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Integrative multi-omics and drug-response characterization of patient-derived prostate cancer primary cells

Signal Transduction and Targeted Therapy 2023年第6期8卷 3013-3028页

作者： Ziruoyu wang Yanan Li Wensi Zhao Shuai Jiang Yuqi Huang jun Hou Xuelu Zhang Zhaoyu Zhai Chen Yang Jiaqi wang Jiying zhu Jianbo Pan wei Jiang Zengxia Li Mingliang Ye Minjia Tan Haowen Jiang Yongjun Dang key laboratory of Metabolism and Molecular Medicine The Ministry of EducationDepartment of Biochemistry and Molecular BiologySchool of Basic Medical SciencesShanghai Medical CollegeFudan University200032ShanghaiChina CAS key Lab of Separation sciences for analytical chemistry National Chromatographic Research and Analysis CenterDalian Institute of Chemical PhysicsChinese Academy of Sciences116023DalianChina The Chemical Proteomics Center and state key laboratory of Drug Research Shanghai Institute of Materia MedicaChinese Academy of Sciences201203ShanghaiChina University of Chinese Academy of sciences 100049BeijingChina Department of Urology Zhongshan HospitalFudan University200032ShanghaiChina Department of Urology Zhongshan Hospital Wusong BranchFudan University200032ShanghaiChina Center for Novel Target and Therapeutic Intervention Chongqing Medical University400016ChongqingChina Department of Urology Huashan HospitalFudan University200040ShanghaiChina

Prostate cancer(PCa)is the second most prevalent malignancy in males across the world.A greater knowledge of the relationship between protein abundance and drug responses would benefit precision treatment for ***,we establish 35 Chinese PCa primary cell models to capture specific characteristics among PCa patients,including gene mutations,mRNA/protein/surface protein distributions,and pharmaceutical *** multi-omics analyses identify Anterior Gradient 2(AGR2)as a pre-operative prognostic biomarker in *** the drug library screening,we describe crizotinib as a selective compound for malignant PCa primary *** further perform the pharmacoproteome analysis and identify 14,372 significant protein-drug ***,the diminished AGR2 enhances the inhibition activity of crizotinib via ALK/c-MET-AKT axis activation which is validated by PC3 and xenograft *** integrated multi-omics approach yields a comprehensive understanding of PCa biomarkers and pharmacological responses,allowing for more precise diagnosis and therapies.

关键词： drug PC3 diagnosis operative

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Continuous observation of black carbon aerosol during winter in urban Beijing,China

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Atmospheric and Oceanic science Letters 2018年第6期11卷 491-498页

作者： XUE Peng JI Dong-Sheng AN jun-Lin CAO Wan FU Shen-Ming wei jie LI Zhi-Qing ZHOU Ying-Xing MIAO Cheng-Yuan wang Yue-Si Collaboration Innovation Center on Forecast and Evaluation of Meteorological Disasters Key Laboratory for Aerosol-Cloud-Precipitation of China Meteorological AdministrationNanjing University of Information Science and TechnologyNanjingChina state key laboratory of Atmospheric Boundary Layer Physics and Atmospheric chemistry Institute of Atmospheric PhysicsChinese Academy of SciencesBeijingChina International Center for Climate and Environment sciences Institute of Atmospheric PhysicsChinese Academy of SciencesBeijingChina key laboratory of Shale Gas and Geoengineering Institute of Geology and GeophysicsChinese Academy of SciencesBeijingChina Yunnan Wuyi Expressway Construction Headquarters YunnanKunmingChina

Black carbon(BC)has a significant impact on air quality and atmospheric light absorption due to its unique physical *** this study,a ten-wavelength black carbon monitor was used to measure BC concentrations continuously during winter in urban Beijing.A comparison of BC concentrations was carried out between the ten-wavelength black carbon monitor and a multiangle absorption photometer(MAAP)and a thermal optical transmission method carbon *** results showed significant correlations between BC measured by the MAAP,the thermal optical transmission method carbon analyzer and BC measured at the 660 nm wavelength using the ten-wavelength black carbon *** differences in BC concentrations were recorded at the different wavelength *** BC concentrations observed in the visible ranges,near-infrared ranges and near-ultraviolet ranges were on average 3.1,2.6,and 4.6μg m?3,*** differences between the absorption coefficient of BC370 nm and BC880 nm increased with the enhancement of OC:TC(ratio of organic carbon to total carbon)and PM2.5,indicating that organic matter had strong light absorption at near-ultraviolet *** concentrations had clear diurnal variations with maxima at 0300 and minima at 1400(Local time).In addition,potential contribution source areas of BC were also *** is the first time that BC measurements have been conducted using the ten-wavelength BC monitor,which provided more information of BC at different wavelengths compared to other methods.

