Effect of a partnership care programme on quality of life in school-age children with leukaemia: a controlled clinical trial.

Background: Despite the low quality of life (QoL) of children with leukaemia, there is a lack of well-designed and culture-oriented care programmes to improve it. The Partnership Care Model (PCM), which was developed based on the Iranian culture, seems to be effective in improving the QoL in children living with chronic diseases. Aim: This study aimed to evaluate the effect of a care programme based on the PCM on the QoL of children with leukaemia. Methods: This controlled clinical trial encompassed 60 school-age children with leukaemia and their mothers. In the experimental group (n=30), a 2-month care programme was implemented based on the PCM, including the four stages of motivation, preparation, involvement and evaluation. Only standard care was provided to the control group (n=30). Children's QoL was assessed using the Paediatric Quality of Life Inventory 3.0 Cancer Module in the pre-test phase and 2 months after the intervention. Findings: The total score of QoL and all its subscales were significantly higher in the experimental group than the control group in the post-test phase (p<0.001). Moreover, a significant difference was observed between pre-test and post-test scores in all domains in the experimental group (p<0.001); however, no significant difference was noticed between the scores in the control group. Conclusion: The partnership care programme seems to improve the QoL in children with leukaemia. Future investigations are recommended to shed further light on the findings of this study.

COVID-19 in a case with Kikuchi-Fujimoto disease.

The accurate diagnosis of Kikuchi-Fujimoto disease can protect children from unnecessary diagnostic procedures and treatments. Also, the co-occurrence of rare diseases with other diseases can improve or worsen the symptoms of the patients.

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

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.

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.

Involvement of Interferon-γ + 874A/T Polymorphism in the Pathogenesis of and Therapeutic Response to Immune Thrombocytopenia.

BACKGROUND: Immune thrombocytopenia (ITP) is an autoimmune disease characterized by symptoms of thrombocytopenia and bleeding due to production of autoantibodies against platelets. Recently, the occurrence of polymorphisms has been identified as one of the main causes of disease onset. METHODS: To conduct this study, we recruited 140 patients and control individuals with no history of platelet loss. After collection of specimens, the prevalence of interferon-γ polymorphism was evaluated using the allele-specific oligonucleotide-polymerase chain reaction (ASO-PCR) technique and confirmed by sequencing techniques. RESULTS: The results showed that the frequency of the AA genotype was higher in the control group, compared with patients with ITP; however, in the acute and chronic groups, the frequency of the AT genotype was higher than that of the AA genotype. We also discovered that there was no significant correlation between platelet counts before and after treatment, nor in its related parameters with interferon (IFN)-γ polymorphism. CONCLUSION: rs2430561 does not seem to have any role in ITP pathogenesis and treatment response.

The Association Between Human Leukocyte Antigens and ITP, TTP, and HIT.

BACKGROUND: Autoimmune thrombocytopenia in immune thrombocytopenic purpura (ITP), thrombotic thrombocytopenic purpura (TTP), and heparin-induced thrombocytopenia (HIT) is associated with immunologic degradation of platelets and reduced platelet counts in patients, leading to bleeding risk in patients. Considering the role of human leukocyte antigens (HLA) in the development of immune response, in this review, we examine the relationship between HLA and pathogenesis of the above-mentioned diseases. METHODS: Relevant English-language literature was searched and retrieved from Google Scholar search engine and PubMed database (1979 to 2018). The following keywords were used: "Immune Thrombocytopenic purpura," "Thrombotic Thrombocytopenic Purpura," Human Leukocyte Antigen," and "Heparin-induced thrombocytopenia." RESULTS: In autoimmune thrombocytopenia, HLA molecule presents self-antigens or foreign antigens similar to self-antigens, provoking an immune response against platelets that results in the degradation of platelets in peripheral blood and possible bleeding in the patient. For example, HLA-DRB1 *11 presents the self-antigen and induces an immune response against ADAMTS13, which is associated with thrombocytopenia in TTP patients. CONCLUSIONS: HLA alleles can be used as prognostic biomarkers for immunologic disorders of platelet such as ITP, TTP, and HIT. Different DRB1 alleles enable the assessment of resistance to common ITP treatments as well as disease prognosis. Due to the genetic association between HLA-DR1 and HLA-DQ1 alleles and the role of HLA-DRB1 *11 in TTP, the HLA-DQB1 *02: 02 allele may also play a role in TTP pathogenesis.

