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The protein arginine methyltransferases(PRMTs)family has a wide range of molecular functions and is involved in the generation, development, proliferation and differentiation of hematopoietic cells in the stem cell development.In hematological malignancy diseases, PRMTs can be involved in many important biological processes including cell proliferation, cell cycle, gene transcription, and DNA damage repair through methylation pathways.The abnormal expression of PRMTs can lead to the occurrence and development of malignancy diseases, especially in childhood leukemia.Targeted PRMTs therapy can effectively inhibit the proliferation and survival of tumor cells by reducing the expression of PRMTs.Therefore, the relationship between PRMTs and hematological malignancy diseases has received much attention and is likely to become an important target for treatment in the future.This article reviews the role and mechanism of PRMTs in hematological malignancy diseases, in order to provide new strategies for the treatment of hematological malignancy diseases.
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Acute lymphoblastic leukemia(ALL)is the most common malignant tumor in childhood, and T-ALL accounts for 10%~15% of all in children with ALL.Based on the application of MICM classification, risk stratification and multi-drugs intensive therapy, the prognosis of children with T-ALL has been improved, but the overall survival rate and event free survival rate are still less than 70%, and the overall survival rate of relapsed / refractory T-ALL is less than 10%.The treatment of T-ALL in children still faces great challenges.CDl9 targeted chimeric antigen receptor(CAR)modified T cells have shown impressive results in children with refractory B-ALL, with remission rate of 70%~90%.The emergence of CAR-T and CAR modified NK cells(CAR-NK)targeted therapy is expected to improve the prognosis of T-ALL in children.This article reviews the latest progress of CAR-T and CAR-NK in children with T-ALL.
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Acute leukemia (AL) is the most common tumor in childhood.With the improvement of risk stratification therapy, the complete remission rate of AL has been significantly improved.However, central nervous system leukemia (CNSL) remains the major cause of recurrence and death of leukemia.This study aims to review the pathogenesis, diagnosis and treatment of CNSL in children, hoping to further improve the understanding.
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To analyze the clinical characteristics, treatment and prognosis of mediastinal germ cell tumors (GCTs) with concurrent hematologic malignancy (HM). The clinical features, treatment and prognosis of 3 cases of HM associated with mediastinal GCTs treated in the Department of Medical Oncology, Beijing Children′s Hospital from November 2014 to September 2018 were retrospectively analyzed.Meanwhile, relevant cases were searched in the PubMed and Wanfang database from their establishment to December 2019.Three male cases of HM associated with mediastinal GCTs aged from 12 to 16 years.The pathogenesis of mediastinal masses suggested teratoma or yolk sac tumor.All of them were treated with surgery and chemotherapy.Acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) was diagnosed respectively at 5 months, 9 months and 31 months after initial GCTs in the 3 cases.Two patients died and 1 child survived at the last follow-up.A total of 135 cases of concurrent GCTs and HM (or leukemia) were reviewed in online databases, involving 127 cases (94.1%) with the mediastinal GCTs associated with HM and 8 cases(5.9%) with GCTs related HM from another original sites.One hundred and twenty-six cases (99.2%) were male and the median age of GCTs diagnosis was 22 (10-48) years.Fifty-three cases (41.7%) were teratoma and 94 cases (74.0%) were GCTs containing teratoma with or without yolk sac tumor.Among the types of HM, 72 cases (56.7%) were AML and 31 cases (24.4%) were AML-M7.The median interval between GCTs and HM was 3 (0-122) months.Forty-six cases (36.2%) presented 2 malignancies simultaneously.HM were diagnosed within 12 months of GCTs in 85 cases (66.9%). The survival data were known in 107 cases, involving 94 (87.9%) deaths and 13 (12.1%) survivors.The median survival time after diagnosis of HM was 2 (0-48) months.The tendency of HM must be highly concerned in adolescent male patients with primary mediastinal GCTs, especially those with yolk sac tumor or teratoma.Their prognoses are very poor.Allogeneic hematopoietic stem cell transplantation is an alternative treatment.
