血液科学(英文)最新文献

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Erratum: Development of Auer bodies from giant inclusions associated with rough endoplasmic reticulum in acute promyelocytic leukemia. 勘误:急性早幼粒细胞白血病中与粗内质网相关的巨包涵体的发育。
血液科学(英文) Pub Date : 2023-07-01 DOI: 10.1097/BS9.0000000000000163
{"title":"Erratum: Development of Auer bodies from giant inclusions associated with rough endoplasmic reticulum in acute promyelocytic leukemia.","authors":"","doi":"10.1097/BS9.0000000000000163","DOIUrl":"https://doi.org/10.1097/BS9.0000000000000163","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1097/BS9.0000000000000145.].</p>","PeriodicalId":67343,"journal":{"name":"血液科学(英文)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10400052/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9953312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Ginsenoside Rg1 improves anti-tumor efficacy of adoptive cell therapy by enhancing T cell effector functions. 人参皂苷Rg1通过增强T细胞效应物功能提高过继细胞治疗的抗肿瘤效果。
血液科学(英文) Pub Date : 2023-07-01 DOI: 10.1097/BS9.0000000000000165
Yue Liu, Lingna An, Chengfei Yang, Xiaoqi Wang, Ruihao Huang, Xi Zhang
{"title":"Ginsenoside Rg1 improves anti-tumor efficacy of adoptive cell therapy by enhancing T cell effector functions.","authors":"Yue Liu,&nbsp;Lingna An,&nbsp;Chengfei Yang,&nbsp;Xiaoqi Wang,&nbsp;Ruihao Huang,&nbsp;Xi Zhang","doi":"10.1097/BS9.0000000000000165","DOIUrl":"https://doi.org/10.1097/BS9.0000000000000165","url":null,"abstract":"<p><p>Adoptive cell therapy (ACT) has emerged with remarkable efficacies for tumor immunotherapy. Chimeric antigen receptor (CAR) T cell therapy, as one of most promising ACTs, has achieved prominent effects in treating malignant hematological tumors. However, the insufficient killing activity and limited persistence of T cells in the immunosuppressive tumor microenvironment limit the further application of ACTs for cancer patients. Many studies have focused on improving cytotoxicity and persistence of T cells to achieve improved therapeutic effects. In this study, we explored the potential function in ACT of ginsenoside Rg1, the main pharmacologically active component of ginseng. We introduced Rg1 during the in vitro activation and expansion phase of T cells, and found that Rg1 treatment upregulated two T cell activation markers, CD69 and CD25, while promoting T cell differentiation towards a mature state. Transcriptome sequencing revealed that Rg1 influenced T cell metabolic reprogramming by strengthening mitochondrial biosynthesis. When co-cultured with tumor cells, Rg1-treated T cells showed stronger cytotoxicity than untreated cells. Moreover, adding Rg1 to the culture endowed CAR-T cells with enhanced anti-tumor efficacy. This study suggests that ginsenoside Rg1 provides a potential approach for improving the anti-tumor efficacy of ACT by enhancing T cell effector functions.</p>","PeriodicalId":67343,"journal":{"name":"血液科学(英文)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10400057/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10006854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
CAR-T cell therapy in myeloma: hopes and hurdles. CAR-T细胞治疗骨髓瘤:希望与障碍。
血液科学(英文) Pub Date : 2023-04-01 DOI: 10.1097/BS9.0000000000000148
Jean Luc Harousseau
{"title":"CAR-T cell therapy in myeloma: hopes and hurdles.","authors":"Jean Luc Harousseau","doi":"10.1097/BS9.0000000000000148","DOIUrl":"https://doi.org/10.1097/BS9.0000000000000148","url":null,"abstract":"Immune therapy is a new avenue in the treatment of multiple myeloma (MM). The naked anti-38 antibodies daratumumab and isatuximab are already used in frontline therapy after excellent results have been achieved in relapsed/refractory MM (RRMM).The second step was the development of immune therapies targeting B cell maturation antigen (BCMA). Genetically mod- ified autologous chimeric antigen receptor (CAR)-T cell therapy BCMA-directed were initially tested in heavily pretreated patients with RRMM exposed to the 3 main therapeutic classes, immunomodulatory drugs (iMiDs), proteasome inhibitors, and anti-CD38 antibodies (triple-class exposed). Efficacy results were unprecedented in this context and Idecabtagene vicleucel (ide-cel or Abecma) was the first BCMA-directed CAR-T cell therapy approved in MM by both Federal Drug Administration (FDA) and European Medicines Agency (EMA). This approval was based on the results of the KarMMa Phase 2 study in 128 patients with RRMM who had previously received a median number of 6 lines of therapy (LOT). 