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Decitabine in combination with idarubicin within a modified busulfan/cyclophosphamide conditioning regimen for patients with advanced myelodysplastic syndrome:A prospective multicenter clinical cohort study

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Chinese Medical Journal 2024年第9期137卷 1115-1117页

作者： Yigeng Cao Mingyang Wang Fuxu Wang Wenwen Guo Yueshen Ma Xiaoyun Li Yi He Aiming Pang Rongli Zhang Weihua Zhai Xin Chen Qiaoling Ma Jialin Wei Donglin Yang Yong Huang Dan Feng Jia Liu Xin Gao Shupeng Wen Wen Wang Tao Wang Ying Li Xiaosheng Fang Yingchun Li Xiaohan Zhang Yun Cai Yongqi Wang Weijie Cao Runqing Lu Sizhou Feng Rong Guo Yuewen Fu Xin Du Zhuogang Liu Xin Wang Ling Wang Liangming Ma Chuanfang Liu Xuejun Zhang Mingzhe Han Erlie Jiang department of Hematopoietic Stem Cell Transplantation Center State Key Laboratory of Experimental HematologyNational Clinical Research Center for Blood DiseasesHaihe Laboratory of Cell EcosystemInstitute of HematologyBlood Diseases HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300000China department of hematology Second Hospital of Hebei Medical UniversityHebei Key Laboratory of HematologyShijiazhuangHebei 050000China Center for Information and Resource State Key Laboratory of Experimental HematologyNational Clinical Research Center for Blood DiseasesHaihe Laboratory of Cell EcosystemInstitute of HematologyBlood Diseases HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300000China department of hematology Qilu Hospital of Shandong UniversityJinanShandong 250000China department of hematology Shanxi Bethune HospitalThird Hospital of Shanxi Medical UniversityTaiyuanShanxi 030032China department of hematology Qingdao Central HospitalUniversity of Health and Rehabilitation SciencesQingdaoShandong 266042China department of hematology Shandong Provincial HospitalCheeloo College of MedicineShandong UniversityJinanShandong 250000China department of hematology Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinanShandong 250000China department of hematology Shengjing Hospital of China Medical UniversityShenyangLiaoning 110000China department of hematology Shenzhen Second People’s HospitalThe First Affiliated Hospital of Shenzhen UniversityShenzhen University School of MedicineShenzhenGuangdong 518000China department of hematology Henan Cancer HospitalCancer Hospital Affiliated Zhengzhou UniversityZhengzhouHenan 450000China department of hematology Department of HematologyThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450000China

To the Editor:Allogeneic hemopoietic stem cell transplantation(allo-HSCT)represents the only long-term survival treatment choice for patients with myelodysplastic syndromes(MDS)and MDS/myeloproliferative neoplasm(MPN).Unfortunately,post-hemopoietic stem cell transplantation(HSCT)relapse remains a cause of treatment failure and the results of salvage treatments are *** better conditioning regimens is urgently *** studies have shown synergistic antileukemic effects between decitabine(DEC)and idarubicin(IDA).[1]In an attempt to design a conditioning strategy with very low toxicity but considerable myelosuppressive activity and potential immune-enhancing effects for patients with high-risk MDS and MDS/MPN,we combined DEC and IDA with busulfan,cyclophosphamide,andudarabine for a modied myeloablative regimen in this prospective,multicenter cohort study(hereafter referred to as the“DEC/IDA study”).

关键词： regimen myelo patients

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Haploidentical hematopoietic cell transplantation with or without an unrelated cord blood unit for adult acute myeloid leukemia:a multicenter,randomized,open-label,phase 3 trial

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2669-2678页

作者： Biqi Zhou Jia Chen Tianhui Liu Yishan Ye Yanming Zhang Yiyang Ding Hong Liu MingQing Zhu Xiao Ma Xiaoli Li Longfei Zhao Zhihong Lin He Huang Yang Xu Depei Wu National Clinical Research Center for Hematologic Diseases Jiangsu Institute of HematologyThe First Affiliated Hospital of Soochow UniversitySuzhouChina institute of Blood and Marrow Transplantation Collaborative Innovation Center of HematologySoochow UniversitySuzhouChina Bone Marrow Transplantation Center The First Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiangChina department of hematology The Affiliated Huai’an Hospital of Xuzhou Medical University and The Second People’s Hospital of Huai’anHuai’anChina Soochow Hopes hematology Hospital SuzhouChina department of hematology Hygeia Suzhou Yongding HospitalSuzhouChina