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Objective:To analyze the early risk warning factors of clinical characteristics in children with acute lymphoblastic leukemia (ALL) complicated with acute pancreatitis (AP).Methods:Retrospective study.A total of 39 children with ALL complicated with AP admitted to the Hematology Center of Beijing Children′s Hospital, Capi-tal Medical University from May 2018 to December 2020 were selected as the case group, and 78 ALL patients were randomly selected as the control group according to the exact matching of 1∶2 of the same age and sex.The measurment data and counting data were analyzed by Rank sum test ( Mann Whitney U test) and χ2 test between the 2 groups, respectively, and further multivariate Logistic regression analysis was performed to find out the risk factors of ALL complicated with pancreatitis.At the same time, the relationship between each index and severity was explored. Results:The incidence of ALL complicated with AP was 8.55% (39/456 cases). The high incidence age was 3-10 years old.Sixty-four point nine percent (24/37 cases) of the pancreatitis occurred in the early stage of chemotherapy, and 66.7% (26/39 cases) was associated with asparaginase.There were significant differences in ALL risk stratification ( χ2=21.404, P<0.001), C-reactive protein (CRP)( U=232.000, P<0.001), procalcitonin (PCT)( t=3.950, P<0.001), hematocrit( t=3.981, P<0.001), serum calcium( t=-9.609, P<0.001), indirect bilirubin( U=1 142.000, P<0.05), triglyceride( t=3.600, P=0.001) and albumin( t=-6.296, P<0.001) between the 2 groups.The sensitivity of abdominal CT, abdominal ultrasound and pancreatic magnetic resonance imaging in the case group were 70.8%, 81.6% and 100.0%, respectively.Multivariate Logistic regression analysis showed that differences between albumin( OR=11.444, 95% CI: 3.240-40.423), triglyceride( OR=18.047, 95% CI: 5.020-65.074) and risk stra-tification( OR=8.894, 95% CI: 1.889-41.885) were statistically significant, and there were obvious differences in PCT( U=3.000, 2.000, all P<0.05) and serum calcium( U=4.500, 8.500, all P<0.05) between patients with severe pancreatitis and patients with mild or moderate severe pancreatitis. Conclusions:ALL complicated with AP often occurs in the early stage of chemotherapy, mainly caused by asparaginase.In imaging examination, the sensitivity of pancreatic magnetic resonance imaging is the highest, followed by abdominal ultrasound.Risk stratification, decreased albumin and elevated triglyceride are risk factors of ALL complicated with AP, which are helpful for early identification of high-risk patients with ALL complicated with AP.PCT and serum calcium may play an important role in severe pancreatitis.
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The overall survival rate of children with acute myeloid leukemia(AML) is significantly lower than that of acute lymphoblastic leukemia.The main causes of death include primary disease-related death and treatment-related death.Most of the treatment-related deaths are caused by infection, bleeding and organ failure.Infection is the most common complication of pediatric AML during the myelosuppression period after chemotherapy, and it is also the main cause of early death in AML.Based on the analysis of pathogens, laboratory tests and risk factors, this paper reviews the clinical characteristics and research progress of infection in myelosuppression following chemotherapy for AML, so as to provide a basis for early identification, clinical management and condition judgment, and further improve the survival rate of children with AML.
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The clinical data of a WHIM syndrome child with cardiac malformation as the first symptom in December 2017 in Beijing Children′s Hospital Affiliated to Capital Medical University was retrospectively analyzed.A 5-year-old female patient presented with cardiac malformation, neutropenia and recurrent infection.Heterozygous mutation(c.1000C>T) was detected in CXCR4 gene.Echocardiography and CT exhibited cardiac malformation.WHIM syndrome is very rare, and it was the first case with cardiac malformation as the first manifestation in China, thus hoping to improve clinicians′ understanding of this disease.
