Genome-wide analysis of aberrantly expressed lncRNAs and miRNAs with associated co-expression and ceRNA networks in -thalassemia and hereditary persistence of fetal hemoglobin Genome-wide analysis of aberrantly expressed lncRNAs and miRNAs with associated co-expression and ceRNA networks in β-thalassemia and hereditary persistence of fetal hemoglobin

CD20 is a B-cell differentiation antigen that is expressed variably in precursor B-cell acute lymphoblastic leukemia (BCP-ALL). The prognostic significance of CD20 expression in childhood BCP-ALL remains controversial. Some studies have demonstrated that CD20 overexpression correlates with worse survival in pediatric patients with BCP-ALL, but some other studies suggest a better outcome. To explore the prognostic role of high CD20 expression in pediatric BCP-ALL, we performed a meta-analysis of the previous studies that provided survival information according to CD20 expression status. Pooled hazard ratios (HRs) indicated that high CD20 expression had no inferior impact on the prognosis of pediatric BCP-ALL. The summary HR for overall survival was 0.70 and combined HR for event-free survival was 1.01. These findings suggest that high CD20 expression does not influence the outcome for pediatric BCP-ALL. CD20 may lack prognostic value in children with BCP-ALL.

Magnetic resonance imaging (MRI) T2* is the gold standard for detecting iron deposition in cardiac tissue, but the technique has limitations and cannot be fully performed in paediatric thalassemia patients. The aim of this study was to analyse clinical data to identify other predictors of cardiac iron deposition. A retrospective analysis was performed on 370 children with β-TM. According to the cardiac MRI results, patients were allocated to a cardiac deposition group and noncardiac deposition group. Multivariate analysis revealed that genotype and corrected QT interval were associated with cardiac iron deposition, indicating that the-β⁰/β⁰ genotype conferred greater susceptibility to cardiac iron deposition. Receiver operating characteristic curve (ROC) analysis was performed, and the area under the curve (AUC) of genotype was 0.651. The AUC for the corrected QT interval was 0.711, at a cut-off value of 418.5 ms. ROC analysis of the combined genotype and corrected QT interval showed an AUC of 0.762 with 81.3% sensitivity and 64.7% specificity. Compared to patients with the β⁺/β⁺ and β⁰β⁺ genotypes, β⁰β⁰ children with β-TM were more likely to have cardiac iron deposition.  Conclusion: The genotype and QTc interval can be used to predict cardiac iron deposition in children with β-TM who are unable to undergo MRI T2 testing.

Introduction: Our study investigated the potential of peripheral blood T cell CD25, CD28, and CTLA-4 gene transcription levels as predictive biomarkers for acute graft-versus-host disease (aGVHD) following allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods: Real-time reverse transcription fluorescent quantitative PCR (RT-qPCR) analysis was conducted on day +7, +14, and +21 post-transplantation in patients undergoing allo-HSCT.Results: Elevated levels of CD25 and CTLA-4 mRNA were found to be associated with the occurrence of aGVHD, as well as severe and gastrointestinal aGVHD. Receiver operating characteristic (ROC) curve analysis was utilized to assess the predictive value of each biomarker. Combined analysis of CD25 and CTLA-4 mRNA levels demonstrated promising predictive potential for aGVHD.Conclusion: Our results confirmed that the transcription levels of CD25 and CTLA-4 genes could be used as early predictive biomarkers for aGVHD post-allo-HSCT.