关键词： Black carbon organic carbon Beijing absorption coefficient

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Two New Alkaloids from Fusarium tricinctum SYPF 7082,an Endophyte from the Root of Panax notoginseng

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Natural Products and Bioprospecting 2018年第5期8卷 391-396页

作者： Wen-jie Sun Hong-Tao zhu Tian-Yuan Zhang Meng-Yue Zhang Dong wang Chong-Ren Yang Yi-Xuan Zhang Ying-jun Zhang state key laboratory of Phytochemistry and Plant Resources in West China Kunming Institute of BotanyChinese Academy of SciencesKunming 650201People’s Republic of China University of Chinese Academy of sciences Beijing 100049People’s Republic of China Shenyang Pharmaceutical University Shenyang 110016People’s Republic of China Yunnan key laboratory of Natural Medicinal chemistry Kunming Institute of BotanyChinese Academy of SciencesKunmingPeople’s Republic of China

Panax notoginseng(Araliaceae)is a famous traditional Chinese medicine mainly cultivated in Yunnan and Guangxi provinces of *** new alkaloids,rigidiusculamide E(1)and[-(a-oxyisohexanoyl-N-methyl-leucyl)2-](2),together with two known ones,(-)-oxysporidinone(3)and(-)-4,60-anhydrooxysporidinone(4)were isolated from the mycelia culture of Fusarium tricinctum SYPF 7082,an endophytic fungus obtained from the healthy root of *** structures were determined on the basis of extensive spectroscopic *** 1-4 were tested for their inhibitory effects against NO production on Murine macrophage cell line,and the new compound 2 showed significant inhibitory activity on NO production with the IC_(50)value of 18.10±0.16μM.

关键词： Fusarium tricinctum SYPF 7082 Endophytic fungus Alkaloids Panax notoginseng Inhibition on NO production

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Deciphering the degradation discrepancy in Ni-rich cathodes with a diverse proportion of[003]crystallographic textures

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Carbon Energy 2023年第7期5卷 15-26页

作者： Lang Qiu Mengke Zhang Yang Song Zhenguo Wu Yan-Fang zhu jun Zhang Dong wang Hai-Yan Hu Hong-wei Li Hang-Rui Liu Xin-Bei Jia Jian Peng Shuangqiang Chen Zuguang Yang Yao Xiao Xiaodong Guo Department of Chemical Engineering College of Chemical EngineeringSichuan UniversityChengduChina Institute for Carbon Neutralization College of Chemistry and Materials EngineeringWenzhou UniversityWenzhouZhejiangChina Ruyuan Dongyang Guangcixing Material Limited CompanyShaoguanGuangdongChina Department of Chemical Engineering School of Environmental and Chemical EngineeringShanghai UniversityShanghaiChina Department of Aerospace Engineering College of Aerospace EngineeringChongqing UniversityChongqingChina state key laboratory of Electrical Insulation and Power Equipment School of Electrical EngineeringXi'an Jiaotong UniversityXi'anShaanxiChina

The crystal plane plays a very important role in the properties of Ni-rich cathodes.[003]crystallographic texture regulation has been proven to improve structural stability,and yet,the discrepancy of particles with different exposed ratios of[003]in structural attenuation has not been ***,we have unraveled comprehensively the structural decay difference for Ni-rich cathodes’primary particles with the different percentages of exposed[003]by regulating the precursor coprecipitation *** findings based on structural characterization,first-principles calculations,finite element analysis,and electrochemical test reveal that the length and width of particles represent[110]and[003]directions,respectively,and show that cathode particles with a higher[110]/[003]ratio can effectively inhibit structure degradation and intergranular/intragranular crack formation owing to the low oxygen vacancy formation energy on(003)planes and the small local stress on secondary/primary *** study may provide guidance for the structural design of layered cathodes.