1 The response rate (RR) was 73%, including 33% of complete response (CR) or better and 26% negative min- imal residual disease (MRD). However, median progression-free survival (PFS) was only 8.8 months. The Cartitude 1 Phase1b/2 evaluated ciltacabtagene autoleucel (cilta-cel) another CAR-T cell therapy with 2 BCMA-targeting single domain antibodies in 97 heavily pretreated patients with RRMM. 2 Results were recently updated and with a median follow-up of 27.7 months, 3 the results were even more impressive with a 98% RR, including 82.5% CR or better, and 92% negative MRD in evaluable patients. The 27-month PFS was 55%. With these results, Cilta-cel (Carvykti) was","PeriodicalId":67343,"journal":{"name":"血液科学(英文)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10205213/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9530769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Intravenous-oral itraconazole versus oral posaconazole in preventing invasive fungal diseases for acute leukemia patients. 静脉-口服伊曲康唑与口服泊沙康唑预防急性白血病侵袭性真菌疾病的比较。
血液科学(英文) Pub Date : 2023-04-01 DOI: 10.1097/BS9.0000000000000155
Li Liu, Xiaolei Pei, Runzhi Ma, Yi He, Rongli Zhang, Jialin Wei, Qiaoling Ma, Weihua Zhai, Aiming Pang, Erlie Jiang, Mingzhe Han, Donglin Yang, Sizhou Feng
{"title":"Intravenous-oral itraconazole versus oral posaconazole in preventing invasive fungal diseases for acute leukemia patients.","authors":"Li Liu,&nbsp;Xiaolei Pei,&nbsp;Runzhi Ma,&nbsp;Yi He,&nbsp;Rongli Zhang,&nbsp;Jialin Wei,&nbsp;Qiaoling Ma,&nbsp;Weihua Zhai,&nbsp;Aiming Pang,&nbsp;Erlie Jiang,&nbsp;Mingzhe Han,&nbsp;Donglin Yang,&nbsp;Sizhou Feng","doi":"10.1097/BS9.0000000000000155","DOIUrl":"https://doi.org/10.1097/BS9.0000000000000155","url":null,"abstract":"<p><p>Invasive fungal diseases (IFDs) are major and lethal infectious complications for patients with neutropenia after chemotherapy. Prophylaxis with intravenous and oral suspended itraconazole (200 mg Q12h intravenously × 2 days followed by 5 mg/kg·d orally in twice) or oral suspension of posaconazole (200 mg Q8h) was administered for preventing IFDs. The only 2 episodes of proven IFDs were not included after propensity-score matching (PSM), while the incidence of possible IFDs was 8.2% (9/110) in itraconazole group and 1.8% (2/110) in posaconazole group, respectively (<i>P</i> = .030). In clinical failure analysis, the failure rate of posaconazole group was lower as compared to the itraconazole group (2.7% vs 10.9%, <i>P</i> = .016). Both intravenous-oral itraconazole and posaconazole suspension are effective in preventing IFDs, while posaconazole suspension seems more tolerable.</p>","PeriodicalId":67343,"journal":{"name":"血液科学(英文)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10205377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9525569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Development of Auer bodies from giant inclusions associated with rough endoplasmic reticulum in acute promyelocytic leukemia. 急性早幼粒细胞白血病与粗内质网相关的巨包涵体发育成小体。
血液科学(英文) Pub Date : 2023-04-01 DOI: 10.1097/BS9.0000000000000145
Yong-Xin Ru, Shu-Xu Dong, Jing Liu, Brian Eyden