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Objective To discuss thk curk kffkct and sidk kffkcts of donor anti-CD19 chimkric antigkn rkckp-tor T lemphocetks(CD19 CLA-T)for trkating rkcurrknt acutk B-ckll lkuckmia aftkr allogknkic hkmatopoiktic stkm-ckll transplantation(Lllo-HSCT),and to analezk thk influkncing factors for this thkrape. Methods Thk clinical data of 5 acutk B-ckll lkuckmia patiknts wkrk analezkd rktrospkctivkle who rklapskd aftkr Lllo-HSCT and rkckivkd donor CD19 CLA-T thkrape at Bkijing Childrkn＇s Hospital from Jule 2015 to Octobkr 2017. Diskask status bkfork infusion, conditioning rkgimkn,rkinfusion ckll dosk,and sidk-kffkct of CLA-T infusion,changks in thk rklatkd immunological indicators,and follow-up trkatmknt rksults wkrk invkstigatkd. ResuIts Onk patiknt had no kffkct,othkr patiknts got rk-mission or minimal rksidual diskask(MAD)nkgativk within 4 wkkcs aftkr CLA-T infusion,and thk middlk timk was 14 daes. Pkriphkral CLA-T pkac happknkd 2 wkkcs aftkr CLA-T infusion. Be thk last follow,2 patiknts dikd of lkuckmia, 3 patiknts wkrk alivk,and 1 cask of thkm livkd with tumor aftkr CD19 nkgativk rklapsk,othkrs livkd with diskask-frkk condition. Cetocink rklkask sendromk(CAS)was thk most common sidk kffkct,happkning in 1 to 2 wkkcs aftkr infusion, 1 patiknt had nkurologic toxicitiks,and 2 patiknts had suspicious graft -vkrsus -host diskask. ConcIusions Donor CD19 CLA-T thkrape has a good short-tkrm kffkct for rklapskd B -ckll lkuckmia patiknts aftkr Lllo -HSCT,but long-tkrm kffkct rkquirks furthkr obskrvation;CAS is thk most common sidk-kffkct. Off-targkt and ckll kxhaustion ark thk main rkasons for dkfkat.
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Objective@#To observe the changes in nutrition indicators and the effect on chemotherapy complications as well as the safety of enteral nutrition by way of providing enteral nutrition support for children with acute lymphoblastic leukemia (ALL) at the stage of induction chemotherapy.@*Methods@#From November 2016 to September 2017, 60 children with newly diagnosed ALL at the Hematology Oncology Center of Beijing Children′s Hospital were enrolled in this study.They were randomly divided into an experimental group and a control group, 30 cases for each group.The experimental group was given a high-calorie diet, high-quality protein, and high-medium-chain trigly-ceride enteral nutrition on the basis of a conventional low-fat diet, and the duration lasted the whole induction treatment of ALL children; while the control group was given a low-fat diet routinely.By analyzing relevant indicators before induction chemotherapy (D0), chemotherapy day 15 (D15), and after chemotherapy (D33), the changes in nutritional status and the effect on chemotherapy complications in 2 groups were investigated.@*Results@#There was no significant difference in the body mass index (BMI) and the thickness of triceps skinfold between 2 groups before and after chemotherapy (all P>0.05). The upper arm circumference increased after chemotherapy in the experimental group[before treatment: (15.80±2.63) cm, after treatment: (16.27±2.57) cm], while that of the control group decreased slightly[before chemotherapy: (17.19±3.71) cm, after chemotherapy: (17.15±3.64) cm], and the difference between 2 groups was statistically significant (P<0.05). After chemotherapy, the total protein levels in two groups decreased[the experimental group: (64.52±4.85) g/L, the control group: (61.97±4.65) g/L] which was significantly different from that before chemotherapy [the experimental group: (68.17±6.37) g/L, the control group: (68.08±5.14) g/L] (P<0.01). The total protein level of the experimental group after chemotherapy was significant higher than that in the control group (P<0.05). Both albumin levels in 2 groups increased after chemotherapy [(42.45±4.32) g/L in the experimental group and (41.15±3.73) g/L in the control group], and there was a significant difference between 2 groups before chemotherapy [(39.54±3.26) g/L in the experimental group and (40.01±4.37) g/L in the control group] (P<0.05). The level of prealbumin increased after chemotherapy in both groups [(324.57±64.328) mg/L in the experimental group and (293.07±69.09) mg/L in the control group] compared with that before chemotherapy [(121.10±35.13) mg/L in the experimental group and(131.20±52.77) mg/L in the control group]. The change was statistically significant (P<0.01). The albumin level in the experimental group before chemotherapy was lower than that in the control group after chemotherapy, but it was higher than that in the control group after chemotherapy.Protein differences were statistically significant (P<0.05). The reduction rate of elemental iron in the experimental group after chemotherapy was lower than that in the control group, but it was not statistically significant (P>0.05). Elemental zinc was not