关键词： cracks crystal plane Ni-rich cathodes oxygen vacancy structure degradation

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Significant loss of soil inorganic carbon at the continental scale

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National science Review 2022年第2期9卷 13-20页

作者： Xiao-Dong Song Fei Yang Hua-Yong Wu Jing Zhang De-Cheng Li Feng Liu Yu-Guo Zhao Jin-Ling Yang Bing Ju Chong-Fa Cai Biao Huang Huai-Yu Long Ying Lu Yue-Yu Sui Qiu-Bing wang Ke-Ning Wu Feng-Rong Zhang Ming-Kui Zhang Zhou Shi Wan-zhu Ma Gang Xin Zhi-Ping Qi Qing-Rui Chang En Ci Da-Gang Yuan Yang-zhu Zhang jun-Ping Bai Jia-Ying Chen jie Chen Yin-jun Chen Yun-Zhong Dong Chun-Lan Han Ling Li Li-Ming Liu Jian-jun Pan Fu-Peng Song Fu-jun Sun Deng-Feng wang Tian-wei wang Xiang-Hua wei Hong-Qi Wu Xia Zhao Qing Zhou Gan-Lin Zhang state key laboratory of Soil and Sustainable Agriculture Institute of Soil Science Chinese Academy of Sciences College of Advanced Agricultural sciences University of Chinese Academy of Sciences College of Resources and Environment Huazhong Agricultural University Institute of Agricultural Resources and Regional Planning Chinese Academy of Agricultural Sciences College of Natural Resources and Environment South China Agricultural University Northeast Institute of Geography and Agroecology Chinese Academy of Sciences College of Land and Environment Shenyang Agricultural University School of Land science and Technology China University of Geosciences College of Land science and Technology China Agricultural University College of Environmental and Resource sciences Zhejiang University Institute of Digital Agriculture Zhejiang Academy of Agricultural Sciences College of Agriculture Heilongjiang Bayi Agricultural University Tropical Crops Genetic Resources Institute Chinese Academy of Tropical Agricultural Sciences College of Natural Resources and Environment Northwest A & F University College of Resources and Environment Southwest University College of Resources Sichuan Agricultural University College of Resources and Environment Hunan Agricultural University Institute of Agricultural Product Quality Standard and Testing Research Tibet Academy of Agricultural and Animal Husbandry Sciences School of Agricultural sciences Zhengzhou University Institute of Agriculture Environment and Resources Research Shanxi Academy of Agricultural Sciences College of Resources and Environment Henan Agricultural University College of Resources and Environment China Agricultural University College of Resources and Environmental sciences Nanjing Agricultural University College of Resources and Environment Shandong Agricultural University Agricultural College Guangxi University College of Grassland and Environment science Xinjiang Agricultural University College of Geographical science Qinghai Normal University

Widespread soil acidification due to atmospheric acid deposition and agricultural fertilization may greatly accelerate soil carbonate dissolution and ***,to date,few studies have addressed these ***,we use meta-analysis and nationwide-survey datasets to investigate changes in soil inorganic carbon(SIC) stocks in *** observe an overall decrease in SIC stocks in topsoil(0-30 cm)(11.33 g C m-2yr-1) from the 1980 s to the 2010 *** SIC stocks have decreased by～8.99±2.24%(1.37±0.37 Pg C).The average SIC losses across China(0.046 Pg C yr-1) and in cropland(0.016 Pg C yr-1) account for～17.6%-24.0% of the terrestrial C sink and 57.1% of the soil organic carbon sink in cropland,*** deposition and climate change have profound influences on SIC *** estimate that～19.12%-19.47% of SIC stocks will be further lost by *** consumption of SIC may offset a large portion of global efforts aimed at ecosystem carbon sequestration,which emphasizes the importance of achieving a better understanding of the indirect coupling mechanisms of nitrogen and carbon cycling and of effective countermeasures to minimize SIC loss.

关键词： China soil inorganic carbon stocks global change carbonate soil acidification

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Neuroprotectants attenuate hypobaric hypoxia-induced brain injuries in cynomolgus monkeys

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Zoological Research 2020年第1期41卷 3-19页

