell activation, genetic abnormalities, or alternation in the coagulant system can be used together as diagnostic and prognostic markers for the occurrence of thrombosis among ET patients. Thus, because thrombotic complications are the main factors of mortality in ET patients, a hemostatic viewpoint and risk assessment of cellular, genetic, and coagulation factors can have prognostic value and contribute to the choice of effective treatment and prevention of thrombosis.
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http://dx.doi.org/10.1007/s11033-020-05536-xDOI Listing
June 2020

PEAR1 polymorphisms as a prognostic factor in hemostasis and cardiovascular diseases.

J Thromb Thrombolysis 2021 Jan;51(1):89-95

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

Platelet Endothelial Aggregation Receptor (PEAR1), as a platelet receptor, plays a vital role in hemostasis. This receptor, by its extracellular part, causes platelet adhesion and consequently initiates platelet aggregation. Dysfunction of PEAR1 can disrupt platelet aggregation in patients with cardiovascular diseases (CVDs). The content used in this paper has been taken from English language articles (2005-2020) retrieved from Pubmed database and Google scholar search engine using "Cardiovascular Disease", "PEAR1", "Polymorphism", and "Platelet Aggregation" keywords. Some PEAR1 polymorphisms can disrupt homeostasis and interfere with the function mechanism of cardiac drugs. Since polymorphisms in this gene affect platelet function and the platelet aggregation process, PEAR1 could be further studied in the future as an essential factor in controlling the treatment process of patients with cardiovascular diseases. PEAR1 polymorphisms through disruption of the platelet aggregation process can be a risk factor in patients with CVDs. Therefore, controlling patients through genetic testing and the evaluation of PEAR1 polymorphisms can help improve the treatment process of patients. According to the studies on the PEAR1 gene and the effect of different polymorphisms on some crucial issues in CVDs patients (changes in platelet activity), it is clear that if there is a significant relationship between polymorphisms and CVDs, they can be used as prognostic and diagnostic markers. This study aims to evaluate the prognosis and drug treatment of the PEAR1 gene in CVDs patients.
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http://dx.doi.org/10.1007/s11239-020-02149-wDOI Listing
January 2021

Prognostic role and therapeutic susceptibility of cathepsin in various types of solid tumor and leukemia: A systematic review.

J Cell Physiol 2020 11 23;235(11):7709-7730. Epub 2020 Apr 23.

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

Cathepsins (CTSs) are multifunctional proteins that can play prominent roles in cancer progression and metastasis. In this systematic review, we compared the prognosis of CTS subtypes overexpression in leukemia and solid tumors, and investigated the effect of different factors on CTS prognosis. We systematically searched published articles indexed in PubMed, Scopus, Cochrane library, ISI Web of Science, and EmBase databases from February 2000 until January 2020. Among the selected leukemia and solid tumors studies, overexpression of CTS subtypes in newly diagnosed and treated patients were with poor prognosis in 43 studies (79.6%) and with good prognosis in 9 studies (16.6%). However, there were 2 studies (3.8%) with either good or poor prognosis, depending on conditions and caner stage and host cell. The relation between CTS and human leukocyte antigen (HLA) in leukemia and solid tumors was mentioned in 7 studies (13%). Overexpression of CTS subtypes in all new case patients had contributed to the induction of poor prognosis. It seems that CTS subtypes, based on the type of cancer and its stage, the type of host cells, and the probable relation with HLA, breed good or poor prognosis in patients with cancer. Therefore, monitoring the overexpression of CTS subtypes and determining the effect of each of these factors on CTS prognosis could be helpful in predicting cancer prognosis both in newly diagnosed or under treatment patients. They could also be useful in finding ways for improving the efficiency of contemporary therapeutic strategies in various types of leukemia and solid tumors.
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http://dx.doi.org/10.1002/jcp.29710DOI Listing
November 2020

Cardiomyopathy in Thalassemia: Quick Review from Cellular Aspects to Diagnosis and Current Treatments.