Cellular expression of CD markers in immune thrombocytopenic purpura: implications for prognosis.

Immune thrombocytopenic purpura (ITP) is an autoimmune bleeding disorder associated with platelet destruction. Abnormalities in frequency and function of different immune cells can play a crucial role in this disease. The aim of this study was to evaluate the prognostic value of CD markers' expressions by immune cells in ITP. Peripheral blood samples were collected from 25 ITP patients before and after treatment. The expression of CD markers was evaluated by flow cytometry technique. The expression of CD38 and CD56 was significantly lower before treatment than after it (p = 0.025 and p = 0.036, respectively). Furthermore, a positive correlation was found between CD38 expression with platelet count before (r = 0.496, p = 0.012) and after treatment (r = 0.404, p = 0.045). No significant relationship was found between this marker and platelet count while CD4 expression was higher before treatment than after it (p = 0.002). In conclusion, CD38 may have independent prognostic value in ITP and we suggest that it can be a prognostic marker for this disease.

Aberrant DNA Methylation in Chronic Myeloid Leukemia: Cell Fate Control, Prognosis, and Therapeutic Response.

Chronic myeloid leukemia (CML) is a hematopoietic stem cell malignancy characterized by the expression of the BCR-ABL1 fusion gene with different chimeric transcripts. Despite the crucial impact of constitutively active tyrosine kinase in CML pathogenesis, aberrant DNA methylation of certain genes plays an important role in disease progression and the development of drug resistance. This article reviews recent findings relevant to the effect of DNA methylation pattern of regulatory genes on various cellular activities such as cell proliferation and survival, as well as cell-signaling molecules in CML. These data might contribute to defining the role of aberrant DNA methylation in disease initiation and progression. However, further studies are needed on the validation of specific aberrant methylation markers regarding the prognosis and prediction of response among the CML patients.

Thrombocytopenia in leukemia: Pathogenesis and prognosis.

Leukemias, a heterogeneous group of hematological disorders, are characterized by ineffective hematopoiesis and morphologic abnormalities of hematopoietic cells. Thrombocytopenia is a common problem among leukemia types that can lead to hemorrhagic complications in patients. The purpose of this review article is to identify the conditions associated with the incidence of thrombocytopenia in leukemias. It can be stated that although translocations have been considered responsible for this complication in many studies, other factors such as bone marrow failure, genes polymorphism, a mutation in some transcription factors, and the adverse effects of treatment could be associated with pathogenesis and poor prognosis of thrombocytopenia in leukemias. Considering the importance of thrombocytopenia in leukemias, it is hoped that the recognition of risk factors increasing the incidence of this complication in leukemic patients would be useful for prevention and treatment of this disorder.

Expression of CD markers' in immune thrombocytopenic purpura: prognostic approaches.

Immune Thrombocytopenic Purpura (ITP) is a common autoimmune bleeding disorder characterized by a reduction in peripheral blood platelet counts. In this disease, autoantibodies (Auto-Abs) are produced against platelet GPIIb/GPIIIa by B cells, which require interaction with T cells. In this review, the importance of B and T lymphocytes in ITP prognosis has been studied. Relevant literature was identified by a PubMed search (1990-2016) of English-language papers using the terms B and T lymphocyte, platelet, CD markers and immune thrombocytopenic purpura. T and B lymphocytes are the main immune cells in the body. Defective function causes disrupted balance of different subgroups of lymphocytes, and abnormal expression of surface markers of these cells results in self-tolerance dysfunction, as well as induction of Auto-Abs against platelet glycoproteins (PG). Given the role of B and T cells in production of autoantibodies against PG, it can be stated that the detection of changes in CD markers' expression in these cells can be a good approach for assessing prognosis in ITP patients.