作者： Pei Zhang jie-Si Chen Qi-Ye Li Long-Xiang Sheng Yi-Xing Gao Bing-Zheng Lu Wen-Bo zhu Xiao-Yu Zhan Yuan Li Zhi-Bing Yuan Gang Xu Bi-Tao Qiu Min Yan Chun-Xue Guo You-Qiong wang Yi-jun Huang Jing-Xia Zhang Fu-Yu Liu Zhong-wei Tang Sui-Zhen Lin David NCooper Huan-Ming Yang Jian wang Yu-Qi Gao wei Yin Guo-jie Zhang Guang-Mei Yan state key laboratory of Genetic Resources and Evolution Kunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650223China BGI-Shenzhen ShenzhenGuangdong 518083China Section for Ecology and Evolution Department of BiologyUniversity of CopenhagenCopenhagen DK-2100Denmark Department of Pharmacology Zhongshan School of MedicineSun Yat-Sen UniversityGuangzhouGuangdong 510080China Institute of Medicine and Hygienic Equipment for High Altitude Region College of High Altitude Military MedicineThird Military Medical UniversityChongqing 400038China key laboratory of High Altitude Medicine of People's Liberation Army Chongqing 400038China key laboratory of High Altitude Environmental Medicine Third Military Medical UniversityMinistry of EducationChongqing 400038China School of Pharmaceutical sciences Sun Yat-Sen UniversityGuangzhouGuangdong 510006China Guangzhou Cellprotek Pharmaceutical Co.Ltd. GuangzhouGuangdong 510663China Institute of Medical Genetics School of MedicineCardiff UniversityCardiff CF144XNUK James D.Watson Institute of Genome sciences HangzhouZhejiang 310058China Department of Biochemistry Zhongshan School of MedicineSun Yat-Sen UniversityGuangzhouGuangdong 510080China Center for Excellence in Animal Evolution and Genetics Chinese Academy of SciencesKunmingYunnan 650223China China National Genebank BGI-ShenzhenShenzhenGuangdong 518120China

Hypobaric hypoxia (HH) exposure can cause serious brain injury as well as life-threatening cerebral edema in severe cases. Previous studies on the mechanisms of HH-induced brain injury have been conducted primarily using non-primate animal models that are genetically distant to humans, thus hindering the development of disease treatment. Here, we report that cynomolgus monkeys (Macaca fascicularis) exposed to acute HH developed human-like HH syndrome involving severe brain injury and abnormal behavior. Transcriptome profiling of white blood cells and brain tissue from monkeys exposed to increasing altitude revealed the central role of the HIF-1 and other novel signaling pathways, such as the vitamin D receptor (VDR) signaling pathway, in co-regulating HH-induced inflammation processes. We also observed profound transcriptomic alterations in brains after exposure to acute HH, including the activation of angiogenesis and impairment of aerobic respiration and protein folding processes, which likely underlie the pathological effects of HH-induced brain injury. Administration of progesterone (PROG) and steroid neuroprotectant 5α-androst-3β,5,6β-triol (TRIOL) significantly attenuated brain injuries and rescued the transcriptomic changes induced by acute HH. Functional investigation of the affected genes suggested that these two neuroprotectants protect the brain by targeting different pathways, with PROG enhancing erythropoiesis and TRIOL suppressing glutamate-induced excitotoxicity. Thus, this study advances our understanding of the pathology induced by acute HH and provides potential compounds for the development of neuroprotectant drugs for therapeutic treatment.

关键词： Acute hypobaric hypoxia Cynomolgus monkeys Brain injury Neuroprotectant Gene regulatory networks

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Safety and efficacy of thalidomide in patients with transfusiondependentβ-thalassemia:a randomized clinical trial

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Signal Transduction and Targeted Therapy 2021年第12期6卷 3723-3729页

作者： Jiang-Ming Chen wei-Jian zhu jie Liu Gui-Zhen wang Xiao-Qin Chen Yun Tan wei-wei Xu Li-wei Qu Jin-Yan Li Huan-Ju Yang Lan Huang Ning Cai wei-Da wang Ken Huang Jian-Quan Xu Guo-Hui Li Sheng He Tian-Ying Luo Yi Huang Song-Hua Liu Wen-Qiang Wu Qi-Yang Lu Mei-Guang Zhou Shu-Ying Chen Rong-Lan Li Mei-Ling Hu Ying Huang Jin-Hua wei jun-Min Li Sai-Juan Chen Guang-Biao Zhou Department of Hematology Wuzhou Gongren HospitalWuzhou 543001 GuangxiChina Department of Hematology Zhuhai People’s Hospital(Zhuhai Hospital Affiliated with Jinan University)Zhuhai 541000 GuangdongChina state key laboratory of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of Reproductive Medicine The First Affiliated Hospital of Hebei North UniversityZhangjiakou 075000 HebeiChina state key laboratory of Oncology in South China Collaborative Innovation Center for Cancer MedicineMedical Oncology DepartmentSun Yat-Sen University Cancer CenterGuangzhou 510060 GuangdongChina state key laboratory of Medical Genomics Shanghai Institute of HematologyNational Research Center for Translational MedicineRuijin Hospital Affiliated with Shanghai Jiao Tong University School of MedicineShanghai 200025China state key laboratory of Membrane Biology Institute of ZoologyChinese Academy of Sciences&University of Chinese Academy of SciencesBeijing 100101China Department of Pediatrics Affiliated Hospital of Youjiang Medical University for NationalitiesBaise City 533000 GuangxiChina Department of Hematology Yulin Guinan HospitalYulin 537005 GuangxiChina Department of neurology Wuzhou Gongren HospitalWuzhou 543001 GuangxiChina Guangxi key laboratory of Basic Research on Birth Defects Prevention and Treatment Guangxi Zhuang Autonomous Region Women and Children Health Care HospitalNanning 530000 GuangxiChina Department of Hematology Guigang People’s HospitalGuigang 537100 GuangxiChina Department of Hematology Hospital of Traditional Chinese Medicine of Wuzhou CityWuzhou 543002 GuangxiChina Department of Hematology Wuzhou Red Cross HospitalWuzhou 543002 GuangxiChina Department of Hematology Hechi People’s HospitalHechi City 547000 GuangxiChina