Lab Med 2020 Mar;51(2):143-150

Child Growth & Development Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.

Background: Cardiomyopathic manifestations induced by continuous blood transfusion are the leading cause of death among patients with thalassemia major (TM). Despite introduction of chelation therapy, heart failure after cardiomyopathic manifestations is still a major threat to patients.

Methods: We performed a search of relevant English-language literature, retrieving publications from the PubMed database and the Google Scholar search engine (2005-2018). We used "thalassemia major", "cardiomyopathy", "iron overload", "cardiac magnetic resonance T2" "chelation therapy", and "iron burden" as keywords.

Results: The results of the studies we found suggest that cardiac hepcidin is a major regulator of iron homeostasis in cardiac tissue. Unlike previous assumptions, the heart appears to have a limited regeneration capability, originating from a small population of hypoxic cardiomyocytes.

Conclusions: Oxygen levels determine cardiomyocyte gene-expression patterns. Upregulation of cardiac hepcidin in hypoxia preserves cardiomyocytes from forming out of reactive oxygen species catalyzed by free cellular iron in cardiomyocytes. Using the limited regeneration capacity of cardiac cells and gaining further understanding of the cellular aspects of cardiomyopathic manifestations may help health care professionals to develop new therapeutic strategies.
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http://dx.doi.org/10.1093/labmed/lmz052DOI Listing
March 2020

T-Cell Molecular Modulation Responses in Atherosclerosis Anergy.

Lab Med 2020 Nov;51(6):557-565

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

Atherosclerosis continues to be a major cause of death in patients with cardiovascular diseases. The cooperative role of immunity has been recently considered in atherosclerotic plaque inflammation, especially adaptive immune response by T cells. In this review, we examine the possible role of T cells in atherosclerosis-mediated inflammation and conceivable therapeutic strategies that can ameliorate complications of atherosclerosis. The cytokines secreted by T-lymphocyte subsets, different pathophysiological profiles of microRNAs (miRs), and the growth factor/receptor axis have diverse effects on the inflammatory cycle of atherosclerosis. Manipulation of miRNA expression and prominent growth factor receptors involved in inflammatory cytokine secretion in atherosclerosis can be considered diagnostic biomarkers in the induction of anergy and blockade of atherosclerotic development. This manuscript reviews immunomodulation of T cells responses in atherosclerosis anergy.
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http://dx.doi.org/10.1093/labmed/lmaa003DOI Listing
November 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 HLA-DRB1*11 group-specific allele is a predictor for alloantibody production in the transfusion-dependent thalassemia patients.

Transfus Apher Sci 2020 Jun 9;59(3):102729. Epub 2020 Jan 9.

Thalassemia & Hemoglobinopathy Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; Clinical Research Development Unit, Golestan Hospital, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. Electronic address:

Background And Objectives: Recently, researchers have shown an increased interest in thalassemia for detecting susceptible factors in alloimmunization development. Alloimmunization, especially against Rh and Kell blood, occurs in 30% of thalassemia dependent transfusion (TDT) patients. The aim of this study is to determine the role of HLA-DRB1*11 and HLA-DRB1*13 group-specific alleles in the production of Rh and Kell alloantibodies.

Materials And Methods: 106 TDT patients were recruited for this study (54 responders and 52 non-responders). Responder patients developed Rh, Kell and/or specificities alloantibodies. HLA genotyping was done with Sequence-Specific Primers (SSP-PCR) and the results were compared between two groups.

Results: A significant association was found between anti-K (P=0.021, OR=2.546, 95%CI) and anti-E (P=0.049, OR=2.304, 95%CI) alloantibodies production with DRB1*11, respectively. Development of Anti-K and Anti-E alloantibodies were associated with DRB1*11 (P = 0.021, OR = 2.546, 95%CI) (P = 0.049, OR = 2.304, 95%CI), respectively. Further analysis showed that DRB1*11 is more frequent in multi responders (responder with both Rh and Kell alloantibodies) than mono-responders, 71% Versus 29%. There was not found any association between the DRB1*13 group-specific allele and the production of alloantibodies (P = 0.584, OR = 0.308, 95%CI).