Background: Acute graft-vs.-host disease (aGVHD) is still one of the most common and life-threatening complications of allogeneic hematopoietic stem cell transplantation (HSCT). Whether or not the level of activated T lymphocytes rises before the onset of aGVHD is unknown. We explored the possibility of T lymphocytes as biomarkers for early prediction of aGVHD in children with transfusion-dependent β-thalassemia (TDTβ).Methods: We retrospectively analyzed the characteristics of T lymphocyte subsets before and 14 days after HSCT in children with TDTβ who developed aGVHD. Data from 95 children (Age ≤ 14 years) who underwent allogeneic HSCT from January 2020 to December 2021 were collected. Patients were divided into non-aGVHD group (n = 55) and aGVHD group (n = 40), and aGVHD group was divided into two subgroups: grade I aGVHD (n = 16) and grade II-IV aGVHD (n = 24). Receiver operating characteristic curve (ROC) analysis was performed to predict aGVHD.Results: Before preconditioning in non-aGVHD and aGVHD groups, there was no significant difference in all lymphocyte subsets and ratio of CD4 + /CD8 + T cells. On day 14 post-transplantation in non-aGVHD and aGVHD groups, the absolute concentrations per μl blood of T cells, CD4 + T cells, CD8 + T cells, activated CD4 + T cell and NK cells, were 69.73 (14.70, 137.77) and 140.36 (65.06, 293.42), 10.00 (2.35, 23.59) and 35.91 (12.41, 68.71), 37.25 (5.82, 84.36) and 89.99 (35.83, 180.81), 0.52 (0.17, 2.20) and 4.08 (0.91, 11.12), 43.86 (15.00, 91.31) and 26.35 (15.19, 49.39), respectively. On day + 14 (14 days post-transplantation), the differences in all cell subsets and the ratio of CD4 + /CD8 + T cells were not statistically significant between grade I aGVHD and grade II-IV aGVHD subgroups. The absolute concentrations of CD8 + T cells in grade I aGVHD were significantly higher than in grade II-IV aGVHD [128.21 (61.11, 258.91) vs. 60.81 (21.59, 176.38), P = 0.057]. AUC of NK cells, CD8 + T cells, T cells, CD4 + T cells, and CD4 + CD25 + T cells were 0.6275, 0.6839, 0.7068, 0.7241, and 0.7589, and cut-off values were 73.75 (97.50, 34.55), 146.90 (37.50, 94.55), 187.30 (45.00, 90.91), 18.95 (70.00, 72.73), and 3.24 (52.50, 87.27), respectively. The AUC of the combined CD4 + CD25 + T cells and CD8 + T cells, CD4 + CD25 + T cells and T cells, CD4 + CD25 + T cells and CD4 + T cells, CD4 + CD25 + T cells and NK cells, respectively, were 0.7500, 0.7598, 0.7750, and 0.8050.Conclusion: Our findings demonstrate that level of activated CD4 + T cells on day + 14 (post-HSCT) is a valuable biomarker for predicting aGVHD in children with TDTβ and CD8 + T cells could likely be a biomarker for severe aGVHD.

Background: β-Thalassemia cellular immunity is associated with iron overload. However, the relationship between varying degrees of iron deposition and T cell immune recovery after allogeneic haematopoietic stem cell transplantation(allo-HSCT) in children remain unclear.Methods: A retrospective analysis was performed on 84 children with β-Thalassemia undergoing sibling allo-HSCT. According to the degrees of hepatic iron deposition, patients were divided into four classes. T lymphocyte counts were measured. Hepatic iron deposition was assessed by T2* MRI. Epstein–Barr virus and cytomegalovirus infection rates and graft-vs.-host disease incidence were recorded.Results: Immune recovery after allo-HSCT was compared between the two groups. Normal vs. mild group: CD4 cells were higher at 1, 3, and 6 months (P < 0.05), CD3 and CD8 cells were higher at 3 and 6 months, and 1 year in normal group (P < 0.05). Normal vs. moderate group: CD3 and CD4 cells were higher at 1, 3 and 6 months, and 1 year (P < 0.05), CD8 cells were higher at 1 and 3 months, and 1 year in normal group (P < 0.05). Normal vs. severe group: CD3, CD4 and CD8 cell at 1, 3 and 6 months, and 1 year in normal group (P < 0.05). Mild vs. moderate group: CD3, CD4 and CD8 cells were higher at 1 month in mild group (P < 0.05). Mild vs. severe group: CD4 cells were higher at 1, 3 and 6 month, and 1 year (P < 0.05), CD3 and CD8 cells were higher at 1 month in mild group (P < 0.05). Moderate vs. severe group: CD4 cells were higher at 3 months (P < 0.05), CD8 cells were higher at 6 months in moderate group (P < 0.05). The hepatic T2* values were positively correlated with CD3, CD4 and CD8 cells. The infection rates of Epstein-Barr virus and cytomegalovirus were significantly different among the groups (P < 0.05).Conclusion: Iron deposition affects immune recovery of T lymphocytes after allo-HSCT in children with β-thalassemia. The lower the levels of iron deposition, the greater the CD4 cell count.