Thalidomide inducesγ-globin expression in erythroid progenitor cells,but its efficacy on patients with transfusion-dependentβ-thalassemia(TDT)remains *** this phase 2,multi-center,randomized,double-blind clinical trial,we aimed to determine the safety and efficacy of thalidomide in TDT patients.A hundred patients of 14 years or older were randomly assigned to receive placebo or thalidomide for 12 weeks,followed by an extension phase of at least 36 *** primary endpoint was the change of hemoglobin(Hb)level in the *** secondary endpoints included the red blood cell(RBC)units transfused and adverse *** the placebo-controlled period,Hb concentrations in patients treated with thalidomide achieved a median elevation of 14.0(range,2.5 to 37.5)g/L,whereas Hb in patients treated with placebo did not significantly *** the 12 weeks,the mean RBC transfusion volume for patients treated with thalidomide and placebo was 5.4±5.0 U and 10.3±6.4 U,respectively(P<0.001).Adverse events of drowsiness,dizziness,fatigue,pyrexia,sore throat,and rash were more common with thalidomide than *** the extension phase,treatment with thalidomide for 24 weeks resulted in a sustainable increase in Hb concentrations which reached 104.9±19.0 g/L,without blood *** increase in Hb concentration and reduction in RBC transfusions were associated with nonβ0/β0 and HBS1L-MYB(rs9399137 C/T,C/C;rs4895441 A/G,G/G)*** results demonstrated that thalidomide is effective in patients with TDT.

关键词： transfusion patients thalidomide

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Influence of carrier gas H2 flow rate on quality of p-type GaN epilayer grown and annealed at lower temperatures

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Chinese Physics B 2018年第12期27卷 499-503页

作者： Shuang-Tao Liu Jing Yang De-Gang Zhao De-Sheng Jiang Feng Liang Ping Chen Jian-jun zhu Zong-Shun Liu wei Liu Yao Xing Li-Yuan Peng Li-Qun Zhang Wen-jie wang Mo Li state key laboratory of Integrated Optoelectronics Institute of SemiconductorsChinese Academy of SciencesBeijing 100083China College of Materials science and Opto-Electronic Technology University of Chinese Academy of SciencesBeijing 100049China Center of Materials science and Optoelectronics Engineering University of Chinese Academy of SciencesBeijing100049China Suzhou Institute of Nanotech and Nanobionics Chinese Academy of SciencesSuzhou 215123China Microsystem&Terahertz Research Center Chinese Academy of Engineering PhysicsChengdu 610200China

In this work, we study the influence of carrier gas H2flow rate on the quality of p-type GaN grown and annealed at lower temperatures. It is found that the concentration of H atoms in Mg-doped GaN epilayer can effectively decrease with appropriately reducing the carrier gas H2flow rate, and a high-quality p-type GaN layer could be obtained at a comparatively low annealing temperature by reducing the carrier gas H2flow rate. Meanwhile, it is found that the intensity and wavelength of DAP peak are changed as the annealing temperature varies, which shows that the thermal annealing has a remarkable effect not only on the activation of acceptors but also on the compensation donors.

