Acute lymphoblastic leukemia after rhabdomyosarcoma caused by germline TP53 mutation: a case report and literature review / 中华实用儿科临床杂志

Objective:To understand the hereditary cancer related to germline TP53 mutations. Methods:A retrospective analysis was performed on a case of acute lymphoblastic leukemia(ALL) secondary to rhabdomyosarcoma admitted to Wuhan Children′s Hospital in February 2019.The clinical characteristics and gene detection were analyzed, and the correlative literature was studied.Results:The patient was diagnosed with rarely pleomorphic rhabdomyosarcoma at the age of 9 months, and only underwent complete excision without subsequent chemotherapy and radiotherapy.Seven years later, without exposure to suspicious carcinogenic risk factors, she was suffered from secondary ALL, germline TP53 mutations were confirmed by mutation gene detection and genetic verification.She received the induction treatment with Vincristine+ Daunorubicin+ L-Asparaginase+ Dexamethasone(VDLD), and then achieved the complete remission.According to the literature review result, there were 1 438 mutations emerging in TP53 gene, which were dominant by missense point mutations (707 kinds). These mutations could result in early-onset tumors that commonly arose in female patients.Molecular targeted therapy through TP53 gene mutation pathway could resist tumors. Conclusions:Germline TP53 mutation screening should be recommended for the early-onset tumor with genetic predisposition, and systematical monitoring of the family is also suggested, so as to early intervene and prevent the occurrence of the second tumor.The targeted drugs for germline TP53 mutations can reduce the toxicity of radiotherapy and chemotherapy and achieve high treatment effects.

Gene mutation associated with hemophagocytic lymphohistiocytosis in children / 临床儿科杂志

Objectives To detect gene mutation associated with hemophagocytic lymphohistiocytosis (HLH) and to identify mutation spectrum and clinical feature in HLH in children. Methods Thirty-seven (37) pediatric patients diagnosed with HLH according to 2004 clinical and laboratory criteria were enrolled from July 2012 to November 2015. Nucleotide sequences of all exons and their flanking intronic sequences of ten genes associated with HLH were amplified with PCR followed by direct sequencing. Point mutation analysis was performed after the direct sequencing. Results The median age of all the 37 patients was 2.6 years. The median ages of patients with gene mutation (n=22) and without gene mutation (n=15) was 2.09 years and 2.67 years, without statistical significance. Twenty-two patients were identified with gene mutations. All of them were heterozygous. UNC13D mutation (50%) is of the highest frequency in the above genes. The splicing mutations (38%) were the main type of UNC13D mutations,and missense mutations or frame-shift mutations were also found. There was no statistical difference in ages of onset and laboratory data of neutrophils, thrombocytes, NK cell activities within the three groups: multi-site mutations, single-site mutations and no mutations. EBV infection was detected in 70.3% patients. In mutation group, one patient died when he was in the period of inducing remission, and four patients were relapsed. Among them four patients were infected with EBV and one patients was negative at the onset while positive in recurrence. Conclusions UNC13D was the predominant causative gene in the Chinese population according our data. There was no significant relevance between age of onset, severity of disease and gene mutations. Attention should be paid to a patient with HLH gene mutation infected by EBV, which it might mean a poor prognosis.

Correlation of Serum Calprotectin Expression with Clinical Response in Juvenile Idiopathic Arthritis Patients Treated with a Tumor Necrosis Factor Inhibitor / 中国医科大学学报

Objective To investigate the correlation of serum calprotectin (MRP8/14) expression with clinical response in Chinese juvenile idiopathic arthritis (JIA) patients treated with a tumor necrosis factor (TNF) inhibitor.Methods Seventy-two JIA patients and 30 health volunteers (HCs) were enrolled in this prospective study.All JIA patients received etanercept for 24 weeks.Serum was collected from JIA patients at baseline before treatment and from HCs.Clinical response was defined according to the American College of Rheumatology (ACR) Pedi 50 criteria.Results Serum MRP8/14 expression was greater in JIA patients than in HCs (P ＜ 0.001).Serum MRP8/14 level was greater in responders than in non-responders (area under the receiver operating characteristic curve,0.823;95％ CI:0.706-0.939).Univariate and multivariate logistic analysis showed that high serum MRP8/14 expression was an independent predictive factor for clinical response (P =0.003).Conclusion Serum MRP8/14 level can be used as a convincing and novel biomarker for clinical response in JIA patients treated with a TNF inhibitor.