Abstract Purpose:: Multiple myeloma(MM) is a common malignant tumor in the blood system. Despite recent advances in its treatment, its symptomatic remission rate and survival rate are still not optimistic. In the future, it is necessary to continue to search for different treatment targets and new treatment methods in order to improve the quality of life and survival time of patients with MM. The study aims to explore the potential immune related pivotal genes and immune infiltration patterns in MM. Methods: The study included peripheral blood samples from patients with MM who our hospital from October 2020 to April 2022. Obtain a gene chip for research from a comprehensive gene expression database, perform differential expression analysis on the processed gene dataset, and then perform functional enrichment analysis, weighted gene co expression network analysis, GSEA immune infiltration analysis, and LASSO regression analysis on the obtained differential expression genes to obtain the hub genes. Finally, the hub gene TNFSF14 (LIGHT) was validated by qRT-PCR. Results: In the study, three immune-related hub genes (ADAM8, CR2, and TNFSF14) and three main types of peripheral immune cells (activated CD8 T cells, macrophages, and plasma cell like dendritic cells) were obtained, which are closely related to the pathogenesis of MM. Then, by collecting peripheral blood samples from some patients in our hospital and conducting real-time fluorescence quantitative polymerase chain reaction, it was confirmed that the hub gene TNFSF14 (LIGHT) mined in this study was highly expressed in peripheral blood samples from patients with MM, which may indicate that it plays a pathogenic role in MM. Conclusion: The study found that immune-related hub genes (ADAM8, CR2, and TNFSF14) are closely related to the pathogenesis of MM, and should be further researched.
Abstract Purpose:: Multiple myeloma(MM) is a common malignant tumor in the blood system. Despite recent advances in its treatment, its symptomatic remission rate and survival rate are still not optimistic. In the future, it is necessary to continue to search for different treatment targets and new treatment methods in order to improve the quality of life and survival time of patients with MM. The study aims to explore the potential immune related pivotal genes and immune infiltration patterns in MM. Methods: The study included peripheral blood samples from patients with MM who our hospital from October 2020 to April 2022. Obtain a gene chip for research from a comprehensive gene expression database, perform differential expression analysis on the processed gene dataset, and then perform functional enrichment analysis, weighted gene co expression network analysis, GSEA immune infiltration analysis, and LASSO regression analysis on the obtained differential expression genes to obtain the hub genes. Finally, the hub gene TNFSF14 (LIGHT) was validated by qRT-PCR. Results: In the study, three immune-related hub genes (ADAM8, CR2, and TNFSF14) and three main types of peripheral immune cells (activated CD8 T cells, macrophages, and plasma cell like dendritic cells) were obtained, which are closely related to the pathogenesis of MM. Then, by collecting peripheral blood samples from some patients in our hospital and conducting real-time fluorescence quantitative polymerase chain reaction, it was confirmed that the hub gene TNFSF14 (LIGHT) mined in this study was highly expressed in peripheral blood samples from patients with MM, which may indicate that it plays a pathogenic role in MM. Conclusion: The study found that immune-related hub genes (ADAM8, CR2, and TNFSF14) are closely related to the pathogenesis of MM, and should be further researched.
