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

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.

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

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.

Role of bone marrow adipocytes in leukemia and chemotherapy challenges.

Adipose tissue (AT) is an extramedullary reservoir of normal hematopoietic stem cells (HSCs). Adipocytes prevent the production of normal HSCs via secretion of inflammatory factors, and adipocyte-derived free fatty acids may contribute to the development and progression of leukemia via providing energy for leukemic cells. In addition, adipocytes are able to metabolize and inactivate therapeutic agents, reducing the concentrations of active drugs in adipocyte-rich microenvironments. The aim of this study was to detect the role of adipocytes in the progression and treatment of leukemia. Relevant literature was identified through a PubMed search (2000-2018) of English-language papers using the following terms: leukemia, adipocyte, leukemic stem cell, chemotherapy, and bone marrow. Findings suggest the striking interplay between leukemic cells and adipocytes to create a unique microenvironment supporting the metabolic demands and survival of leukemic cells. Based on these findings, targeting lipid metabolism of leukemic cells and adipocytes in combination with standard therapeutic agents might present novel treatment options.

Clonal hematopoiesis: Genes and underlying mechanisms in cardiovascular disease development.

The clonal hematopoiesis when occurring without hematologic abnormalities is defined as clonal hematopoiesis of indeterminate potential (CHIP). Aging causes accumulation of somatic mutations, and hematopoietic stem cells (HSCs) can develop clonal expansion of different lineages by these mutations. CHIP has a correlation with cancer and cardiovascular disease (CVD) through acquired mutations in genes. DNMT3A, TET2, ASXL1, and JAK2 genes as well as other genes are the most common somatic mutations causing CHIP and CVD in an older age. Other factors such as cholesterol level, laboratory tests and indexes also affect CVD. In addition, mutations in adenosine triphosphate-binding cassette transporters and also chronic stress in nervous system can result in HSCs proliferation and CVD. However, laboratory tests and indexes are not sensitive for CVD diagnosis. But the therapeutic interventions can be helpful to prevent CVD cases by targeting somatic mutations, chemokine receptors, and growth factors in HSCs. Also, new drugs can control CVD by targeting of cells and their signaling pathways in HSCs. Therefore, more investigations are needed and more questions should be answered for the relationship between CHIP and CVD as a challenging issue in future.

Singe nucleotide polymorphisms in osteosarcoma: Pathogenic effect and prognostic significance.

PURPOSE: Osteosarcoma (OS) is a common malignant bone tumor in children and adolescents. Pathogenesis and prognosis of OS can be associated with several environmental and genetic factors. Single nucleotide polymorphisms (SNPs) are crucial genetic changes that can be involved in clinical and therapeutic outcomes of OS. The aim of this review is to present a synopsis of the role of SNPs in pathogenesis and prognosis of OS tumor cells as well as their potential as therapeutic targets to improve the outcomes of patients. METHOD: The content used in this paper has been obtained by an electronic databases search of English language (1998-2018) articles using the terms "Single nucleotide polymorphisms", "Osteosarcoma", "Pathogenesis", "Prognosis", and "Clinical Outcomes". DISCUSSION: SNPs can affect a number of biological processes such as proliferation, apoptosis, adhesion, invasion, and drug resistance of OS tumor cells, playing a key role in pathogenesis, prognosis, and clinical outcomes after chemotherapy in this disease. CONCLUSION: Considering the importance of SNPs in OS pathophysiology, these genetic changes may be used as potential pathogenic and prognostic biomarkers for OS. It is hoped that targeting these changes using new therapeutic approaches leads to the effective treatment of this debilitating tumor. However, better understanding of OS biology and further clinical trials are needed to achieve this goal.

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

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.

CD markers polymorphisms as prognostic biomarkers in hematological malignancies.

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.

The Relation between Different Aspects of Quality of Life with Coping Style in Adolescents with Thalassemia in Comparison to a Healthy Group.

Background: Thalassemia as a chronic disease could affect different aspects of a patient's life. On the other hand, when encountering the symptoms of a chronic disease as a stressful factor, the coping strategy of the adolescents and their families could have an important role in the quality of life of these patients. The present study was conducted to determine the relation between different aspects of quality of life with coping styles in the adolescents with thalassemia in comparison to a healthy control group. Materials and Methods: The present study is a case-control research in 2017. Studied samples were 200 adolescents with thalassemia and healthy adolescents. Data gathering tools were demographic characteristics checklist and the coping style and quality of life questionnaire by the World Health Organization. Data were analyzed by SPSS 20 using independent t-test, linear regression and correlation coefficients. Conclusion: Results of Pearson statistical test showed a positive and significant relation between the total mean score of quality of life and its physical, social and mental aspects with emotion-oriented coping style (p<0.01). Also a direct significant relation was observed between the total mean score of quality of life and its social and physical aspects with problem-oriented coping style(p<0.01). Conclusion: According to the results of the present study, educating the adolescents and their families for paying attention to the coping style for stressful factors and preparing these adolescents for passing toward the youth period, which could be challenging for them, are highly recommended.

