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REDH:A database of RNA editome in hematopoietic differentiation and malignancy

Chinese Medical Journal 2024年第3期137卷 283-293页

作者： Jiayue Xu Jiahuan He Jiabin Yang Fengjiao Wang Yue Huo Yuehong Guo Yanmin Si Yufeng Gao Fang Wang Hui Cheng Tao Cheng Jia Yu Xiaoshuang Wang Yanni Ma State Key Laboratory of Common Mechanism Research for Major Diseases Haihe Laboratory of Cell EcosystemInstitute of Basic Medical SciencesChinese Academy of Medical SciencesBeijing 100005China Key Laboratory of RNA and hematopoietic Regulation Chinese Academy of Medical SciencesBeijing 100005China Department of Biochemistry and Molecular Biology Chinese Academy of Medical SciencesSchool of Basic Medicine Peking Union Medical CollegeBeijing 100005China State Key Laboratory of Experimental Hematology National Clinical Research Center for Blood DiseasesInstitute of Hematology and Blood Diseases HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeTianjin 300020China Institute of Blood Transfusion Chinese Academy of Medical SciencesChengduSichuan 610052China

Background:The conversion of adenosine(A)to inosine(I)through deamination is the prevailing form of RNA editing,impacting numerous nuclear and cytoplasmic transcripts across various eukaryotic *** of high-confidence RNA editing sites have been identified and integrated into various RNA databases,providing a convenient platform for the rapid identification of key drivers of cancer and potential therapeutic ***,the available database for integration of RNA editing in hematopoietic cells and hematopoietic malignancies is still ***:We downloaded RNA sequencing(RNA-seq)data of 29 leukemia patients and 19 healthy donors from National Center for Biotechnology Information(NCBI)Gene Expression Omnibus(GEO)database,and RNA-seq data of 12 mouse hematopoietic cell populations obtained from our previous research were also *** performed sequence alignment,identified RNA editing sites,and obtained characteristic editing sites related to normal hematopoietic development and abnormal editing sites associated with hematologic ***:We established a new database,"REDH",represents RNA editome in hematopoietic differentiation and *** is a curated database of associations between RNA editome and *** integrates 30,796 editing sites from 12 murine adult hematopoietic cell populations and systematically characterizes more than 400,000 edited events in malignant hematopoietic samples from 48 cohorts(human).Through the Differentiation,Disease,Enrichment,and knowledge modules,each A-to-I editing site is systematically integrated,including its distribution throughout the genome,its clinical information(human sample),and functional editing sites under physiological and pathological ***,REDH compares the similarities and differences of editing sites between different hematologic malignancies and healthy ***:REDH is accessible at http://***/.This user-friendly database

关键词： RNA editing hematopoietic differentiation hematopoietic malignancy Database management systems

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Impact of payment source, referral site, and place of residence on outcomes after allogeneic transplantation in Mexico

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World Journal of Transplantation 2024年第2期14卷 76-87页

作者： Andrés Gómez-De León Yesica A López-Mora Valeria García-Zárate Ana Varela-Constantino Sergio U Villegas-De Leon Xitlaly J González-Leal Raúl del Toro-Mijares Anna C Rodríguez-Zúñiga Juan F Barrios-Ruiz Victor Mingura-Ledezma Perla R Colunga-Pedraza Olga G Cantú-Rodríguez César H Gutiérrez-Aguirre Luz Tarín-Arzaga Elías E González-López David Gómez-Almaguer Hematology Service Universidad Autónoma de Nuevo LeónFacultad de Medicina y Hospital Universitario Dr.JoséEleuterio GonzálezMonterrey 64460Nuevo LeónMexico Hemato-logy Service Clínica Gómez AlmaguerMonterrey 64710Nuevo LeónMexico Hematology Service Instituto Tecnológico de Estudios Superiores de MonterreyTec SaludEscuela de Medicina Ignacio SantosMonterrey 64710Nuevo LeónMexico

