Bcl11a

This study reports the first case of a patient with chromosomal 2p16.1p15 microduplication syndrome complicated by pulmonary arterial hypertension (PAH). A female infant was admitted to the hospital suffering from dyskinesia and developmental delay, and conventional echocardiography revealed an atrial septal defect (ASD), which was not taken seriously or treated at that time. Two years later, preoperative right heart catheterization for ASD closure revealed a mean pulmonary artery pressure (mPAP) of 45 mmHg...

BACKGROUND AND OBJECTIVE: Beta-thalassemia major (β-Thal) and compound heterozygote of Sickle β-thalassemia (S-β Thal) are hereditary autosomal recessive disorders resulting from mutations or deletion in β-globin gene cluster. Patients with increased HbF levels having polymorphism at BCL11A site loci have shown clinical significance. The present study aimed to assess the frequency of BCL11A gene polymorphism in a study population of β-Thal, S-β Thal & Controls using Sanger sequencing leading to plot the HbF response of polymorphism with reference to wild type...

In humans, specific aberrations in β-globin results in sickle cell disease and β -thalassemia, symptoms of which can be ameliorated by increased expression of fetal globin (HbF). Two recent CRISPR-Cas9 screens, centered on ∼1500 annotated sequence-specific DNA binding proteins and performed in a human erythroid cell line that expresses adult hemoglobin, uncovered four groups of candidate regulators of HbF gene expression. They are (1) members of the nucleosome remodeling and deacetylase (NuRD) complex proteins that are already known for HbF control; (2) seven C2H2 zinc finger (ZF) proteins, including some (ZBTB7A and BCL11A) already known for directly silencing the fetal γ-globin genes in adult human erythroid cells; (3) a few other transcription factors of different structural classes that might indirectly influence HbF gene expression; and (4) DNA methyltransferase 1 (DNMT1) that maintains the DNA methylation marks that attract the MBD2-associated NuRD complex to DNA as well as associated histone H3 lysine 9 methylation...

Activating transcription factor 4 (ATF4) is a fundamental basic region/leucine zipper transcription factor, responds to various stress signals, and plays crucial roles in normal metabolic and stress response processes. Although its functions in human health and disease are not completely understood, compelling evidence underscores ATF4 is indispensable for multiple stages and lineages of erythroid development, including the regulation of fetal liver hematopoietic stem cells, induction of terminal erythroid differentiation, and maintenance of erythroid homeostasis...

The anticancer drug mithramycin (MTH), has been proposed for drug repurposing after the finding that it is a potent inducer of fetal hemoglobin (HbF) production in erythroid precursor cells (ErPCs) from β-thalassemia patients. In this respect, previously published studies indicate that MTH is very active in inducing increased expression of γ-globin genes in erythroid cells. This is clinically relevant, as it is firmly established that HbF induction is a valuable approach for the therapy of β-thalassemia and for ameliorating the clinical parameters of sickle-cell disease (SCD)...

Lymphocystis disease is frequently prevalent and transmissible in various teleost species worldwide due to lymphocystis disease virus (LCDV) infection, causing unsightly growths of benign lymphocystis nodules in fish and resulting in huge economic losses to aquaculture industry. However, the molecular mechanism of lymphocystis formation is unclear. In this study, LCDV was firstly detected in naturally infected flounder ( Paralichthys olivaceus ) by PCR, histopathological, and immunological techniques. To further understand lymphocystis formation, transcriptome sequencing of skin nodule tissue was performed by using healthy flounder skin as a control...

IMPORTANCE: Sickle cell disease (SCD) is a monogenic disorder, yet clinical outcomes are influenced by additional genetic factors. Despite decades of research, the genetics of SCD remain poorly understood. OBJECTIVE: To assess all reported genetic modifiers of SCD, evaluate the design of associated studies, and provide guidelines for future analyses according to modern genetic study recommendations. DATA SOURCES: PubMed, Web of Science, and Scopus were searched through May 16, 2023, identifying 5290 publications...

BACKGROUND: The B cell CLL/lymphoma 11A (BCL11A) is a key regulator of hemoglobin switching in β-thalassemia (β-thal). Previous study has suggested that dysregulated microRNAs are involved in the regulation of BCL11A expression. The aim of this study was to investigate the clinical value of hsa-miR-190b-5p in β-thal, and to confirm the regulatory effect of hsa-miR-190b-5p on BCL11A expression. METHODS: The peripheral blood of 25 pediatric β-thal patients and 25 healthy controls were selected, and qRT-PCR was used to analyze the levels of hsa-miR-190b-5p and BCL11A mRNA...

OBJECTIVE: A multitude of observational studies have underscored a substantial comorbidity between COVID-19 and epilepsy. This study was aimed at establishing a conclusive causal link between these two conditions. METHODS: We employed Mendelian randomization (MR) to evaluate the causal link between COVID-19 and epilepsy, as well as its focal and generalized subtypes. The GWAS for epilepsy and its subtypes database were abstracted from both FinnGen consortium and ILAE...