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

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.

Thrombocytopenia in solid tumors: Prognostic significance.

Solid tumors are a heterogeneous group of malignancies that result from out-of-control proliferation of cells. Thrombocytopenia is a common complication among patients with solid tumors that predispose them to bleeding disorders. The aim of this review article is to investigate the underlying mechanisms of the risk and incidence of thrombocytopenia in solid tumors. It can be argued that thrombocytopenia is a poor prognostic factor in solid tumors that can result from several factors such as polymorphism and mutation in some transcription factors and cytokines involved in megakaryocytic maturation or from the adverse effects of treatment. Therefore, an understanding of the exact mechanism of thrombocytopenia pathogenesis in each stage of solid tumors can help in developing therapeutic strategies to decrease bleeding complications in these malignancies.

Prognostic significance of aberrant CD5 expression in B-cell leukemia.

Aberrant expression of CD5 (as a T-cell marker) is seen in some leukemia and lymphoma of B lineage origin. Given that the signaling resulting from the expression of this marker plays an essential role in the development of leukemia and lymphoma, evaluating the expression of this marker is of paramount importance. Therefore, our goal in this study was to investigate the prognostic importance of CD5 expression in B-cell leukemia and lymphoma. We evaluate CD5 expression in normal and leukemic B-cells by identifying relevant literature through a PubMed search (1998-2018) of English language papers using the terms: 'CD5,' 'B-cell,' 'Leukemia,' and 'Lymphoma.' We are doing this thorough comparison of results from CD5 positive and negative cases to make a correct decision about prognostic importance of CD5 expression in these malignancies. In a number of B-cell malignancies, CD5 is expressed in varying degrees. Due to the different origins and characteristics of these malignancies, the results of CD5 expression evaluations are heterogeneous and impossible to generalize. However, CD5 expression is sometimes associated with clinicopathologic findings, more invasive clinical course, and even resistance to treatment (specifically in DLBCL) among CD5- positive patients, which appears to be a function of CD5 signaling and its downstream factors such as STAT3. Depending on the type of malignancy, CD5 expression is associated with good or bad prognosis, which can be used as an auxiliary prognostic factor to assess the clinical course of B-cell malignancies. Moreover, the difference in expression levels of CD5 in a variety of B-cell malignancies allows for differential diagnosis of these malignancies, which can be helpful when diagnosis is difficult.

Vitamin D deficiency in patients with Behcet's disease.

BACKGROUND: Behcet's disease is an autoimmune, recurrent and multisystem disease. Vitamin D has immunomodulator role in immune system. So that vitamin D deficiency was reported in some autoimmune diseases. Behcet's disease as a Silk Road disease is common in Iran. The aim of this study was to detect the serum level of 25(OH) vitamin D in Behcet's patients and control group. METHODS: In this case-control study, 112 Behcet's patients as cases group and 112 healthy individuals as controls group were enrolled. Any subject on vitamin D supplement, steroid, and immunosuppressors during the last 6 months were excluded. The serum level of 25(OH) vitamin D was measured in the two groups by ELISA method. The findings were compared via SPSS software. RESULTS: About 57% and 17% of Behcet's patients had vitamin D deficiency and insufficiency respectively. Vitamin D deficiency was significantly more common in controls than cases group (P < 0.001). Vitamin D levels were significantly lower in controls (P < 0.001). Age and sex did not have any confounding effect on the results. There was no significant relationship between disease duration, disease activity, Pathergy test, HLA-B5, and HLA-B51 with vitamin D level in Behcet's patients. CONCLUSIONS: Vitamin D deficiency is common among Behcet's patients. However, our results revealed vitamin D deficiency was significantly more common in healthy controls in comparison with Behcet's cases.

Asymtomatic essential thrombocythemia in a child: a rare case report.

Essential thrombocythemia is a rare myeloproliferative disorder in pediatrics. This myeloproliferative disorder is charactherized by thrombocytosis and hyperplasia of megakaryocytes in the bone marrow. Other cell lines are not involved. JAK2V617F mutation has been identified in approximately half the patients with this disorder. We describe a 12-year-old boy with essential throbocythemia. The patient had a persistent thrombocytosis over 600x10(9) /L and the time of diagnosis, his platelet count ranged between 900x10(9)and 2150x10(9)/L. Megakaryocytes in the bone marrow were increased in number. The chromosomal analysis was normal and bcr/abl rearrangement was negative. He remained asymptomatic throughout the follow-up period.