关键词： p-type GaN thermal annealing H atom state

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Low energy range dielectronic recombination of Fluorine-like Fe^17+at the CSRm

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Chinese Physics C 2018年第6期42卷 53-58页

作者： Nadir Khan Zhong-Kui Huang wei-Qiang Wen Sultan Mahmood Li-jun Dou Shu-Xing wang Xin Xu Han-Bing wang Chong-Yang Chen Xiao-Ya Chuai Xiao-Long zhu Dong-Mei Zhao Li-jun Mao jie Li Da-Yu Yin Jian-Cheng Yang You-Jin Yuan Lin-Fan zhu Xin-Wen Ma Institute of Modern Physics Chinese Academy of Sciences Lanzhou 730000 China University of Chinese Academy of sciences Beijing 100049 China Hefei National laboratory for Physical sciences at Micro Scale Department of Modern Physics University of Science and Technology of China Hefei 230026 China Shanghai EBIT laboratory Key Laboratory of Nuclear Physics and Ion-beam Application Institute of Modern Physics Department of Nuclear Science and Technology Fudan University Shanghai 200433 China

The accuracy of dielectronic recombination （DR） data for astrophysics related ions plays a key role in astrophysical plasma modeling. The absolute DR rate coefficient of Fe^17＋ ions was measured at the main cooler storage ring at the Institute of Modern Physics, Lanzhou, China. The experimental electron-ion collision energy range covers the first Rydberg series up to n = 24 for the DR resonances associated with the 2p1/2 →^2 p3/2△n= 0 core excitations. A theoretical calculation was performed by using FAC code and compared with the measured DR rate coefficient. Overall reasonable agreement was found between the experimental results and calculations. Moreover, the plasma rate coefficient was deduced from the experimental DR rate coefficient and compared with the available results from the literature. At the low energy range, significant discrepancies were found, and the measured resonances challenge state-of-the-art theory at low collision energies.

关键词： storage ring electron cooler electron-ion recombination plasma rate coefficient

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FIPIL1-PDGFRα alone or with other genetic abnormalities reveals disease progression in chronic eosinophilic leukemia but good response to imatinib

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Chinese Medical Journal 2008年第10期121卷 867-873页

作者： wang Lin-na PAN Qin FU Jian-fei SHI Jing-yi JIN jie LI jun-ming HU Jion ZHAO wei-li CHEN zhu CHEN Sai-juan state key laboratory of Medical Genomics Shanghai institute of Hematology Shanghai Ruijin Hospital Shanghai Jiao TongUniversity School Of Medicine Shanghai 200025 China Zhejiang Institute of Hematology First Affiliated HospitalZhejiang University School of Medicine Hangzhou Zhejiang 310003 China

Background The FIP1L1-PDGFRa fusion gene plays an important role in the pathogenesis of chronic eosinophilic leukemia （CEL） and is a direct therapeutic target of the tyrosine kinase inhibitor imatinib mesylate. Methods In 24 hypereosinophilic syndromes （HES） patients, using reverse transcriptase-polymerase chain reaction （RT-PCR）, nested PCR and sequence analysis, we investigated the frequency of FIPIL1-PDGFRa and other abnormalities of tyrosine kinase family genes like PDGFRa, PDGFRβ, C-KIT, FGFR1, ABL and FLT3 as well as gene mutation ＂hotspots＂, like MPL515 and JAK2V617F, frequently involved in myeloproliferative diseases. Fluorescence in situ hybridization was used to confirm the 4q 12 deletion. Results The FIP1L1-PDGFRa fusion transcript was found in 8 （33%） of 24 patients with HES, corresponding to the chromosome 4q12 deletion identified by FISH. The FIP1L 1-PDGFRα-associated patients diagnosed with CEL, frequently had hepatosplenomegaly, eosinophil-related tissue damage, anemia, thrombocytopenia, myelofibrosis and a short overall survival time. Nevertheless, imatinib mesylate induced rapid and complete hematological responses in treated FIP1L1-PDGFRa cases, followed by molecular remission and reversal of myelofibrosis. FIP1L1-PDGFRa fusion could co-exist with other mutations of tyrosine kinase family genes, like FLT3 or PDGFRβ. We also demonstrated that the SNPs of PDGFRβ were associated with selective splicing of exon 19 in case 20. Conclusions Correlating the CEL genotype with phenotype, FIP1L1-PDGFRa emerges as a relatively homogeneous clinicobiological entity that co-exists with other abnormalities of tyrosine kinase family genes. It reflects the disease progression and there is a good response to imatinib. Detection of the FIP1L 1-PDGFFla fusion gene is valid for both CEL diagnosis and therapy surveillance.

关键词： chronic eosinophilic leukemia FIP1L1-PDGFRa tyrosine kinase imatinib mesylate myeloproliferative disease

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