Association between gene polymorphisms and clinical features in idiopathic thrombocytopenic purpura patients.

: Immune thrombocytopenic purpura (ITP) is an autoimmune disease in which increased platelet destruction and thrombocytopenia are diagnostic features. In fact, the exact pathogenesis of this disease is still unknown, but genetic changes can be a potential factor in the development of ITP. In this study, the relationship between polymorphisms with platelet destruction has been studied, which leads to decreased platelet count. Relevant literature was identified by a PubMed search (2000-2016) of English language papers using the terms 'ITP', 'polymorphism,' and 'immune system'. The majority of genetic changes (polymorphisms) occur in immune system genes, including interferon (IFN)-γ gene. These changes lead to the dysfunction of immune system and production of pathogenic antibodies against platelet surface glycoproteins such as glycoprotein IIb/IIIa, which eventually result in the destruction of platelets and increasing disease severity. In addition, IFN-γ as well as factors and cytokines involved in megakaryopoiesis, including stem cell factor and interleukin-3 (IL-3), leads to the differentiation of megakaryocytes and platelet release. Considering the fact that IFN-γ is a factor of inflammation and thrombocytopenia, coexistence of this cytokine with thrombopoietin, stem cell factor, and IL-3 results in megakaryocytes differentiation and platelet production, which can be effective to reduce disease severity and increase the platelet counts.

The Influence of Polymorphisms in Disease Severity in ß-Thalassemia.

ß-Thalassemia is a genetic disorder with a continuum of mild to severe clinical manifestations and requirement of transfusion at different stages of life. The cause(s) of this variety is not clear but genetic alterations could be a potential factor. In this review, the correlation between polymorphisms and different clinical manifestations, including the need for transfusion, was investigated. Relevant articles published in pubmed database from 1982 onwards were studied and compiled. The articles all contained the keywords ß-thalassemia, genetic modifiers, and mutations. Certain polymorphisms and mutations could dictate the severity of symptoms as well as their onset. A significant number of the mentioned genetic alterations appear in beta-globin gene cluster and affect gamma chain. Therefore, hemoglobin F production rate is increased and can affect thalassemia symptoms and can relieve ß-thalassemia symptoms. A number of polymorphisms in catalase and glutathione S transferase genes have also been shown to modify the severity of disease and response to treatment. Knowledge of these mutations and polymorphisms can provide an insight into the prognosis for individual patients, especially in young ages or before birth to take proper measures in advance and eventually ameliorate the symptoms in the long run.

Regulatory effect of chemokines in bone marrow niche.

Chemokines secreted from different cellular components of bone marrow (BM) play an important role in the formation of the BM niche system. The hematopoietic stem cell (HSC) pool located in specialized anatomical sites within the BM is subjected to a complex network of chemokines, such that the produced chemokines affect the fate of these cells. Expression of different chemokine receptors on leukemic stem cells (LSCs) uncovers the critical role of chemokines in the maintenance, survival and fate of these cells in the leukemic niche. As a pre-metastatic niche rich in a variety of chemokines, the BM niche is turned into a locus of tumor cell development and division. The chemokine receptors expressed on the surface of metastatic cells lead to their metastasis and homing to the BM niche. Knowledge of chemokines and their receptors leads to the production of various therapeutic antagonists at chemokine receptors expressed on leukemic and tumor cells, enabling interference with chemokine function as a therapeutic tool. New findings suggest that miRNAs, with their specific inhibitory function, affect the ability of producing and expressing chemokines and chemokine receptors. This review focuses on the emerging role of chemokines and their receptors in normal and pathologic conditions of the BM niche, and also discusses the new therapeutic methods with this background.

The role of notch signaling in bone marrow niche.

