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This nonrandomized, multicenter cohort, open-label clinical trial evaluated the efficacy and safety of combined chemotherapy with arsenic trioxide (ATO) in children with stage 4/M neuroblastoma (NB). We enrolled patients who were newly diagnosed with NB and assessed as stage 4/M and received either traditional chemotherapy or ATO combined with chemotherapy according to their own wishes. Twenty-two patients were enrolled in the trial group (ATO combined with chemotherapy), and 13 patients were enrolled in the control group (traditional chemotherapy). Objective response rate (ORR) at 4 weeks after completing induction chemotherapy was defined as the main outcome, and adverse events were monitored and graded in the meantime. Data cutoff date was December 31, 2019. Finally, we found that patients who received ATO combined with chemotherapy had a significantly higher response rate than those who were treated with traditional chemotherapy (ORR: 86.36% vs. 46.16%, p =0.020). Reversible cardiotoxicity was just observed in three patients who were treated with ATO, and no other differential adverse events were observed between the two groups. ATO combined with chemotherapy can significantly improve end-induction response in high-risk NB, and our novel regimen is well tolerated in pediatric patients. These results highlight the superiority of chemotherapy with ATO, which creates new opportunity for prolonging survival. In addition, this treatment protocol minimizes therapeutic costs compared with anti-GD2 therapy, MIBG, and proton therapy and can decrease the burden to families and society. However, we also need to evaluate more cases to consolidate our conclusion. [ABSTRACT FROM AUTHOR]

Increased levels of fetal hemoglobin (HbF: α2γ2) can ameliorate the clinical severity of the β‐hemoglobinopathies. Microarray analysis represents a powerful approach to identify novel genetic factors regulating the γ‐globin gene. Gene expression profiling was previously performed on 14 individuals with high or normal HbF levels to identify the genetic factors that control γ‐globin gene expression. To obtain more accurate and reliable results, our results were combined with public microarray dataset GSE22109 deposited in the Gene Expression Omnibus database. Annotation of case versus control samples was taken directly from the microarray documentation. The differentially expressed genes (DEGs) were obtained and were deeply analyzed by bioinformatics methods. Combined with our own chip expression data, potential genes HBE1, TFRC, and CSF2 were selected out for subsequent qRT‐PCR validation. A total of 184 DEGs were identified from GSE22109 and the protein–protein interaction network was constructed. Gene set enrichment analysis showed that the hematopoietic cell lineage pathway overlaps in the two datasets. HBE1, CSF2, and TFRC were confirmed by qRT‐PCR. Our results suggest novel candidate genes and pathways associated with the γ‐globin gene expression. [ABSTRACT FROM AUTHOR]

Abstract: This study's purposes were to diagnose intractable hemolytic anemia and to provide guiding treatment for the affected family members. We performed NGS in a panel of 600 genes for blood diseases on a patient with obscure hemolytic anemia and her parents. We confirmed the diagnosis of pyruvate kinase deficiency, identified a novel homozygous mutation of the PKLR gene ( NM_000298: exon 6: c.T941C: p.I314T), and ruled out other blood diseases in the Chinese family. Furthermore, amniotic fluid was taken from the mother during the second trimester, and DNA was extracted to analyze the type of PKLR gene mutation. The proband received cord blood and bone marrow from the second child of the mother for hematopoietic stem cell transplantation and achieved normal hematopoiesis. The genetic characterization analysis and genotype‐phenotype correlation study of PKLR gene suggested that NGS was an effective method to confirm the molecular diagnosis of intractable hemolytic anemia. The identification of the mutation aided in prenatal diagnosis in the second pregnancy and the effective clinical management of the affected family. [ABSTRACT FROM AUTHOR]

Foetal haemoglobin (HbF) plays a dominant role in ameliorating the morbidity and mortality of β-thalassaemia. A better understanding of the loci and genes involved in HbF expression would be beneficial for the treatment of β-thalassaemia major. However, the genes associated with HbF expression remain largely unknown. In this study, we first explored large-scale data sets and examined the human genome for evidence of positive natural selection to screen out single nucleotide polymorphisms (SNPs). A genetic analysis of HbF levels was conducted in a Chinese cohort of patients with β-thalassaemia to confirm the bioinformatics results. A total of 1141 subjects with β-thalassaemia were recruited. The results showed that the SNP rs11759328 in the ARHGAP18 gene was significantly associated with HbF levels (Ρ = 5.1 × 10−4). ARHGAP18 belongs to the RhoGAP family and controls angiogenesis, cellular morphology and motility. Second, after determining that ARHGAP18 was highly expressed in the human K562 cell line, we used lentiviral-mediated small interfering RNA to knock down ARHGAP18 expression and subsequently assessed cell proliferation and apoptosis using cell proliferation assays and flow cytometry, respectively. ARHGAP18 downregulation in K562 cells significantly increased HBG1/2 expression and apoptosis, but proliferation was not significantly affected in vitro. Our data suggest that ARHGAP18, which was located by the SNP rs11759328 via positive selection, plays a potential role in regulating HbF expression in β-thalassaemia and may be a promising therapeutic target. Knockout studies of ARHGAP18 warrant further investigation into its aetiology in HbF. [ABSTRACT FROM AUTHOR]

β-Thalassemia (β-thal) is the most common inherited hemolytic anemia worldwide. Elevated Hb A2is a mark of β-thal carriers. The aim of this study was to identify the pathogenic variants associated with the Hb A2levels. One thousand and thirty β-thal carriers were recruited for this study. Using positive natural expression quantitative trait loci (eQTL) analysis, a significant variant was selected. Genotyping for the rs231841 polymorphism was performed by the Sequenom MassARRAY IPLEX platform. All genetic association analyses were performed with the PLINK program. The linear regression analysis showed that rs231841 in the intron region of the potassium voltage-gated channel subfamily Q member 1 (KCNQ1) gene on chromosome 11p15 was significantly associated with Hb A2levels. The presence of the C allele was associated with elevated Hb A2levels. Our results suggest that rs231841 on theKCNQ1gene with positive natural selection is related to Hb A2levels in Chinese β-thal carriers, andKCNQ1is probably associated with the expression of the β-like globin gene cluster. [ABSTRACT FROM AUTHOR]

Hb E [β26(B8)Glu→Lys]/β-thalassemia (β-thal) is a worldwide inherited disorder. We determined the phenotype of 65 unrelated Hb E/β-thal subjects and 70 healthy individuals in the Guangxi Province of the Republic of China (ROC). Single nucleotide polymorphism (SNP) rs35959442 in HBS1L analysis was performed using the polymerase chain reaction (PCR)/restriction enzyme method. The data suggested that the frequency of the rs35959442 polymorphism was relatively high in patients with Hb E/β-thal in Guangxi Province, ROC, when associated with Hb F augmentation. [ABSTRACT FROM AUTHOR]