Conclusions: The evidence from this study suggests that detecting the DRB1*11 group-specific allele before starting transfusion can be useful to identify susceptible patients, increase HSCT transplantation compatibility and blood transfusion management.
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http://dx.doi.org/10.1016/j.transci.2020.102729DOI Listing
June 2020

STAT5: From Pathogenesis Mechanism to Therapeutic Approach in Acute Leukemia.

Lab Med 2020 Jul;51(4):345-351

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

Background: Based on the results of multiple studies, multiple signaling pathways is a major cause of resistence to chemotherapy in leukemia cells. Signal transducer and activator of transcription 5 (STAT5) is among these factors; it plays an essential role in proliferation of leukemic cells.

Methods: We obtained the materials used in our study via PubMed search from 1996 through 2019. The key search terms included "STAT5," "acute leukemia," "leukemogenesis," and "mutation."

Results: On activation, STAT5 not only inhibits apoptosis of leukemic cells via activating the B-cell lymphoma 2 (BCL-2) gene but also inhibits resistance to chemotherapy by enhancing human telomerase reverse transcriptase (hTERT) expression and maintaining telomere length in cells. It has also been shown that a number of mutations in the STAT5 gene and in related genes alter the expression of STAT5.

Conclusion: The identification of STAT5 and the factors activated in its up- or downstream expression, affecting its function, contribute to better treatments such as targeted therapy rather than chemotherapy, improving the quality of life patients.
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http://dx.doi.org/10.1093/labmed/lmz074DOI Listing
July 2020

Investigation of JAK2V617F Mutation Prevalence in Patients with Beta Thalassemia Major.

Lab Med 2020 Mar;51(2):176-180

Health Research Institute, Thalassemia & Hemoglobinopathy Research Center.

Background: Beta (β)-thalassemia major is a genetic disorder with anemia and an increased level of erythropoietin by Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathway. JAK plays an important role in cell signaling, and the common mutation in the JAK2 gene in myeloid disorders is called JAK2V617F.

Methods: A total of 75 patients with beta (β)-thalassemia major patients, including 34 males (45%) and 41 females (55%), were enrolled in this study. The presence of the JAK2V617F mutation was assessed using the amplification-refractory mutation-polymerase chain reaction (ARMS-PCR) technique.

Results: Among the 75 patients, 14 patients (19%) tested positive and 61 patients (81%) tested negative for JAK2V617F mutation. We observed no statistically significant difference in sex, age, genotype, and JAK2V617F mutation among patients (P> .05). However, a significant difference between blood-transfusion frequency and JAK2V617F mutation was observed (P <.05).

Conclusion: Due to the low prevalence of JAK2V617F mutation in thalassemia, using a larger population of the patients to investigate this mutation in ineffective erythropoiesis can be useful.
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http://dx.doi.org/10.1093/labmed/lmz045DOI Listing
March 2020

Prognostic significance of mutated genes in megakaryocytic disorders.

Oncol Rev 2019 Jul 22;13(2):408. Epub 2019 Jul 22.

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

Megakaryopoiesis is a process during which platelets that play a major role in hemostasis are produced due to differentiation and maturation of megakaryocytic precursors. Several genes, including oncogenes and tumor suppressor genes, play a role in the regulation of this process. This study was conducted to investigate the oncogenes and tumor suppressor genes as well as their mutations during the megakaryopoiesis process, which can lead to megakaryocytic disorders. Relevant literature was identified by a PubMed search (1998-2019) of English language papers using the terms ', and According to investigations, several mutations occur in the genes implicated in megakaryopoiesis, which abnormally induce or inhibit megakaryocyte production, differentiation, and maturation, leading to platelet disorders. GATA-1 is one of the important genes in megakaryopoiesis and its mutations can be considered among the factors involved in the incidence of these disorders. Considering the essential role of these genes (such as GATA- 1) in megakaryopoiesis and the involvement of their mutations in platelet disorders, study and examination of these changes can be a positive step in the diagnosis and prognosis of these diseases.
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http://dx.doi.org/10.4081/oncol.2019.408DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6661530PMC
July 2019

Expression of Blood Cells Associated CD Markers and Cardiovascular Diseases: Clinical Applications in Prognosis.

