Iranian Journal of Blood and Cancer
Volume:16 Issue: 1, Mar 2024

This document is a comprehensive review that focuses on the role of melanoma-associated antigen genes (MAGE) family proteins in cancer, with a specific emphasis on their involvement in multiple myeloma (MM). The expression patterns of MAGE proteins in different tissues and their association with critical cellular processes such as cell cycle progression, apoptosis, and gene expression regulation were discussed. The document also highlighted the potential utility of MAGE proteins in cancer immunotherapy, including their use in prognosis and the development of MAGE-based cancer vaccines. In cancer vaccine therapy antigen selection is a crucial step, so by focusing on the vast potency of MAGE, we tried to mention it as a potent antigen for therapy of MM by reviewing the current studies. However, we acknowledged the need for further research and extensive clinical trials to evaluate the effectiveness, safety, and potency of MAGE antigens.

Ikaros zinc finger (IKZF) transcription factors, part of the Krüppel family, have a significant role in the physiological development of immune cells. Ikaros, which is encoded by IKZF1, is a well-researched IKZF transcription factor that specifically impacts the growth and differentiation of lymphocytes. It interacts with various nuclear factors, functioning as either a transcriptional inhibitor or activator; thus, regulates several lymphopoiesis-associated factors like pre-TCR and pre-BCR. Over the years, research has revealed that alterations in IKZF1 as well as Ikaros can cause out-of-control differentiation and proliferation of immune cells, particularly lymphocytes, potentially triggering tumorigenesis in hematologic malignancies such as ALL, AML, CLL, and CML. Recent studies have explored the therapeutic potential of targeting Ikaros or restoring its activities to limit the pathologic differentiation and proliferation of tumor cells. Most of these therapeutic agents are immunomodulatory drugs (IMiDs) that can selectively ubiquitinate and proteasome degrade Ikaros. This study offers a comprehensive overview of Ikaros’s physiological roles and highlights the oncogenic characteristics of IKZF1 and Ikaros alterations.

Acute Lymphoblastic Leukemia (ALL) is the most prevalent cancer among children, necessitating an investigation of its associated complications and comorbidities. Of particular concern is the frequent occurrence of obesity in patients undergoing treatment for childhood leukemia. Obesity is recognized as a risk factor for various cardiovascular conditions, venous thromboembolism (VTE), hypertension, hyperglycemia, diabetes mellitus and non-insulin-dependent diabetes mellitus (NIDDM). Consequently, a comprehensive examination of this issue from multiple perspectives is essential. The disturbance in gut microbiota diversity, resulting from the administration of Chemotherapy drugs and Antibiotics to these patients, may contribute to the development of obesity. Given the heightened risk of obesity in children with ALL, it is imperative to explore the relationship between obesity and factors such as antibiotic usage in this population. This review aims to synthesize and analyze the most recent published evidence concerning the association of obesity and antibiotics in pediatric ALL. Through this comprehensive analysis, we seek to shed light on the intricate interplay between antibiotics, obesity, and childhood ALL, with the ultimate goal of guiding future research and clinical interventions.

Introduction: 

Thalassemia, particularly α and β types, are characterized by mutations causing varied clinical manifestations such as anemia, skeletal deformities, and iron accumulation. Patients with transfusion-dependent thalassemia (TDTs) often face growth and puberty complications, which are influenced by the disease’s type and severity. These disruptions not only result from chronic anemia, iron chelation therapy, and endocrinopathies but also significantly impact the patient’s quality of life.

A comprehensive guideline was formulated through a systematic literature review and stakeholder engagements. The protocol emphasizes diagnosing and managing growth and puberty disorders in TDT patients, integrating consistent monitoring, documentation, and patient-specific assessments.

The guideline proposes a detailed monitoring schedule from birth to adulthood, focusing on growth velocity norms and referral criteria to pediatric endocrinologists. It outlines protocols for hormone treatments in cases of delayed or arrested puberty, with distinctions for boys and girls. The treatment approach is multidisciplinary, combining growth monitoring, hormone therapy, and potential surgical interventions. The complexities demand continuous management, with treatment plans tailored to individual patient needs.