significantly different compared with the control group.The incidence of neutropenia after chemotherapy in ALL children was higher (37/60 cases, 61.67%). The recovery of neutropenia after chemotherapy in the experimental group was better than that in the control group.After chemotherapy, the severity of anemia in the experimental group was lighter than that in the control group.The amount of blood transfusion required and amount of transfusion per capita were less than those in the control group (54 person-times vs.74 person-times, 2.45 times vs.3.08 times). The total number of transfused blood products was less than that of the control group (78 person-times vs.101 person-times), but none of the findings above were statistically significant (all P>0.05). The degree of hepatic damage in the experimental group decreased after chemotherapy, but there was no significant change in the control group.The initial activated partial thromboplastin time(APTT) prolongation in the trial group was more than that in the control group (5 cases vs.3 cases), and less than the control group (0 case vs.1 case) after chemotherapy.The frequency of fever in the experimental group during chemotherapy was less than that in the control group (6 cases vs.8 cases), and the average time of fever was shorter than that in the control group (2.8 d vs.4.1 d). None of the above findings were statistically significant (all P>0.05). During the course of chemotherapy, 0 pancreatitis occurred in the experimental group, and 1 pancreatitis occurred in the control group.There was no difference in remission rates between 2 groups of chemotherapy for 15 days and chemotherapy for 33 days.@*Conclusions@#The nutritional status of children with ALL was reduced after initial induction chemotherapy.Enteral nutrition support was helpful to maintain the nutritional status for children at the initial stage of chemotherapy, high-calorie diet, high-quality protein, and high-medium-chain triglyceride enteral nutrition support improves blood system tolerance to chemotherapy and reduces chemotherapy complications.
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Adolescent and young adult(AYA)leukemia is a typical group among the childhood leukemia.The AYA leukemia patients have not achieved the same improvements in overall survival because of their unique biological and psychological characteristics,which are often underemphasized due to the AYA patients being treated as"big child"in children′s hospital or"little adult"in adult′s hospital.Setting up a multi-disciplinary team(MDT)inclu-ding hemato-oncologists,nurses,psychologists,endocrinologists,nutritionists and pharmacologists can improve the out-come and quality of life for AYA patients with leukemia.
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Objective@#To investigate the current status of catheter-related-thrombosis (CRT) and the risk factors of Chinese acute lymphocytic leukemia (ALL) children with peripherally inserted central catheter (PICC) .@*Methods@#The clinical data of the 116 inpatients preliminarily diagnosed ALL in the Leukemia Ward of Beijing Children’s Hospital with PICC from 1st March 2014 to 31st December 2014 were collected prospectively.@*Results@#①Refer to the B-ultrasound on the 15th day after catheterization, the incidence of CRT was 28.4% (33/116 cases) , all cases were symptom-free. ②There were no statistical differences in terms of gender, age distribution, degree, immunotype between CRT and CRT-free groups. This study revealed no statistical differences of blood routine test items, coagulation function items, co-infection and catheterization vein between the two groups. While there was significant statistical difference of catheterization side, the frequency of right catheterization was higher in CRT group[75.8% (25/33) vs 55.4% (46/83) , P=0.043]. ③On the 15th day after catheterization, significant statistical difference of D-Dimer between the two groups was revealed[0.18 (0.05-2.45) mg/L vs 0.11 (0.01-5.34) mg/L, P=0.001], while no statistical differences of blood routine test items and other coagulation function items. Multivariate Logistic regression analysis verified catheterization on right was a risk factor of CRT. ④During the observation, there were 3 cases of catheter-related complications other than CRT, all of which were CRI, 2 of them had CRT meanwhile. ⑤The B-ultrasound on the 33rd day after catheterization showed that 73.1% of the cases had reduced thrombosis, 3.8% had growth thrombosis, 23.1% had no obvious change respectively.@*Conclusion@#CRT was a common catheter related complication among ALL children during induction chemotherapy, and CRT cases with symptoms were rare. Catheterization on right was a risk factor for CRT, and regular test of D-Dimer and B ultrasound contributed to detect CRT. Most of the CRT cases had reduced thrombosis without specific management.
