MicroRNA is a small non-coding RNA (sncRNA) involved in gene silencing and regulating post-transcriptional gene expression. miRNAs play an essential role in the pathogenesis of numerous diseases, including diabetes, cardiovascular diseases, viral diseases and cancer. Diffuse large B-cell lymphoma (DLBCL) is an aggressive non-Hodgkin’s lymphoma (NHL), arising from different stages of B-cell differentiation whose pathogenesis involves miRNAs. Various viral and non-viral vectors are used as a delivery vehicle for introducing specific miRNA inside the cell. Adenoviruses are linear, double-stranded DNA viruses with 35 kb genome size and are extensively used in gene therapy. Meanwhile, Adeno-associated viruses accommodate up to 4.8 kb foreign genetic material and are favorable for transferring miRNA due to small size of miRNA. The genetic material is integrated into the DNA of the host cell by retroviruses so that only dividing cells are infected and stable expression of miRNA is achieved. Over the years, remarkable progress was made to understand DLBCL biology using advanced genomics and epigenomics technologies enabling oncologists to uncover multiple genetic mutations in DLBCL patients. These genetic mutations are involved in epigenetic modification, ability to escape immunosurveillance, impaired BCL6 and NF-κβ signaling pathways and blocking terminal differentiation. These pathways have since been identified and used as therapeutic targets for the treatment of DLBCL. Recently miRNAs were also identified to act either as oncogenes or tumor suppressors in DLBCL pathology by altering the expression levels of some of the known DLBCL related oncogenes. i.e., miR-155, miR-17-92 and miR-21 act as oncogenes by altering the expression levels of MYC, SHIP and FOXO1, respectively, conversely; miR-34a, mir-144 and miR-181a act as tumor suppressors by altering the expression levels of SIRT1, BCL6 and CARD11, respectively. Hundreds of miRNAs have already been identified as biomarkers in the prognosis and diagnosis of DLBCL because of their significant roles in DLBCL pathogenesis. In conclusion, miRNAs in addition to their role as biomarkers of prognosis and diagnosis could also serve as potential therapeutic targets for treating DLBCL.
A wide range of histological as well as clinical properties are exhibited by B-cell non-Hodgkin’s lymphomas. These properties could make the diagnostics process complicated. The diagnosis of lymphomas at an initial stage is essential because early remedial actions taken against destructive subtypes are commonly deliberated as successful and restorative. Therefore, better protective action is needed to improve the condition of those patients who are extensively affected by cancer when diagnosed for the first time. The development of new and efficient methods for early detection of cancer has become crucial nowadays. Biomarkers are urgently needed for diagnosing B-cell non-Hodgkin’s lymphoma and assessing the severity of the disease and its prognosis. New possibilities are now open for diagnosing cancer with the help of metabolomics. The study of all the metabolites synthesised in the human body is called “metabolomics.” A patient’s phenotype is directly linked with metabolomics, which can help in providing some clinically beneficial biomarkers and is applied in the diagnostics of B-cell non-Hodgkin’s lymphoma. In cancer research, it can analyse the cancerous metabolome to identify the metabolic biomarkers. This review provides an understanding of B-cell non-Hodgkin’s lymphoma metabolism and its applications in medical diagnostics. A description of the workflow based on metabolomics is also provided, along with the benefits and drawbacks of various techniques. The use of predictive metabolic biomarkers for the diagnosis and prognosis of B-cell non-Hodgkin’s lymphoma is also explored. Thus, we can say that abnormalities related to metabolic processes can occur in a vast range of B-cell non-Hodgkin’s lymphomas. The metabolic biomarkers could only be discovered and identified as innovative therapeutic objects if we explored and researched them. In the near future, the innovations involving metabolomics could prove fruitful for predicting outcomes and bringing out novel remedial approaches.
Background: Iron deficiency anemia (IDA) is a global health problem affecting the quality of life of more than 2 billion individuals. The current practice guidelines diagnose and monitor IDA via conventional hematological and iron biomarkers, which take several months before they are corrected under an iron-treatment plan. Reticulocyte hemoglobin equivalent (Ret-He) is used as a marker in most new hematology analyzers to assess iron incorporation into erythrocyte hemoglobin directly. This study aims to examine the efficacy of Ret-He as a marker for iron deficiency (ID) and IDA and investigate whether Ret-He is sensitive to iron therapy. Methods: Two blood samples were drawn from 182 participants for CBC and iron profile measurements. Follow-up samples were drawn from participants with a confirmed diagnosis of ID and/or IDA. Results: Ret-He levels were lower in the ID and IDA groups compared to the control (p < 0.0001), and lower in the IDA group compared to the ID group (p < 0.0001). Ret-He was correlated with ferritin at ID level (<30.0 mg/mL; r = 0.39) and severe IDA (<13.0 ng/mL; p-value < 0.01, r = 0.57). Cut-off values of <28.25 pg for ID and <21.55 pg for IDA showed a higher specificity and sensitivity (ID; AUC: 0.99, sensitivity: 92.73%, specificity: 97.87%) and (IDA; AUC: 0.94, sensitivity: 90.63%, specificity: 92.31%). Finally, Ret-He successfully reflected the iron therapy (p < 0.001) when compared to hemoglobin (Hb) (p = 0.1). Conclusions: Ret-He is a potential marker for detecting and diagnosing different stages of ID with high validity and is very sensitive in reflecting the iron incorporation in a short time.