BACKGROUND The impact of social determinants of health in allogeneic transplant recipients in low-and middle-income countries is poorly *** observational study analyzes the impact of place of residence,referring institution,and transplant cost coverage(out-of-pocket vs government-funded vs private insurance)on outcomes after allogeneic hematopoietic stem cell transplantation(alloHSCT)in two of Mexico's largest public and private *** To evaluate the impact of social determinants of health and their relationship with outcomes among allogeneic transplant recipients in *** In this retrospective cohort study,we included adolescents and adults≥16 years who received a matched sibling or haploidentical transplant from *** were selected without regard to their diagnosis and were sourced from both a private clinic and a public University Hospital in *** payment groups were compared:Out-of-pocket(OOP),private insurance,and a federal Universal healthcare program“Seguro Popular”.Outcomes were compared between referred and institution-diagnosed patients,and between residents of Nuevo Leon and *** outcomes included overall survival(OS),categorized by residence,referral,and payment *** outcomes encompassed early mortality,event-free-survival,graft-versus-host-relapse-free survival,and non-relapse-mortality(NRM).Statistical analyses employed appropriate tests,Kaplan-Meier method,and Cox proportional hazard regression *** software included SPSS and R with tidycmprsk *** Our primary outcome was overall *** included 287 patients,n=164 who lived out of state(57.1%),and n=129 referred from another institution(44.9%).The most frequent payment source was OOP(n=139,48.4%),followed by private insurance(n=75,26.1%)and universal coverage(n=73,25.4%).No differences in OS,event-free-survival,NRM,or graft-versus-host-relapse-free survival were observed for patients dia

关键词： hematopoietic cell transplant Social determinants of health Geography Haploidentical Out-of-pocket Financial toxicity Survival Health services and outcomes hematopoietic malignancy Aplastic anemia

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Three-year Follow-up on the Safety and Effectiveness of Rituximab Plus Chemotherapy as First-Line Treatment of Diffuse Large B-Cell Lymphoma and Follicular Lymphoma in Real-World Clinical Settings in China： A Prospective, Multicenter, Noninterventional Study

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Chinese Medical Journal 2018年第15期131卷 1767-1775页

作者： Jian-Qiu WU Yong-Ping Song Li-Ping Su Ming-Zhi Zhang Wei Li Yu Hu Xiao-Hong Zhang Yu-Huan Gao Zuo-Xing Niu Ru Feng Wei Wang Jie-Wen Peng Xiao-Lin Li Xue-Nong Ouyang Chang-Ping Wu Wei-Jing Zhang Yun Zeng Zhen Xiao Ying-Min Liang Yong-Zhi Zhuang Ji-Shi Wang Zi-Min Sun Hai Bai Tong-Jian Cui Ji-Feng Feng Department of Oncology Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & Nanjing Medical University Affiliated Cancer Hospital Nanjing Jiangsu 210008 China Department of Hematology Henan Cancer Hospital Zhengzhou Henan 450000 China Department of Hematology Shanxi Cancer Hospital Taiyuan Shanxi 030013 China Department of Oncology The First Affiliated Hospital of Zhengzhou University Zhengzhou Henan 450000 China Department of Oncology Jilin University First Affiliated Hospital Changchun Jilin 130000 China Department of Hematology Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan Hubei 430072 China Department of Hematology The Second Affiliated Hospital of Zhejiang University School of Medicine Hangzhou Zhejiang 310009 China Department of Hematology Fourth Hospital of Hebei Medical University Shijiazhuang Hebei 050000 China Department of Oncology Affiliated Hospital of Shandong Academy of Medical Sciences Jinan Shandong 250000 China Department of Hematology Medical University Nanfang Hospital Guangzhou Guangdong 510000 China Department of Oncology Guangdong Foshan First Hospital Foshan Guangdong 528000 China Department of Oncology Guangdong Zhongshan People's Hospital Zhongshan Guangdong 528403 China Department of Hematology Xiangya Hospital Central South University Changsha Hunan 410008 China Department of Oncology Fuzhou General Hospital of Nanjing Military Command Fuzhou Fujian 350001 China Department of Oncology Changzhou First People's Hospital Changzhou Jiangsu 213000 China Department of Oncology 307 Hospital of Chinese People's Liberation Army Beijing 100070 China TDepartment of Hematology First Affiliated Hospital of Kunming Medical University Kunming Yunnan 650221 China Department of Hematology Affiliated Hospital of Neimenggu Medical College Hohhot Huhehaote Inner Mongolia 010050 China Department of Hematology The Fourth Military Medical University Affiliated Tangdu Hospital X