Lab Med 2020 Mar;51(2):122-142

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

Background: Cardiovascular diseases (CVDs) are a major cause of mortality worldwide. The results of various studies have shown that abnormality in the frequency and function of blood cells can be involved in CVD complications. In this review, we have focused on abnormalities in the expression of the CD (cluster of differentiation) markers of blood cells to assess the association of these abnormalities with CVD prognosis.

Methods: We identified the relevant literature through a PubMed search (1990-2018) of English-language articles using the terms "Cardiovascular diseases", "CD markers", "leukocytes", "platelets", and "endothelial cells".

Results: There is a variety of mechanisms for the effect of CD-marker expressions on CVDs prognosis, ranging from proinflammatory processes to dysfunctional effects in blood cells.

Conclusion: Considering the possible effects of CD-marker expression on CVDs prognosis, particularly prognosis of acute myocardial infarction and atherosclerosis, long-term studies in large cohorts are required to identify the prognostic value of CD markers and to target them with appropriate therapeutic agents.
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http://dx.doi.org/10.1093/labmed/lmz049DOI Listing
March 2020

Microarray analysis of apoptosis gene expression in liver injury induced by chronic exposure to arsenic and high-fat diet in male mice.

Environ Sci Pollut Res Int 2019 Sep 9;26(25):26351-26366. Epub 2019 Jul 9.

Department of Pharmacology and Toxicology, School of Pharmacy, Ahvaz Jundishpur University of Medical Sciences, Ahvaz, Iran.

Rapid growth in the incidence of liver disease is largely attributable to lifestyle and environmental contaminants, which are often overlooked as the leading causes of this problem. Thus, the possible contribution of arsenic (As) to high-fat diet (HFD)-induced liver damage was examined via microarray analysis. To perform this experiment, a total number of 40 healthy adult male NMRI mice (22-30 g) were used. To this end, these animals were randomly assigned to four groups of 10. Oxidative stress and histopathological parameters were also evaluated in the liver of the mice exposed to a minimally cytotoxic concentration of As (50 ppm) in drinking water while being fed with a HFD for 20 weeks. Subsequently, apoptosis gene expression profiling was utilized via real-time (RT) PCR array analysis. The results showed that As had increased the amount of HFD-induced liver damage and consequently amplified changes in oxidative stress factors, histopathological parameters, as well as apoptosis pathway genes. Investigating the expression profile of apoptosis pathway genes similarly revealed that caspase-8, as a main upstream contributor to the apoptosis pathway, might play an important role in the induction of apoptosis generated by As and HFD. Ultimately, this study highlighted that As in drinking water could increase sensitivity in mice to HFD-induced liver disease through strengthening apoptosis pathway.
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http://dx.doi.org/10.1007/s11356-019-05907-3DOI Listing
September 2019

Platelets in In-stent Restenosis: From Fundamental Role to Possible Prognostic Application.

Curr Cardiol Rev 2020 ;16(4):285-291

Thalassemia & Hemoglobinopathy Research center, Health research institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

Background: Introduction of new generations of stents has decreased the percentage of patients experiencing in-stent restenosis (ISR) following the implantation of stent. However, a large number of patients are still afflicted with this phenomenon, which necessitates further study of ISR pathophysiology.

Methods: Relevant English literature was searched up to 2018 and retrieved form the PubMed database and Google Scholar search engine. The following keywords were used: "In-stent restenosis", "Platelet", "Chemokine", "Inflammation", "Vascular smooth muscle cell" and "Neointima".