B-cell lymphomas exhibit a vast variety of clinical and histological characteristics that might complicate the diagnosis. Timely diagnosis is crucial, as treatments for aggressive subtypes are considered successful and frequently curative, whereas indolent B-cell lymphomas are incurable and often need several therapies. The purpose of this review is to explore the current advancements achieved in B-cell lymphomas metabolism and how these indicators help to early detect metabolic changes in B-cell lymphomas and the use of predictive biological markers in refractory or relapsed disease. Since the year 1920, the Warburg effect has been known as an integral part of metabolic reprogramming. Compared to normal cells, cancerous cells require more glucose. These cancer cells undergo aerobic glycolysis instead of oxidative phosphorylation to metabolize glucose and form lactate as an end product. With the help of these metabolic alterations, a novel biomass is generated by the formation of various precursors. An aggressive metabolic phenotype is an aerobic glycolysis that has the advantage of producing high-rate ATP and preparing the biomass for the amino acid, as well as fatty acid, synthesis needed for a rapid proliferation of cells, while aerobic glycolysis is commonly thought to be the dominant metabolism in cancer cells. Later on, many metabolic biomarkers, such as increased levels of lactate dehydrogenase (LDH), plasma lactate, and deficiency of thiamine in B-cell lymphoma patients, were discovered. Various kinds of molecules can be used as biomarkers, such as genes, proteins, or hormones, because they all refer to body health. Here, we focus only on significant metabolic biomarkers in B-cell lymphomas. In conclusion, many metabolic biomarkers have been shown to have clinical validity, but many others have not been subjected to extensive testing to demonstrate their clinical usefulness in B-cell lymphoma. Furthermore, they play an essential role in the discovery of new therapeutic targets.
Background: In the era of the coronavirus disease-2019 (COVID-19) pandemic, the race toward shielding the public through vaccination is still going. Patients with sickle cell disease (SCD) require special consideration given their medical needs and the common side effects of immunization, affecting their decision. Therefore, we aimed to assess the perception and hesitancy toward COVID-19 vaccination in this population and explore the possible factors when it comes to vaccination decisions. Methods: The present cross-sectional phone interview study was conducted between May 10 and 20, 2021. The questionnaire was administered by the medical staff. The participants were all patients with SCD presented to King Abdulaziz University Hospital in Jeddah, Saudi Arabia. Results: Out of 346 patients, 147 patients agreed to participate. Only 52 (35.37%) patients received at least one dose of the nationally available vaccines, and there were no reported serious side effects. Among the unvaccinated participants, 45 patients (47.8%) were undecided. The most reported reasons for hesitancy were the fear of developing complications as their acquaintance had and the fear of developing brain blood clots post vaccination. Conclusions: The number of vaccinated patients with SCD was unfortunately low in our study, secondary to hesitancy. This represents a significant barrier and needs to be tackled appropriately at any proper interaction with a patient with SCD. The absence of major side effects and vaso-occlusive crises is assuring.
Introduction: Studies assessing immune responses following Pfizer-BioNTech BNT162b2 mRNA COVID-19 (Pfizer) and ChAdOx1 nCoV-19 AZD1222 (AstraZeneca) vaccines in patients with hemoglobinopathy are non-existent in the literature despite being thought at high risk of infection. Methods: Prospectively, we collected serum from patients with hemoglobinopathies at least 14 days post vaccine and measured neutralizing antibodies (nAb) in addition to binding antibodies using in-house assays. Results: All 66 participants mounted a significant binding antibody response (100%), but nAbs were detected in (56/66) post-vaccine with a rate of 84.5%. Age, gender, vaccine type, spleen status, hydroxyurea use, and hyperferritinemia did not affect the rate significantly. While 23/32 (71.8%) patients receiving only one dose of the vaccine were able to mount a positive response, 33/34 (97.05%) of those who had two doses of any vaccine type had a significant nAbs response. Patients who had anti-nucleocapsid (N), signifying asymptomatic infection in the past, were able to produce nAbs (31/31). No nAbs were detected in 10/35 (28.5%) patients with no anti-N antibodies. Conclusion: Our results provide supportive data when advising patients with hemoglobinopathy to receive COVID-19 vaccines and ensure booster doses are available for better immunity. Whenever available, measurement of nAb is recommended.
About Me
Associate Professor of Hematology, Hematology Consultant
Associate Professor of Hematology, Hematology Consultant