Background： Prospective real-life data on the safety and effectiveness of rituximab in Chinese patients with diffuse large B-cell lymphoma （DLBCL） or follicular lymphoma （FL） are limited. This real-world study aimed to evaluate long-term safety and effectiveness outcomes ofrituximab plus chemotherapy （R-chemo） as first-line treatment in Chinese patients with DLBCL or FL. Hepatitis B virus （HBV） reactivation management was also investigated. Methods： A prospective, multicenter, single-arm, noninterventional study of previously untreated CD20-positive DLBCL or FL patients receiving first-line R-chemo treatment at 24 centers in China was conducted between January 17, 2011 and October 31, 2016. Enrolled patients underwent safety and effectiveness assessments after the last rituximab dose and were followed up for 3 years. Effectiveness endpoints included progression-free survival （PFS） and overall survival （OS）. Safety endpoints were adverse events （AEs）, serious AEs, drug-related AEs, and AEs of special interest. We also reported data on the incidence of HBV reactivation. Results： In total, 283 previously untreated CD20-positive DLBCL and 31 FL patients from 24 centers were enrolled. Three-year PFS was 59% （95% confidence interval [CI]： 50-67%） for DLBCL patients and 46% （95% CI： 20-69%） for FL patients. For DLBCL patients, multivariate analyses showed that PFS was not associated with international prognostic index, tumor maximum diameter, HBV infection status, or number ofrituximab treatment cycles, and OS was only associated with age 〉60 years （P 〈 0.05）. R-chemo was well tolerated. The incidence of HBV reactivation in hepatitis B surface antigen （HBsAg）-positive and HBsAg-negative/hepatitis B core antibody-positive patients was 13% （3/24） and 4% （3/69）, respectively. Conclusions： R-chemo is effective and safe in real-world clinical practice as first-line treatment for DLBCL and FL in China, and that HBV reactivation during R-chemo is manageable with preventive measur

关键词： Asian hematopoietic malignancy Hepatitis B Virus Observational Study Rituximab

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NEW DRUG TARGETING TREATMENT-GLIVEC

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Chinese Journal of Cancer Research 2003年第3期15卷 235-239页

作者：孙雪梅 BRADY Ben Nanjing Drum Tower Hospital Nanjing University Medical College Nanjing 210008 China The Cabrini Medical Center Victoria 3050 Australia

This review evaluates the role of Glivec in the treatment of chronic myelogenous leukemia and other malignant tumors. Preclinical and clinical evidence showed that Glivec demonstrated a potent and specific inhibition on BCR-ABL positive leukemias and other malignant tumors in which overexpression of c-kit and PDGFR-b played a major role in their pathogenesis. Glivec has induced complete hematologic responses in up to 98% of patients evaluated in clinical trials. It's a very successful drug that supported the idea of targeted therapy through inhibition of tyrosine kinases. Although it's still in the early stages of clinical development and the resistance to Glivec remains to be a problem needed further study, a great deal has been learned from these research and observation. And with the increasing data, molecular targeting therapy will play much more important role in the treatment of malignant tumors. With the better understanding of the pathogenesis of malignant tumors, well-designed drugs targeting the specific molecular abnormalities with higher efficacy and lower side effect will benefit numerous patients with malignant tumors.

关键词： Protein tyrosine kinase Glivec ST1571 Targeting therapy hematopoietic malignancy BCR-ABL c-kit PDGFR-b

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ABNORMAL PROTEIN TYROSINE KINASES ASSOCIATED WITH HUMAN HAEMATOLOGICAL MALIGNANCIES

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Chinese Journal of Cancer Research 2002年第2期14卷 79-83页

作者：孙雪梅 Graham J Lieschke The Affiliated Drum Tower Hospital Nanjing University Nanjing 210008 ChinaLudwig Institute for Cancer Research The Royal Melbourne Hospital Victoria 3050 Australia Ludwig Institute for Cancer Research The Royal Melbourne Hospital Victoria 3050 Australia