OBJECTIVE: Bone marrow (BM) niche is a three-dimensional structure composed of a series of cells and it is one of the most controversial topics in hematological malignancies, leukemia, and even metastasis. Here, we review the relationship between Notch signaling and different fates of stem cells and other BM niche cells. METHODS: Relevant English-language literature were searched and retrieved from PubMed (2000-2013) using the terms Notch signaling, BM niche, and microRNAs (miRNAs). DISCUSSION: Notch signaling pathway is a signaling system involved in cellular processes such as proliferation, differentiation, and apoptosis. The notch signaling pathway components are associated with interaction between leukemic, metastatic, and normal cells and their microenvironment. miRNAs play an important role in expression and regulation of signaling molecules. It is necessary to evaluate the relationship between aberrant miRNA expression and notch signaling such as miR-128 and miR-30 in glioma and angiogenesis with notch signaling, respectively. CONCLUSIONS: Characterizing malignant cells and future studies focus on better understanding the variety of cancers and apoptosis with activated Notch signaling pathway, may remain promising this signaling system as a safe and effective therapeutic target.

Frequency of beta-thalassemia or beta-hemoglobinopathy carriers simultaneously affected with alpha-thalassemia in Iran.

BACKGROUND: Beta-thalassemias are prevalent heritable single gene disorders affecting the quantity of the hemoglobin molecule. Rarely, a co-inheritance of these impairments with alpha-thalassemia and/or a hemoglobinopathy occurs and makes an important double heterozygote or homozygous state. Thus finding these cases is essential for genetic counseling. The present study aimed to identify the prevalence of coexistent alpha-thalassemia mutations, hemoglobinopathies, and beta-thalassemia determinants. METHODS: This descriptive study was performed on 5760 patients. We used complete blood cell count, Hb electrophoresis, and HbA2 measurement for thalassemia carrier identification. Increased HbA2 (> or = 3.5%) is the standard diagnostic marker for beta-thalassemia, while normal HbA2 with low MCH and MCV can indicate an alpha-thalassemia carrier or atypical beta-thalassemia minor. Individuals with MCV < 80 fL, MCH < 27 pg, and hemoglobin < or = 15.3 g/dL in men or < or = 14 g/dL in women, were candidates for molecular thalassemia investigations. Patients with abnormal hemoglobin varieties in hemoglobin electrophoresis were referred to a genetics laboratory for hemoglobinopathy detection. RESULTS: 141 subjects out of 5760 were affected by alpha and beta-thalassemia or a beta-hemoglobinopathy simultaneously, including: 13 (11.1%) fetuses, 55 (38.2%) male cases, and 73 (50.7%) females. Among these 141 alpha-thalassemia patients, 92 cases (65.24%) were beta-thalassemia carriers and 3 (2.12%) were beta-thalassemia major, 43(30.49%) had beta-hemoglobinopathies, and 3 cases (2.12%) had co-inherited beta-thalassemia and variant hemoglobins. 31 beta-gene mutations were observed in this population, the most common being HbS Cd6 (A > T) (24%). These thalassemia determinants account for about 46% of all detected mutations. As for alpha-gene mutations, -3.7 detection was the most prevalent. CONCLUSIONS: The relatively high prevalence of co-inherited alpha-thalassemia and hemoglobinopathies among beta-thalassemia carriers indicates the importance of molecular analysis to diagnose these double heterozygous or sole homozygous cases for prenatal diagnostic purposes and putting forth strategies to prevent more complicated and dangerous combinations.

BRAF Mutation in Hairy Cell Leukemia.

BRAF is a serine/threonine kinase with a regulatory role in the mitogen-activated protein kinase (MAPK) signaling pathway. A mutation in the RAF gene, especially in BRAF protein, leads to an increased stimulation of this cascade, causing uncontrolled cell division and development of malignancy. Several mutations have been observed in the gene coding for this protein in a variety of human malignancies, including hairy cell leukemia (HCL). BRAF V600E is the most common mutation reported in exon15 of BRAF, which is observed in almost all cases of classic HCL, but it is negative in other B-cell malignancies, including the HCL variant. Therefore it can be used as a marker to differentiate between these B-cell disorders. We also discuss the interaction between miRNAs and signaling pathways, including MAPK, in HCL. When this mutation is present, the use of BRAF protein inhibitors may represent an effective treatment. In this review we have evaluated the role of the mutation of the BRAF gene in the pathogenesis and progression of HCL.

