ABSTRACT
B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is a heterogeneous leukemia subgroup. It has multiple sub-types that are likely to be classified by prognostic factors. Following a systematic literature review, this study analyzed the genes correlated with BCP-ALL prognosis ( IKZF1, PAX5, EBF1, CREBBP, CRLF2, JAK2, ERG, CXCR4, ZAP70, VLA4, NF1, NR3C1, RB1, TSLP, ZNRF1, and FOXO3A) , specifically their nucleotide variations and expression profiles in pediatric BCP-ALL samples. The study included 45 pediatric BCP-ALL patients with no cytogenetic anomaly and a control group of 10 children. The selected genes' hot-spot regions were sequenced using next-generation sequencing, while Polymorphism Phenotyping v2 and Supplemental Nutrition Assistance Program were used to identify pathogenic mutations. The expression analysis was performed using quantitative real-time polymerase chain reaction. The mutation analysis detected 328 variants (28 insertions, 47 indels, 74 nucleotide variants, 75 duplications, and 104 deletions). The most and least frequently mutated genes were IKZF1 and CREBBP , respectively. There were statistically significant differences between patients and controls for mutation distribution in eight genes ( ERG, CRLF2, CREBBP, TSLP, JAK2, ZAP70, FOXO3A, and NR3C1 ). The expression analysis revealed that JAK and ERG were significantly overexpressed in patients compared with controls (respectively, p = 0.004 and p = 0.003). This study combined genes and pathways previously analyzed in pediatric BCP-ALL into one dataset for a comprehensive analysis from the same samples to unravel candidate prognostic biomarkers. Novel mutations were identified in all of the studied genes.
ABSTRACT
OBJECTIVE: This study aimed to investigate the reasons behind the compliance, diagnostic success, and failure of ultrasound (US) examinations of two radiologists with reference to magnetic resonance imaging (MRI) in the abnormalities of subscapularis (SSC) tendon, including tendinosis. METHODS: One less experienced radiologist (operator-1) and one senior radiologist, experienced in the musculoskeletal US (operator-2), performed the shoulder US on 78 patients (mean age: 53.18 ± 10.89 [22-73] years), who had undergone MRI for routine reasons except malignancy, within 1-4 weeks of MRI. Tendinopathy, partial (PT), or full-thickness (FT) tears were recorded in the subscapularis. The thickness of the anterior and lateral soft tissues in the shoulder girdle was measured by MRI. The inter-operator agreement on the US results, the US-MRI compliance for each operator, and the relationship between the US-MRI compliance and tissue thickness were investigated. RESULTS: The inter-operator agreement on the US findings was moderate. The US-MRI compliance was fair for operator-1, but substantial for operator-2. The circumferential soft tissue thickness and US-MRI compliance were not correlated (p>0.05). The interobserver agreement in US was moderate (K: 0.415). The US-MRI compliance was fair for operator-1 (K: 0.344) and substantial for operator-2 (K: 0.616). The accuracy rates for the differentiation of normal tendon, tendinosis, PT, and FT were 59%, 75%, 72%, and 100%, respectively, for operator-1 and 87%, 83%, 85%, and 100%, respectively, for operator-2. However, the respective sensitivity of operator-1 was 46%, 19%, 44%, and 100%; and operator-2 was 91%, 67%, 82%, and 100%. The diagnostic performance of operator-1 was lower, except for FT. CONCLUSION: The thickness of the surrounding tissue does not affect the US results. The differentiation between tendinosis and PT tear is difficult (more prominent in less experienced user); however, because this would not change the treatment choice, shoulder US is recommended after basic training in subscapularis pathologies. LEVEL OF EVIDENCE: Level II, Diagnostic.