Results: Previous studies have shown that ISR is a pathophysiologic response to damage of the artery wall after its elongation and separation of the atherosclerotic plaque. Development of neointimal hyperplasia (NIH) following this pathophysiologic response is a function of inflammation caused by platelets, monocytes, macrophages, and lymphocytes, as well as rapid migration and proliferation of generally quiescent cells in the median layer of the artery wall.

Conclusion: After damage to the artery wall, platelets play an essential role in the incidence of NIH by contributing to inflammation and migration of vascular smooth muscle cells and extracellular matrix remodeling, especially via secretion of different chemokines; therefore, developing therapeutic strategies for platelet inhibition in a controlled manner could be the basis of preventive treatments in the near future. In this study, for the first time, we hypothesize that evaluation of platelet activity profile in patients before and after stent implantation may determine the prognosis and likelihood of ISR.
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http://dx.doi.org/10.2174/1573403X15666190620141129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903513PMC
February 2021

HLA-B5, 7, 8, 27, and 51 Antigens and Immune Thrombocytopenic Purpura: Is There an Association?

J Pediatr Hematol Oncol 2020 01;42(1):e32-e37

Thalassemia & Hemoglobinopathy Research Center, Health Research Institute.

Background: Immune thrombocytopenic purpura (ITP) is a bleeding disorder characterized by low platelet counts in peripheral blood, impairment of thrombopoiesis in bone marrow, and risk of mild to severe bleedings. ITP can be seen among both sexes in different ages. Although definitive pathogenesis of this disorder is still ambiguous, some of risk factors for ITP are recognized, including human leukocyte antigens (HLAs).

Objective: Our goal was to evaluate the possible association between HLA-B5, 7, 8, 27, and 51 antigens with ITP for the first time. We were hoping to achieve new hypothetical diagnostic/prognostic biomarkers to introduce a new subject for further studies on HLA class I antigens as possible risk factors for ITP.

Materials And Methods: A total of 37 patients with ITP were included in this study. After confirmation of ITP diagnosis, peripheral blood samples were collected from them. The expression of each of HLA antigens was evaluated by standard lymphocytotoxicity technique.

Results: Compared with other studied antigens, the expression of HLA-B5 and HLA-B51 was more prevalent among our patients. According to the results, 22% of patients were positive for HLA-B5 and HLA-B51. Furthermore, no significant association was found between HLAs expressions with complete blood count parameters.

Conclusions: We conclude that there is an association between HLA-B5 and HLA-B51 with ITP and that they are not likely to be used as diagnostic or prognostic biomarkers. We suggest studying the association between HLA-B antigens and ITP in large-scale studies to determine whether or not there is a significant association.
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http://dx.doi.org/10.1097/MPH.0000000000001543DOI Listing
January 2020

Neutropenia and leukemia development: genetic risk factors and prognosis.

Leuk Lymphoma 2019 12 19;60(14):3363-3374. Epub 2019 Jun 19.

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

Neutropenia is known as a clinical consequence in various genetic disorders and other neutropenia-inducing mutations (NIM) nonmalignant diseases. Leukemia development is now a major concern about the mortality of patients with congenital neutropenia. We searched the PubMed database and Google Scholar engine using English-language article (1980-2019) using the terms 'Neutropenia,' 'Leukemia,' 'Mutation,' and 'Polymorphism.' Patients with neutropenia have leukemia-related genetic abnormalities which are noticeable as mutations and chromosome abnormalities. The presence of mutations in patients with neutropenia can affect the biological function of neutrophils and increase the likelihood of leukemia progression, which can be important in the diagnosis and prognosis of patients. NIM can play an important role in leukemia development via enhancing intracellular signaling, apoptosis inhibition, and effects on transcription factors in patients with neutropenia. Therefore, the detection of genetic risk factors can be useful in prognosis, early diagnosis, and prevention of leukemia development.
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http://dx.doi.org/10.1080/10428194.2019.1630622DOI Listing
December 2019

Evaluation of complete blood count parameters in cardiovascular diseases: An early indicator of prognosis?

Exp Mol Pathol 2019 10 11;110:104267. Epub 2019 Jun 11.