Immune Thrombocytopenic Purpura in Children and Adults: A Comparative Retrospective Study in IRAN.

BACKGROUND: Immune thrombocytopenic purpura (ITP) is an autoimmune disease that can cause bleeding disorders in patients, and presents in acute and chronic forms. The acute form is frequently seen in children, but the chronic form mainly inflicts adults. There are differences and similarities in clinical and laboratory findings of the disease between children and adults. We study these differences and similarities in these two groups of patients with ITP. METHODS: In this study, we retrospectively evaluated the clinical and laboratory data of 323 ITP cases within three years. None of our patients had a history of thrombocytopenia. Patients were classified into two groups of children (3 months to 16 years of age) and adults (≥ 16 years). Data analysis was conducted using SPSS software, and the analysis results were compared between the two age groups. RESULTS: Overall, the disease prevalence was higher in women than men, but the prevalence of childhood ITP was higher in males than females. The prevalence of initial symptoms including petechiae, purpura and ecchymosis was 60.5% and 61%, respectively in all patients, but severe bleeding rarely occurred in patients (28.8%). 30.5% of patients had a history of infection before developing ITP, and the children had a higher frequency of infection (80.8%). Before treatment, the mean platelet count in adults and children was 33000/µL and 35000/µL, respectively. CONCLUSION: Comparison of data in children and adults with ITP indicated similarities and differences in clinical and laboratory findings between the two groups with differences in prevalence, bleeding symptoms, initial platelet count and infection history.

The role of the nervous system in hematopoietic stem cell mobilization.

Hematopoietic stem cells (HSCs) and blood cell progenitors, such as maturing leucocytes, steadily enter from bone marrow (BM) into the circulation under steady-state conditions, and their mobilization is dramatically amplified during stress conditions and by mediators such as granulocyte colony-stimulating factor (G-CSF). This mobilization is dependent upon bone remodeling, the proteolytic enzymes of bone marrow-derived stromal cells, and adhesion molecules such as integrin, but the main mechanisms controlling this traffic are still unclear. The nervous system, as the most important regulator of the body, can affect the mobilization network by secreting catecholamines, so that denervation of catecholaminergic fibers in the BM of mice could lead to declining mobilization in steady state and stress situations, even in the presence of other intact environmental factors in the BM. Thus, due to the importance of the nervous system, we have attempted to give a general overview of how the nervous system is involved in the mobilization of HSCs in this review. Then, we will try to describe the mobilization process induced by the nervous system, which consists of 3 mechanisms: stromal cell-derived factor 1 (SDF-1)/CXC chemokine receptor type 4 (CXCR4), proteolytic enzymes, and bone remodeling.

Prenatal Diagnosis of Different Polymorphisms of ß-globin Gene in Ahvaz.

BACKGROUND: Hemoglobinopathy and thalassemia are prevalent genetic disorders throughout the world. Beta thalassemia is one of these disorders with high prevalence in Iran, especially in Khuzestan province. In this study, the rate of different mutations in ß-globin gene for prenatal diagnosis in fetal samples was evaluated. MATERIALS AND METHODS: In this experimental pilot study, 316 fetal samples (chorionic villus or amniotic fluid) suspicious to hemoglobin disorders were enrolled. Afterwards, DNA was extracted and PCR and DNA sequencing were used for evaluation of different mutations in ß-globin gene. RESULTS: Amongst 316 samples evaluated for prenatal diagnosis, 180 cases (56.8%) were carrying at least one mutated gene of ß-thalassemia. In addition, results showed that CD 36-37 (- T) and IVS II-1 (G > A) polymorphisms are the most prevalent polymorphisms of ß-thalassemia in Ahvaz city with 13.9% and 10.1% rates, respectively. CONCLUSION: Using molecular tests for prenatal diagnosis is considered an efficient approach for reducing the birth of children with hemoglobinopathy and identification of prevalent mutations in each region.