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

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.

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

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.

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

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.

Deep vein thrombosis: a less noticed complication in hematologic malignancies and immunologic disorders.

Deep vein thrombosis (DVT) is a common complication in hematologic malignancies and immunologic disorders that coagulation and inflammatory factors play a crucial role in its occurrence. The content used in this article has been obtained by PubMed database and Google Scholar search engine of English-language articles (1980-2019) using the "Deep vein thrombosis," "Hematologic malignancies," "Immunologic disorders" and "Treatment." Increased levels of coagulation factors, the presence of genetic disorders, or the use of thrombotic drugs that stimulate coagulation processes are risk factors for the development of DVT in patients with hematologic malignancies. Inflammatory and auto-anti-inflammatory factors, along with coagulant factors, play an essential role in the formation of venous thrombosis in patients with immunological disorders by increasing the recruitment of inflammatory cells and adhesion molecules. Therefore, anti-coagulants in hematologic malignancies and immunosuppressants in immune disorders can reduce the risk of developing DVT by reducing thrombotic and inflammatory activity. Considering the increased risk of DVT due to impaired coagulation and inflammation processes, analysis of coagulation and inflammatory factors have prognostic values in patients with immunologic deficiencies and hematologic malignancies. Evaluation of these factors as diagnostic and prognostic biomarkers in the prediction of thrombotic events could be beneficial in implementing effective treatment strategies for DVT.

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

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.

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

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.

The Expression of Microvesicles in Leukemia: Prognostic Approaches.

Microvesicles (MVs) are the smallest subclass of the extracellular vesicles (EVs) spontaneously secreted by the external budding from the cell membranes in physiologic and pathologic conditions. The MVs derived from leukemic cells (LCs) can be detected by the expression of specific cluster of differentiation (CD) markers indicating their cellular origin while they can transfer different agents such as microRNAs, cytokines, and chemokines. The secretion of these agents from MVs can affect the vital processes of LCs such as cell cycle, proliferation, differentiation, and apoptosis. According to the effects of MVs components on the vital processes of LCs, it has been postulated that a change in the expression of MVs might be involved in the progression and prognosis of leukemia. However, further studies are needed to confirm the association between the presence of MVs and their components with the prognosis of leukemia. It seems that the identification of the prognostic values and the application of them for the detection of MVs in leukemia can provide new therapeutic targets for monitoring the status of patients with leukemia.

Expression and Activity of Matrix Metalloproteinases in Leukemia.

Matrix metalloproteinases (MMPs) are responsible for the degradation of extracellular matrix components and hence play a crucial role in physiological and pathologic processes. The imbalance between the expression of MMPs and their inhibitors can be effective in leukemic cell processes such as migration, angiogenesis, survival, and apoptosis, playing a key role in the progression and prognosis of leukemia. In this review, we discuss the potential involvement of MMPs and their inhibitors in the pathogenesis and progression of leukemia by examining their role in the prognosis of leukemia. Inducing leukemic cell growth, migration, invasiveness, and angiogenesis are the main roles of MMPs in leukemia progression mediated by their degradative activity. Given the important role of MMPs in leukemia progression, further clinical trials are needed to confirm the link between MMPs' expressions and leukemia prognosis. It is hoped to use MMPs as therapeutic targets to improve patients' health by recognizing the prognostic value of MMPs in leukemia and their effect on the progression of these malignancies and their response to treatment.