Thalassemia & Hemoglobinopathy Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. Electronic address:

Background: Studies have been conducted to evaluate the correlation between complete blood count (CBC) indices and cardiovascular diseases (CVDs). Considering the dispersion of these studies as well as reports on prognostic value of CBC parameters in CVDs, we have summarized these findings as a review article for the first time.

Methods: Relevant English language literature was searched and retrieved from Google Scholar search engine and PubMed database (1996-2018). We used "Complete blood count", "Cardiovascular disease", "Red cell distribution width", and "Mean platelet volume" as keywords.

Results: Numerous studies indicated that red cell distribution width (RDW) is an independent prognostic biomarker in relation to CVD diseases. MPV is another considerable prognostic biomarker for CVDs. Elevations of inflammatory markers such as neutrophil to lymphocyte ratio (NLR) in CVD patients (especially in myocardial infarction and heart failure) can be considered as a factor of poor prognosis.

Conclusions: RDW can be used as a valuable independent biomarker to investigate the prognosis of patients with heart failure (HF), atherosclerosis, myocardial infarction (MI), and other CVDs. Rapid and stable increase in MPV makes it a reliable prognostic/diagnostic parameter in CVDs such as MI and unstable angina. Among different inflammatory markers the evaluation of total white blood cell count, NLR, monocyte to high-density lipoprotein ratio (MHR) and platelet to lymphocyte ratio (PLR) may have a high value in predicting the prognosis of different CVDs including MI, HF and atherosclerosis in patients.
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http://dx.doi.org/10.1016/j.yexmp.2019.104267DOI Listing
October 2019

Involvement of circulating inflammatory factors in prognosis and risk of cardiovascular disease.

J Mol Cell Cardiol 2019 07 15;132:110-119. Epub 2019 May 15.

Thalassemia & Hemoglobinopathy Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. Electronic address:

Cardiovascular disease (CVD) is an inflammatory disease that different factors play a crucial role in the development of clinical outcome of this disease. Inflammation could have effects on initiation, progression, and clinical complications of CVD. Previous studies have indicated that delineating the underlying mechanisms of inflammatory factors involved in this disease should be considerably beneficial both as predictive markers and targets for advancement of appropriate therapeutic approaches in offsetting development and progression of cardiovascular complications. Mechanisms of inflammatory factors involved in CVD combined with the development of atherosclerosis, reperfusion injury, and myocardial infarction caused by changes in processes such as endothelial cells function and hemostasis can contribute to the development of clinical outcome in CVD. Therefore, it can be stated that recognition of inflammatory mechanisms involved in this disease can be a promising tool for evaluation of prognosis in CVD patients. In this article, our goal is to evaluate the possible role of changes in the expressions of inflammatory factors in CVD as well as their relationship with prognosis of this disease.
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http://dx.doi.org/10.1016/j.yjmcc.2019.05.010DOI Listing
July 2019

CD markers variations in chronic lymphocytic leukemia: New insights into prognosis.

J Cell Physiol 2019 11 2;234(11):19420-19439. Epub 2019 May 2.

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

Chronic lymphocytic leukemia (CLL) is one of the most commonly occurring adult leukemias that is associated with clonal accumulation of mature apoptosis-resistant B-cells in bone marrow, peripheral blood, and specific tissues. Different pathogenesis factors can contribute to the aggression of the clinical course in this disease. Cytogenetic abnormalities and surface biomarkers of neoplastic CLL cells can be effective in the outcome of CLL, and the examination of changing CD markers expressions in the progression of CLL can be related to the prognosis of this disease. Changing expression levels of CD markers on lymphocytes and other cells in CLL patients can play a role in the aggressive clinical outcomes such as organomegaly, immunodeficiency, and advanced disease stages through their interaction with CLL microenvironment. Given the involvement of CD markers in the pathogenesis of CLL, it can be stated that recognizing the expression changes of CD markers in the cells involved in CLL can be a proper approach to evaluate prognosis among these patients.
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http://dx.doi.org/10.1002/jcp.28724DOI Listing
November 2019