Transcription factors (TFs) regulate gene expression via direct DNA binding together with cofactors and in chromatin remodeling complexes. Their function is thus regulated in a spatiotemporal and cell-type-specific manner. To analyze the functions of TFs in a cell-type-specific context, genome-wide DNA binding, as well as the identification of interacting proteins, is required. We used i -GONAD (improved genome editing via oviductal nucleic acids delivery) in mice to genetically modify TFs by adding fluorescent reporter and affinity tags that can be exploited for the imaging and enrichment of target cells as well as chromatin immunoprecipitation and pull-down assays...

Hemoglobin switching is a complex biological process not yet fully elucidated. The mechanism regulating the suppression of fetal hemoglobin (HbF) expression is of particular interest because of the positive impact of HbF on the course of diseases such as β-thalassemia and sickle cell disease, hereditary hemoglobin disorders that affect the health of countless individuals worldwide. Several transcription factors have been implicated in the control of HbF, of which BCL11A has emerged as a major player in HbF silencing...

We previously reported initial clinical results of post-transcriptional gene silencing of BCL11A expression (NCT03282656) reversing the fetal to adult hemoglobin switch. A goal of this approach is to increase fetal hemoglobin (HbF) expression while coordinately reducing sickle hemoglobin (HbS) expression. The resulting combinatorial effect should prove effective in inhibiting HbS polymerization at lower physiologic oxygen values thereby mitigating disease complications. Here we report results of exploratory single-cell analysis of patients in which BCL11A is targeted molecularly and compare results with cells of patients treated with hydroxyurea (HU), the current standard of care...

BACKGROUND: Increased hemoglobin F (HbF) expression in individuals with β-thalassemia contributes to the alleviation of pathological phenomena and the reduction of mortality. We have investigated the correlation between six single nucleotide polymorphisms (SNPs) in BCL11A, XmnI-HBG2, HBS1L-MYB, and ANTXR1 and the levels of HbF in β-thalassemia carriers. METHODS: Samples were collected from 330 cases of β-thalassemia carriers. The genotypes of the rs4671393, rs-7482144, rs28384513, rs4895441, rs9399137, and rs4527238 were determined using Sanger sequencing...

Based on a few studies, heart failure patients with breast cancer were assessed to find potential biomarkers for doxorubicin-induced cardiotoxicity. However, key immune-related transcriptional markers linked to doxorubicin-induced cardiotoxicity in breast cancer patients have not been thoroughly investigated. We used GSE40447, GSE76314, and TCGA BRCA cohorts to perform this study. Then, we performed various bioinformatics approaches to identify the key immune-related transcriptional markers and their association with doxorubicin-induced cardiotoxicity in patients with breast cancer...

OBJECTIVE: The aim of this study was to determine frequency of secondary modifiers in non-transfusion dependent thalassemia. METHODS: This descriptive cross sectional study was done at Fauji Foundation Hospital Islamabad. Seventy diagnosed patients of thalassemia intermedia were included. Deoxyribonucleic acid (DNA) was extracted using Chelex method. The Xmn-1 and BCL11A polymorphisms were analyzed by Amplification Refractory Mutation System (ARMS) and Restriction Fragment Length Polymorphism (RFLP) PCR...

The fetal liver (FL) is the key erythropoietic organ during fetal development, but knowledge on human FL erythropoiesis is very limited. In this study, we sorted primary erythroblasts from FL cells and performed RNA sequencing analyses. We found that temporal gene expression patterns reflected changes in function during primary human FL terminal erythropoiesis. Notably, the expression of genes enriched in proteolysis and autophagy was upregulated in orthochromatic erythroblasts (OrthoE), suggesting the involvement of these pathways in enucleation...

Pharmacological induction of fetal hemoglobin has proven to be a promising therapeutic intervention in β-hemoglobinopathies by reducing the globin chain imbalance and inhibiting sickle cell polymerization. Fagonia indica has shown therapeutic relevance to β-thalassemia. Therefore, we study the ethnopharmacological potential of Fagonia indica and its biomarker compounds for their HbF induction ability for the treatment of β-thalassemia. Here, we identify, compound 8 (triterpenoid glycosides) of F...

BACKGROUND: The function of long non-coding RNA (lncRNA) MALAT1 in regulating triple-negative breast cancer (TNBC) stemness and tumorigenesis was investigated. METHODS: Sphere formation and colony formation assays coupled with flow cytometry were employed to evaluate the percentage of CD44high /CD44low cells, and ALDH+ cells were performed to evaluate the stemness. Bisulfite sequencing PCR (BSP) was employed to detect the methylation level of MALAT1. Tumor xenograft experiment was performed to evaluate tumorigenesis in vivo ...

Genome editing (GE) is one of the most efficient and useful molecular approaches to correct the effects of gene mutations in hereditary monogenetic diseases, including β-thalassemia. CRISPR-Cas9 gene editing has been proposed for effective correction of the β-thalassemia mutation, obtaining high-level " de novo " production of adult hemoglobin (HbA). In addition to the correction of the primary gene mutations causing β-thalassemia, several reports demonstrate that gene editing can be employed to increase fetal hemoglobin (HbF), obtaining important clinical benefits in treated β-thalassemia patients...

No abstract text is available yet for this article.