{"title":"Development of Auer bodies from giant inclusions associated with rough endoplasmic reticulum in acute promyelocytic leukemia.","authors":"Yong-Xin Ru,&nbsp;Shu-Xu Dong,&nbsp;Jing Liu,&nbsp;Brian Eyden","doi":"10.1097/BS9.0000000000000145","DOIUrl":"https://doi.org/10.1097/BS9.0000000000000145","url":null,"abstract":"<p><p>Giant inclusions and Auer bodies in promyeloblasts were investigated in a study which included transmission electron microscopy (TEM) for morphology and ultrastructural cytochemistry for myeloperoxidase in 10 patients with acute promyelocytic leukemia (APL). Ultrastructural cytochemistry demonstrated positive myeloperoxidase reactivity in giant inclusions, expanded rER cisternae, Auer bodies and primary granules. TEM revealed that giant inclusions were adorned by degenerated rER membrane, some of them sharing features with Auer bodies. We hypothesize a novel origin for Auer body development in promyeloblasts of APL, namely that they originate from peroxidase-positive and expanded rER cisternae, and that primary granules were directly released from these expanded rER elements, bypassing the Golgi apparatus.</p>","PeriodicalId":67343,"journal":{"name":"血液科学(英文)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10205345/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10299795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Big stride in gene therapy for hemophilia B in China. 血友病B基因治疗在中国取得重大进展。
血液科学(英文) Pub Date : 2023-04-01 DOI: 10.1097/BS9.0000000000000150
Jianmin Wang, Dan Yang
{"title":"Big stride in gene therapy for hemophilia B in China.","authors":"Jianmin Wang,&nbsp;Dan Yang","doi":"10.1097/BS9.0000000000000150","DOIUrl":"https://doi.org/10.1097/BS9.0000000000000150","url":null,"abstract":"In a recent issue of Lancet Haematology , Xue et al 1 reported an adeno-associated virus (AAV)-based gene therapy in 10 patients with hemophilia B (HB) from China. BBM-H901, a novel vector comprised of an engineered liver-tropic AAV cap- sid (AAV843), synthesized liver-specific promoter and CpG reduced factor IX (FIX) Padua coding sequence, was infused in 10 patients (baseline FIX coagulation activity [FIX:C] were less than 2 IU/dL) after 1 week of prophylactic prednisone pretreat- ment (1 mg/kg per day). After a median follow-up of 58 weeks, mean FIX:C reached 36.9 ± 20·5 IU/dL. No FIX inhibitors or serious adverse events were observed. All patients developed high titer neutralizing antibodies against vector capsid. The concentrations of alanine aminotransferase and aspartate aminotransferase in plasma were below the upper limit of normal range in 8 patients. No FIX concentrate infusion was needed after gene therapy for these patients. This is a huge step forward in the treatment of HB in China.","PeriodicalId":67343,"journal":{"name":"血液科学(英文)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10205292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9530768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Timing and regulation of hematopoietic stem cell colonization of the human fetal bone marrow by endothelial and CAR stromal cells during pregnancy. 妊娠期间内皮细胞和CAR基质细胞在人胎骨髓中定植造血干细胞的时间和调控。
血液科学(英文) Pub Date : 2023-04-01 DOI: 10.1097/BS9.0000000000000154
Tsvee Lapidot
{"title":"Timing and regulation of hematopoietic stem cell colonization of the human fetal bone marrow by endothelial and CAR stromal cells during pregnancy.","authors":"Tsvee Lapidot","doi":"10.1097/BS9.0000000000000154","DOIUrl":"https://doi.org/10.1097/BS9.0000000000000154","url":null,"abstract":"The bone marrow (BM) contains the major reservoir of imma- ture and maturing hematopoietic and immune cells throughout adult life while also harboring most hematopoietic stem and progenitor cells (HSPCs). BM-retained hematopoietic stem cells (HSCs) are mostly maintained in a quiescent, non-motile mode. A small fraction of BM-retained HSPC daily proliferate, differ-entiate, and migrate to the circulation, to replenish the blood with new immature and maturing blood and (all) immune (both myeloid and lymphoid) cells with a finite life span. 1 The anti-co-agulation and anti-inflammatory receptor EPCR is also func- tionally expressed by primitive BM-retained HSCs which are endowed with the highest competitive