The research provides a pivotal national protocol for addressing growth and puberty anomalies in TDT patients, aiming to enhance their well-being and standardize care. The emphasis on proactive, individualized strategies will bolster healthcare outcomes and reduce associated costs.

The health-related quality of life and management of patients with thalassemia has significantly improved in recent years due to standard treatments and safe blood transfusions with effective chelation therapy to reduce iron overload. Transfusion-dependent thalassemia is associated with numerous skeletal abnormalities, including osteoporosis, which is a significant cause of morbidity in these patients. Osteoporosis is characterized by low bone mass and an increased risk of fractures, particularly in the lumbar spine and in patients with extramedullary hematopoiesis. It remains a significant problem in adult transfusion-dependent thalassemia, particularly in patients under chelation therapy. A fracture history is significantly associated with lower Dual-Energy X-ray Absorptiometry (DEXA) T/Z scores, which decrease with age. Improved management and modern treatments for transfusion-dependent thalassemia patients with osteoporosis should be prioritized to prevent bone fractures and improve quality of life in older age.

The role of Plasma-Derived Medicinal Products (PDMPs) in managing life-threatening diseases is remarkable. Human plasma as a raw material for PDMPs is obtained from volunteers through apheresis or whole blood collection. The global PDMPs market in 2021 shows an average annual growth rate of 7.4% since 1996 which is higher than the average annual pharmaceutical market growth rate. In line with WHO policies, Iran has improved its national voluntary non-remunerated donors (VNRD) program to supply the local PDMPs market. This study shows the 10-year Iran PDMPs market evolution to assess its self-sufficiency.

We conducted a cross-sectional study from 2012 to 2021 to assess the self-sufficiency rate of Iran’s plasma industry for PDMPs including Albumin, Immune globulins, and Antihemophilic Factors. In addition, we show the gap between market supply and demand to lighten the self-sufficiency future.

The annual growth rate of total collected plasma was 18.9% over 10 years in Iran from 2012 to 2021. Although the consumption rate of intravenous Immune globulins has increased from 777 kg to 2,108 Kg, due to a significant increase in local plasma production, its self-sufficiency rate increased from 53% to 93%.  Similarly, the demand rate for Albumin grew from 21% in 2012 to 90% in 2021.

Although local plasma production in Iran significantly provided plasma self-sufficiency as a raw material, local market demand for PDMPs is mainly supplied through contract fractionation with European fractionators.  Access to complete self-sufficiency in Iran needs increasing plasma production, as well as developing major local plasma fractionators.

 Epigenetics is crucial in differentiating mesenchymal stem cells (MSCs) into adipocytes. Specifically, DNA methylation, an epigenetic modification, regulates the expression of genes involved in this process. The peroxisome proliferator-activated receptor gamma (PPARγ) gene is a critical player in adipocyte differentiation, with epigenetic changes affecting its expression.

We isolated mesenchymal stem cells (MSCs) from the human bone marrow. The isolated MSCs were expanded and cultured in a differentiation medium for two weeks. DNA extraction was performed on undifferentiated and differentiated adipocytes after the culturing process. The methylation status of the promoter region of the PPARγ gene was assessed using methylation-specific primers (M for methylated and U for unmethylated) in a methylation-specific PCR (MSP) assay. This analysis involved the treatment of DNA samples with sodium bisulfite to convert unmethylated cytosine to uracil, thereby enabling the differentiation between methylated and unmethylated regions of the gene.

 The successful differentiation of MSCs into adipocytes was confirmed by the accumulation of lipid droplets within the differentiated cells, as visualized by the oil Red O dye staining. This observation provides strong evidence of the commitment of MSCs towards the adipogenic lineage and their ability to undergo adipocyte differentiation. Surprisingly, the MSP analysis revealed no significant changes in the methylation pattern of this gene following differentiation. The PPARγ gene promoter region exhibited an unmethylated status in both undifferentiated and differentiated states.

Our study revealed that additional genetic or epigenetic mechanisms control the expression of PPARγ during the adipogenic differentiation of mesenchymal stem cells. These findings highlight the regulatory role of PPARγ in the differentiation pathway from mesenchymal stem cells to adipocytes.