Objective: To survey the role of protein tyrosine kinases (PTKs) in the pathogenesis of several hematopoietic malignancies. Methods: By reviewing the published laboratory and clinical studies on PTK-related oncoproteins and their causative role in some leukemias and lymphomas. Results: Protein tyrosine kinases are key participants in signal transduction pathways that regulate cellular growth, activation and differentiations. Aberrant PTK activity resulting from gene mutation (often accompanying chromosome translocation) plays an etiologic role in several clonal hematopoietic malignancies. For example, the PTK product of the BCR-ABL fusion gene resulting from the t (9; 22) translocation exhibits several fold higher tyrosine kinase activity than the product of the ABL gene. Evidence suggests that the BCR-ABL oncoprotein alone is sufficient to case chronic myelogenous leukemia (CML) and other Ph positive acute leukemia. PTK over-activity resulting from chromosomal translocations creating TEL-ABL, TEL-JAK2 and TEL-PDGFRβ fusion proteins plays an important role in the pathogenesis of other types of leukemia. Another example occurs in anaplastic large cell lymphoma (ALCL). Experimental and clinical evidences indicate that translocations involving ALK gene on chromosome 2p23, most commonly resulting in an NPM-ALK fusion oncogene, result in constitutive activation of ALK and cause ALCL. This group of lymphomas is now named ALK positive lymphoma or ALKoma. Conclusion: Genetic lesions creating aberrant fusion proteins that result in excessive PTK activity are increasingly being recognized as central to the pathogenesis of hemotopoietic malignancies. These chimeric PTK molecules represent attractive disease-specific targets against which new classes therapeutic agents are being developed.

关键词： Protein tyrosine kinase (PTK) hematopoietic malignancy BCR-ABL Chronic myelogenous leukemia (CML) Anaplastic large cell lymphoma (ALCL) STI 571 Protein tyrosine kinase inhibitor

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Myeloid-derived suppressor cells inhibit T cell proliferation in extranodal NK/T-cell lymphoma: a novel prognostic indicator

Myeloid-derived suppressor cells inhibit T cell proliferatio...

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第十届全国免疫学学术大会

作者： Han Zhang Jiang Li Sun Yat-Sen University Cancer Center

Object:We aimed at detecting the frequency of MDSCs in the peripheral blood of ENKL patients to characterize the phenotypic and functional features of MDSCs in ENKL,and we further assessed its clinical significance and prognostic ***:Peripheral blood mononuclear cells(PBMCs)were collected from 32 age-matched healthy donors and 32 patients with ENKL at the first time of diagnosis at Sun Yat-Sen University Cancer Center(Guangzhou,China)from July2010 to December *** statistical analysis was performed with the SPSS 13.0 software(SPSS,Chicago,IL,USA)or Graph Pad Prism analysis tools(La Jolla,CA,USA).Results:A higher percentage of circulating HLA-DR-CD33+CD11b+MDSCs was observed in ENKL patients than in healthy controls(P60%)and CD15+granulocytic(PMN-MDSCs,<20%)***,these ENKL-MDSCs expressed higher levels of Arg-1,i NOS and IL-17 compared to the levels of MDSCs from healthy donors,and they expressed moderate levels of TGF-βand IL-10 but lower levels of ***,based on multivariate Cox regression analysis,the HLA-DR-CD33+CD11b+cells and CD14+Mo-MDSCs were independent predictors for disease-free survival(DFS,P=0.013 and 0.016)and overall survival(OS,P=0.017 and 0.027).Conclusion:Our results revealed an expansion of circulating MDSCs in ENKL patients;these ENKL-MDSCs mainly consist of CD14+Mo-MDSCs and express high levels of i NOS,Arg-1 and suppressive cytokines including IL-10,TGF-βand ***,increases in circulating MDSCs and Mo-MDSCs correlate with poor DFS and OS in patients,and they are independent predictors in ***,these findings demonstrate a novel role and mechanism of MDSCs in the tumor pathogenesis of ENKL,thus unveiling a new avenue for ENKL immunotherapy.

关键词： Prognosis Immunosuppression hematopoietic malignancy MDSC NK/T-cell lymphoma

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