long-term repopulation potential (LT-HSC). Only BM-retained, quiescent EPCR-positive LT-HSCs are protected from DNA damaging insults includ- ing clinical chemotherapy and radiation treatments. Primitive EPCR-positive LT-HSC chemotherapy resistance requires the CXCL12-CXCR4 axis that also regulates HSC quiescence, cell cycle, and directional migration as well as the aPC/EPCR/PAR1 axis. 2,3 The chemokine CXCL12 is highly expressed by many BM endothelial and stromal cells types including HSC niche supporting osteoprogenitor cells termed CXCL12 abundant reticular cells (CAR cells), while primitive EPCR-positive fetal liver and adult BM HSC functionally express its major receptor CXCR4. 4 Most functional HSC studies involve mice experimental pre- clinical models as well as results obtained from clinical BM transplantation protocols. During fetal development, HSCs migrate from the fetal liver to the fetal BM and spleen for their lodgment","PeriodicalId":67343,"journal":{"name":"血液科学(英文)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/0a/4e/bs9-5-140.PMC10205243.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9530770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
PD-L1: expression regulation. PD-L1:表达调控。
血液科学(英文) Pub Date : 2023-04-01 DOI: 10.1097/BS9.0000000000000149
Yu-Jie Zhou, Guoli Li, Jiyin Wang, Mengyuan Liu, Zihan Wang, Yu Song, Xulong Zhang, Xi Wang
{"title":"PD-L1: expression regulation.","authors":"Yu-Jie Zhou,&nbsp;Guoli Li,&nbsp;Jiyin Wang,&nbsp;Mengyuan Liu,&nbsp;Zihan Wang,&nbsp;Yu Song,&nbsp;Xulong Zhang,&nbsp;Xi Wang","doi":"10.1097/BS9.0000000000000149","DOIUrl":"https://doi.org/10.1097/BS9.0000000000000149","url":null,"abstract":"<p><p>Programmed death-ligand 1 (PD-L1), expressed on the surface of tumor cells, can bind to programmed cell death-1 (PD-1) on T cells. The interaction of PD-1 and PD-L1 can inhibit T-cell responses by decreasing T-cell activity and accelerating their apoptosis. Various cancers express high levels of PD-L1 and exploit PD-L1/PD-1 signaling to evade T-cell immunity, and immunotherapies targeting the PD-1/PD-L1 axis have been shown to exert remarkable anti-tumor effects; however, not all tumor patients benefit from these therapies. Therefore, study of the mechanisms regulating PD-L1 expression are imperative. In this review, we explore regulation of PD-L1 expression in the contexts of gene transcription, signaling pathways, histone modification and remodeling, microRNAs, long noncoding RNAs, and post-translational modification. Current developments in studies of agents that block PD-L1 and correlations between immunotherapies targeting PD-1/PD-L1 and PD-L1 expression are also summarized. Our review will assist in understanding of PD-L1 expression regulation and discusses the implications of reported findings in cancer diagnosis and immunotherapy.</p>","PeriodicalId":67343,"journal":{"name":"血液科学(英文)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10205351/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9518329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Heterogeneity analysis of the CEBPAdm AML based on bZIP region mutations. 基于bZIP区域突变的CEBPAdm AML异质性分析。
血液科学(英文) Pub Date : 2023-04-01 DOI: 10.1097/BS9.0000000000000153
Yan Hui, Shuxin Li, Junping Zhang, Bingcheng Liu, Yingchang Mi, Hui Wei, Jianxiang Wang
{"title":"Heterogeneity analysis of the <i>CEBPA</i>dm AML based on bZIP region mutations.","authors":"Yan Hui,&nbsp;Shuxin Li,&nbsp;Junping Zhang,&nbsp;Bingcheng Liu,&nbsp;Yingchang Mi,&nbsp;Hui Wei,&nbsp;Jianxiang Wang","doi":"10.1097/BS9.0000000000000153","DOIUrl":"https://doi.org/10.1097/BS9.0000000000000153","url":null,"abstract":"<p><p>Patients with double-mutated <i>CEBPA</i> (<i>CEBPA</i>dm) AML were stratified into favorable risk group, however, few studies have investigated the heterogeneity of different <i>CEBPA</i>dm types in detail. In this study, we analyzed 2211 newly diagnosed AML and identified <i>CEBPA</i>dm in 10.8% of the