Many studies have suggested Mesenchymal stem cells, as a promising way to develop new treatment strategies for different types of disease. However, due to their possible tumorigenic effects, their clinical use has been limited. Since a great deal of MSCs’ therapeutic benefits depend on MSC-derived extracellular vesicles, these particles have been receiving much attention in the past couple of years. With this in mind, we aimed to study the Effects of both peripheral blood mononuclear cells and human umbilical cord MSC-derived extracellular vesicles on cell growth, proliferation, and apoptosis of the Nalm6 cell line.

Isolated HUCMSCs were cultured, and PBMCs were acquired using the Ficoll-Hypaque technique. Their EVs were then extracted. The Nalm6 cells were divided into five groups: a control group and four treatment groups, which were treated with MSC- and MNC-derived EVs at different concentrations. Cell viability and metabolic assays were evaluated using trypan blue staining and the MTT assay, respectively. Thereafter, a flow cytometric assay was performed to detect cell cycle progression and apoptosis.

Our research revealed that the level of metabolic activity between Nalm6-treated EVs and the control group was not significantly different after 3 days. Also, no significant changes were reported in the growth and apoptosis effects of EVs on Nalm6 cells compared to the control group. Furthermore, different concentrations of EVs didn’t cause any inhibition on tumor growth.

Obtained EVs neither showed any anti-tumor effect nor caused any progression or aggressiveness in the Nalm6 cell line.

Owing to the synergistic effects of omega-3 fatty acids with chemotherapeutic agents in boosting response rates in gastric cancer (GC) patients, they became a promising addition to cancer therapy. Due to microRNAs (miRNAs) involvement in various cellular functions, their alterations in response to therapeutic interventions can offer insight into the efficacy of treatments. Our objective was to investigate docosahexaenoic acid (DHA) effects in conjunction with docetaxel on miR-30a-5p and miR-126-5p expressions in the MKN-45 cell line.

The CancerMIRNome database was used to investigate miR-30a-5p and miR-126-5p expression changes, as well as their relation to diagnosis and survival in GC patients. Then, MKN-45 cells were treated with docetaxel, DHA, and their combination. Later, RT-qPCR was performed to measure miR-30a-5p and miR-126-5p expression levels.

It was discovered that miR-30a-5p and miR-126-5p expression were both decreased in GC patients and associated with GC diagnosis and survival, respectively. Following treatment with docetaxel and docetaxel-DHA, miR-30a-5p and miR-126-5p expression levels increased. Of course, the increase in miRNAs' expression observed in the combination form was not as strong as docetaxel alone. DHA alone decreased miR-30a-5p and miR-126-5p expressions.

miR-30a-5p and miR-126-5p have important roles in GC tumorigenesis, and response to docetaxel and DHA. Attenuating effects of DHA on miR-30a-5p and miR-126-5p expression levels appear to counteract the beneficial effects of docetaxel on these miRNAs. Therefore, even though there is evidence of the anti-cancer effects of DHA in GC, not all DHA effects are anti-cancer.

Despite the low incidence rate of cervical cancer, the mortality-to-incidence ratio from this cancer is currently high in Iran, because it is diagnosed in advanced stages. This study aims to determine the prevalence and predictors of cervical cancer screening among women.

 This cross-sectional study was conducted in Kerman, Iran, 2022. The study population included women aged 21-65 years old referring to primary health care centers and maternity ward of Afzalipour Hospital. The sample size was calculated as 400 individuals. The participants were selected using the convenience sampling method. The data were collected based on the health belief model questionnaire and the validity and reliability of the Persian version were assessed by the researchers. The data were analyzed using SPSS 22.0.

A total of 372 respondents, 191 (51.3%) had a Pap smear test and 11 (3%) received the HPV vaccine. The participants reported lack of sufficient information as the main reason for not receiving the vaccine (79.2%). Our finding indicated that older age (P<0.001), increasing perceived seriousness of cervical cancer (P=0.006) and decreasing perceived barriers to undergoing a Pap smear test (P<0.001) increase the odds of having a Pap smear test.

 The results of the present study underscore the need for increasing knowledge with an emphasis on the perceived seriousness of cervical cancer among women. Additionally, the health system should cover the costs of Pap smear test, HPV test, and HPV vaccination to reduce the incidence and mortality of cervical cancer in Iran.