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At present, Pediatrics textbook for international students is still in the exploring stage in China. It is necessary to make an attempt to write pediatric English textbooks by ourselves for the purpose of minimizing the gap between English original textbook and Chinese spectrum of disease, and being in accordance with teaching programs. Pediatrics English textbook should be written with excellent original English textbooks as important implications for professional resources, and adopting readable writing styles as well as multifaceted language support. Quality assurance of the textbook relies on the evaluations, and then the concrete improvement measures focusing on the significant parts of the difficulties such as author's selection, compiling style and language of textbook.
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Objective To study the current status of catheter - related thrombosis(CRT)in Chinese children through a retrospective analysis of the inpatients in the Department of Medicine,Beijing Children's Hospital Affiliated to Capital Medical University. Methods The clinical data of the inpatients with CRT from November 2010 to November 2013 were collected retrospectively,and the causes,clinical symptoms,diagnosis,treatment and prognosis were ana-lyzed. Results There were 42 cases of children with CRT in Beijing Children's Hospital Affiliated to Capital Medical University. Among the cases,the male to female ratio was 1. 0:0. 5;the median age of onset was 88(2 - 186)months with ﹤ 1 year old counted for 16. 7%(7 / 42 cases)and 13 - 14 years old counted for 11. 9%(5 / 42 cases);the distri-bution differences between the male and the female age were not significant(P = 0. 826). The median time from cathe-terization to CRT onset was 9(1 - 81)days,0 - 10 days after catheterization was the peak of onset(52. 5% ,21 / 40 ca-ses)followed by 10 - 20 days(35. 0% ,14 / 40 cases). The protopathy was usually hematologic tumor,kidney disease or deep fungal infection. Slightly more cases developed CRT on the right side(57. 1% ,24 / 42 cases)than on the left side (38. 1% ,18 / 42 cases). All cases were diagnosed by using B - ultrasound,of whom 28. 6%(12 / 42 cases)were symp-tom - free. After being diagnosed,7. 1%(3 / 42 cases)were treated with conservative methods such as immobilization of the affected limbs and hot compress;7. 1%(3 / 42 cases)had catheter removed;anticoagulant and/ or thrombolytics after catheter removal used in 33. 3% patients(14 / 42 cases). After 1 week,22 cases were reviewed,of whom 54. 5%(12 / 22 cases)had thrombosis reduced(all with intervention),thrombosis growing in 22. 7% patients(5 / 22 cases), and thrombosis did not change in 22. 7% patients(5 / 22 cases). Three cases needed re - catheterization after catheter removal,and all of 3 cases had CRT recurrences(100% ). Conclusions CRT is more common among infants and senior children. CRT usually develops within 20 days after catheterization. Children with hematologic tumor,kidney disease or deep fungal infection are more likely to have CRT. Routine ultrasound test should be conducted to monitor CRT in catheterized children. Once CRT is diagnosed,patients need to be treated with anticoagulants and/ or thrombo-lytics. Catheter should also be removed if necessary. Recatheterization can result in CRT recurrence.