Objective:To explore the efficacy and safety of unrelated mismatched hematopoietic stem cell transplantation(HSCT)for thalassemia major.Methods:For this retrospective cohort study, 15 patients with β-thalassemia major underwent unrelated mismatched HSCT between January 2018 and April 2022. There were 8 males and 7 females with a median age of 7(3-12)years and a median ferritin level of 3 417.3(223-14 485)μg/L. The conditioning regimens on the basis of fludarabine(Flu), busulfan(Bu)and cyclophosphamide(CTX)and GVHD prophylaxis on the basis of cyclosporine(CsA), mycophenolate mofetil(MMF), anti-human thymocyte immunoglobulin(ATG)plus low-dose post-cyclophosphamide(PTCy)and mesenchymal stem cells were offered.Results:Up until April 1, 2022, 15 children were successfully implanted during a median follow-up period of 24.1(11-49)months and all of them achieved stable donor chimerism. The median time to neutrophil and platelet engraftment were 12(11-22)and 14(8-38)days respectively. Except for 2 deaths, 13 cases survived. The estimated 2-year probability of overall survival(OS)and thalassemia-free survival(TFS)were both 86.67%. There were 5 cases of acute graft versus host disease (aGVHD) below grade Ⅱ, 2 cases of grade Ⅲ to Ⅳ aGVHD, and 3 cases of localized chronic graft versus host disease (cGVHD) after transplantation. No gengralized cGVHD occurred. Both cytomegalovirus and Epstein-Barr virus were activated in five recipients.Conclusions:Unrelated mismatched donor HSCT is both safe and feasible for thalassemia major.
OBJECTIVE:To investigate the clinical correlation of expression level changes of miR-181b and miR-194 to the pathogenesis of acute graft-versus-host disease (aGVHD), and determine plasma miR-181b and miR-194 as the potential biomarkers for aGVHD. METHODS:The plasma samples were collected from 31 patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) at before HSCT, 15 days after HSCT and onset of aGVHD. The expression levels of miR-181b and miR-194 were detected by quantitative real-time PCR. Receiver-operating characteristic (ROC) curves and the area under the ROC curve (AUC) were used to assess the sensitivity and specificity of miRNA biomarkers for the diagnosis of aGVHD. RESULTS:MiR-181b and miR-194 downregulated after treatment were significantly upregulated in the plasma at onset of aGVHD (P<0.05), and there was no significant difference in comparison with the level of before HSCT (P>0.05). The expressions of plasma miR-181b and miR-194 collected on day 15 after HSCT were significantly upregulated in the patients with aGVHD in comparison with non-GVHD patients (P<0.05). Moreover, these elevated miRNAs were detected before aGVHD. The AUC of miR-181b predicting aGVHD was 0.91±0.05 (specificity was 0.94, sensitivity was 0.69). The AUC of miR-194 predicting aGVHD was 0.91±0.06 (specificity was 0.94, sensitivity was 0.77). CONCLUSION:MiR-181b and miR-194 may serve as early biomarkers for the diagnosis and prognosis of aGVHD.
背景:异基因造血干细胞移植后纯红细胞再生障碍性贫血的发生导致患者红系造血恢复延迟、血型转换时间延长,从而产生一系列并发症.因此,应重视异基因造血干细胞移植后纯红细胞再生障碍性贫血预防和诊断后的治疗对策,以加快移植后红系植入.目前纯红细胞再生障碍性贫血的发生率、高危因素尚无定论,诊疗尚无规范指南.目的:探讨异基因造血干细胞移植后纯红细胞再生障碍性贫血发病的高危因素和治疗对策.方法:2例患者,诊断为急性白血病,接受同胞供者的清髓性外周血干细胞移植,供受者血型均为A供O,分别于+44 d、+58 d出现纯红细胞再生障碍性贫血,复习诊治过程和相关文献.结果与结论:①1例经美罗华、大剂量甲强龙、血浆置换治疗后痊愈;另1例经大剂量甲强龙、美罗华和硼替佐米治疗后血象于5个月后逐渐恢复;②总结文献报道的93例发生移植后纯红细胞再生障碍性贫血病例,所有患者均为供受者ABO血型不合,明确血型的患者中A供O者占66%(47/71),同胞供者、非清髓预处理、病毒感染等是发生纯红细胞再生障碍性贫血的高危因素,主要治疗方法有血浆置换、激素、利妥昔单抗等;③异基因造血干细胞移植后纯红细胞再生障碍性贫血是少见的并发症,多种因素可促进其发生,目前尚无一致的治疗共识,部分患者可以自愈,对难治性患者,硼替佐米和艾曲波帕可作为新的靶向治疗药物.