patients. Within the <i>CEBPA</i>dm cohort, 225 of 239 patients (94.14%) presented with bZIP region mutations (<i>CEBPA</i>dmbZIP) while 14 of 239 patients (5.86%) without bZIP region mutation (<i>CEBPA</i>dmnonbZIP). Analysis of the accompanied molecular mutations showed statistically different incidences of GATA2 mutations between the <i>CEBPA</i>dmbZIP group and the <i>CEBPA</i>dmnonbZIP group (30.29% vs 0%). In the analysis of outcomes, patients with <i>CEBPA</i>dmnonbZIP were associated with shorter overall survival (OS) censored at hematopoietic stem cell transplantation (HSCT) during CR1 compared to those with <i>CEBPA</i>dmbZIP (hazard ratio (HR) = 3.132, 95% confidence interval (CI) = 1.229-7.979, <i>P</i> = .017). Refractory or relapsed AML (R/RAML) patients with <i>CEBPA</i>dmnonbZIP were associated with shorter OS compared to those with <i>CEBPA</i>dmbZIP (HR = 2.881, 95% CI = 1.021-8.131, <i>P</i> = .046). Taken together, AML with <i>CEBPA</i>dmbZIP and <i>CEBPA</i>dmnonbZIP showed different outcomes and might be regarded as distinctive AML entities.</p>","PeriodicalId":67343,"journal":{"name":"血液科学(英文)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10205380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9896944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
De novo myelodysplastic syndrome in a Rothmund-Thomson Syndrome patient with novel pathogenic RECQL4 variants. 新的致病性RECQL4变异的罗斯蒙-汤姆森综合征患者的新生骨髓增生异常综合征。
血液科学(英文) Pub Date : 2023-04-01 DOI: 10.1097/BS9.0000000000000152
Chuanhe Jiang, Hao Zhang, Chuxian Zhao, Luxiang Wang, Xiaoxia Hu, Zengkai Pan
{"title":"De novo myelodysplastic syndrome in a Rothmund-Thomson Syndrome patient with novel pathogenic <i>RECQL4</i> variants.","authors":"Chuanhe Jiang,&nbsp;Hao Zhang,&nbsp;Chuxian Zhao,&nbsp;Luxiang Wang,&nbsp;Xiaoxia Hu,&nbsp;Zengkai Pan","doi":"10.1097/BS9.0000000000000152","DOIUrl":"https://doi.org/10.1097/BS9.0000000000000152","url":null,"abstract":"<p><p>Rothmund-Thomson syndrome (RTS) is a rare autosomal-recessive disorder with clinical features consisting of rash, poikiloderma, sparse hair, short stature, juvenile cataracts, skeletal abnormalities, and cancer predisposition. Genetic studies involving detection of pathogenic <i>RECQL4</i> variants provide the diagnostic certitude. Osteosarcoma was found in two-thirds <i>RECQL4</i>-mutated RTS patients, while hematological malignancies were rarely reported. The variant diversity of <i>RECQL4</i> gene has not been fully identified and mutations associated with hematologic malignancies are not well described. In this study, we presented a pedigree of RTS from a Chinese family, among which the proband was diagnosed with de novo myelodysplastic syndrome (MDS). Comprehensive medical examination and chromosome karyotyping were performed on the proband. Whole exome sequencing (WES) was performed on the proband, his sister and his mother. The familial cosegregation of sequence variants derived from WES was conducted by polymerase chain reaction-based Sanger sequencing. Structures of candidate RECQL4 mutants were done by in silico analysis to assess pathogenicity. Three novel <i>RECQL4</i> germline variants, including c.T274C, c.G3014A, and c.G801C, were identified by WES and validated by Sanger sequencing. Prediction of conformation indicated that the structural stability of human RECQL4 protein was largely affected with these variants. The co-occurring <i>U2AF1</i> p.S34F and <i>TP53</i> p.Y220C mutations might contribute to the development of MDS. Our study expands the mutational spectrum of <i>RECQL4</i> and provides underlying molecular mechanism for the development of MDS in RTS patients.</p>","PeriodicalId":67343,"journal":{"name":"血液科学(英文)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/0a/7a/bs9-5-125.PMC10205365.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9530771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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