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Objective To explore the common genetic abnormalities in childhood acute lymphoblastic leukemia(ALL) and their responses to early treatment response.Methods From December of 2010 to December of 2011,169 newly diagnosed ALL patients at the Department of Hematology,Beijing Children's Hospital Capital Medical University,were detected by karyotype analysis,reverse transcription polymerase chain reaction (RT-PCR) and fluorescent in situ hybridization (FISH),and the relationship between early treatment responses and genetic abnormalities was observed.Results Of the 169 cases,bone marrow cell specimens from 162 cases were successfully cultured,with the success rate reached to 95.9％,and 88 cases (52.1％) had chromosomal abnormalities.Fifty-five cases carried 8 types of fusion genes among the 153 patients who received RT-PCR examination,and the abnormal rate was 35.9％.Forty cases applied for the detection of mixed lineage leukemia (MLL) gene rearrangement by FISH,and 6 cases of them were positive.One hundred and five cases had genetic abnormalities and the detection rate reached to 62.1％ by using three combined methods.The genetic abnormalities were classified into 6 groups,they were t(12;21),t(1;19),t(9;22),MLL rearrangement,hyperdiploid and-6/6q-,-7/7q-respectively,and early therapy response in each group was compared,and statistically significant differences were found among 6 groups (x2 =22.954,19.432,14.045,P =0.001,0.001,0.016).Conclusions Conventional cytogenetics combined with RT-PCR and FISH can enhance the detection rate of genetic abnormalities in childhood ALL.Genetic abnormalities combined with early treatment response in ALL can better guide the clinical treatment and prognosis assessment.
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The multiplex gene expression genetic analysis system is a novel analytical platform,characterized by its primer design with gene-specific and universal sequences.The fluorescence capillary electrophoretic separation is used to compare and analyze the expression levels of multiplex PCR products.This technology is simple,rapid,productive and cost-effective,and holds great promise for cancer classification and biomarkers discovery.
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Objective:Previous genome-wide microarray analysis found TTCATTCT motif(DNA binding site of Runx1)in the RPL4 promoter of childhood leukemia cells,suggesting that Runx1 may regulate the expression of RPL4.This study is to investigate the relationship between Runx1 and RPL4 so as to better understand the effects of Runx1 on RPL4gene transcription,laying a foundation for further studying leukemogenesis of childhood leukemia.Methods:The luciferase plasmids containing RPL4 promoter and its mutant were constructed and were co-transfected into 293T cells with the expression plasmid of Runx1.The transactivity of RPL4 promoter was assayed by luminometer.Results:Runx1 significantly decreased the transcriptional activity of RPL4 promoter(P0.05).Conclusion:Runx1 can inhibit RPL4 gene transcription in a dose-dependent manner through binding to the TTCATTCT motif.
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Objective:To investigate the arginine (Arg) sites in splicing factor 2/alternative splicing factor (SF2/ASF) methylated by protein arginine methyltransferase 1 (PRMT1). Methods:Wild-type and Arg93,Arg97,Arg109 mutant SF2/ASF plasmids were constructed,and GST-PRMT1,GST-SF2/ASF and arginine mutant GST-SF2/ASF fusion proteins were induced and purified. Methylation activity of PRMT1 on wild-type or mutant SF2/ASF protein and methylated sites of SF2/ASF were examined by methylation assay. The effect of SF2/ASF methylation on its subcellular localization was analyzed by immunofluorescence assay.Results:PRMT1 induced methylation of SF2/ASF at arginine,and PRMT1 did not methylate SF2/ASF when SF2/ASF was mutant at Arg93,Arg97 or Arg109,with Arg97 mutation showing the most profound inhibitory effect. Methylation of SF2/ASF did not affect its subcellular localization.Conclusion:SF2/ASF is a newly identified substrate of PRMT1; Arg93,Arg97 and Arg 109 are the three methylation sites in SF2/ASF,and Arg97 is the main methylation site. Methylation of SF2/ASF does not affect its subcellular localization.