Coinfusion of unrelated cord blood(UCB)units in haploidentical hematopoietic cell transplantation(haplo-HCT)(haplo-cord HCT)for hematopoietic malignancies showed promising results in previous reports,but the efficiency of haplo-cord HCT in acute myeloid leukemia(AML)still lacks sufficient *** multicenter,randomized,phase 3 trial(*** NCT03719534)aimed to assess the efficacy and safety of haplo-cord HCT in AML patients.A total of 268 eligible patients aged 18-60 years,diagnosed with measurable residual disease in AML(excluding acute promyelocytic leukemia),with available haploidentical donors and suitable for allotransplantation,were randomly allocated(1:1)to receive haplo-cord HCT(n=134)or haplo-HCT(n=134).The 3-year overall survival(OS)was the primary endpoint in this *** median follow-up was 36.50 months(IQR 24.75-46.50).The 3-year OS of Haplo-cord HCT group was better than haplo-HCT group(80.5%,95%confidence interval[CI]:73.7-87.9 vs.67.8%95%CI 60.0-76.5,p=0.013).Favorable progression-free survival(70.3%,95%CI 62.6-78.8 vs.57.6%,95%CI 49.6-67.0,p=0.012)and cumulative incidence of relapse(12.1%,95%CI 12.0-12.2 vs.30.3%,95%CI 30.1-30.4,p=0.024)were observed in haplo-cord HCT *** 3-4 adverse events(AEs)within two years posttransplantation in the two groups were ***-cord HCT patients exhibited a faster cumulative incidence of neutrophil recovery(p=0.026)and increased T-cell reconstitution in the early period ***-cord HCT can improve OS in AML patients without excessive AEs,which may exert additional benefits for recipients of haplo-HCT.

关键词： hematopoietic acute phase

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Ginsenoside Rd Induces Differentiation of Myeloid Leukemia Cells via Regulating ERK/GSK-3βSignaling Pathway

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Chinese Journal of Integrative Medicine 2024年第7期30卷 588-599页

作者： JIANG Yu-xia ZHAO Yan-na YU Xiao-ling YIN Li-ming department of hematology Tongde Hospital of Zhejiang ProvinceHangzhou310012China institute of hematology Research the First Affiliated Hospital of Zhejiang Chinese Medical University(Zhejiang Provincial Hospital of Chinese Medicine)Hangzhou310006China

Objective To investigate the role of ginsenoside Rd(GRd)in acute myeloid leukemia(AML)cell *** AML cells were treated with GRd(25,50,100 and 200µg/mL),retinoic acid(RA,0.1g/L)and PD98059(20 mg/mL)for 72 h,cell survival was detected by methylthiazolyldiphenyl-tetrazolium bromide and colony formation assays,and cell cycle was detected by flow *** morphology and differentiation were observed by Wright-Giemsa staining,peroxidase chemical staining and cellular immunochemistry assay,*** protein expression levels of GATA binding protein 1(GATA-1),purine rich Box-1(PU.1),phosphorylated-extracellular signal-related kinase(p-ERK),ERK,phosphorylated-glycogen synthase kinase-3β(p-GSK3β),GSK3βand signal transducer and activator of transcription 1(STAT1)were detected by Western ***-six mice were randomly divided into 3 groups using a random number table:model control group(non-treated),GRd group[treated with 200 mg/(kg·d)GRd]and homoharringtonine(HTT)group[treated with 1 mg/(kg·d)HTT].A tumor-bearing nude mouse model was established,and tumor weight and volume were *** of subcutaneous tumor tissue were observed after hematoxylin and eosin ***1 and GATA-1 expressions were detected by immunohistochemical *** The cell survival was inhibited by GRd in a dose-dependent manner and GRd caused G0/G1 cell arrest(p<0.05).GRd treatment induced leukemia cell differentiation,showing increased expressions of peroxidase and specific proteins concerning erythrogenic or granulocytic differentiation(p<0.05).GRd treatment elicited upregulation of p-ERK,p-GSK-3βand STAT1 expressions in cells,and reversed the effects of PD98059 on inhibiting the expressions of peroxidase,GATA-1 and PU.1(P<0.05).After GRd treatment,tumor weight and volume of mice were decreased,and tumor cells underwent massive apoptosis and necrosis(P<0.05).WT1 level was decreased,and GATA-1 level was significantly increased in subcutaneous tumor ti

关键词： ginsenoside Rd myeloid leukemia survival differentiation extracellular signal-related kinase signaling pathway

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Analysis of the role of dihydromyricetin derived from vine tea(Ampelopsis grossedentata)on multiple myeloma by activating STAT1/RIG-I axis

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Oncology Research 2024年第8期32卷 1359-1368页

作者： WEI JIANG MEI ZHOU department of hematology Shaoxing Shangyu People’s HospitalShaoxing312000China department of hematology Zhuji People’s HospitalShaoxing311800China

Multiple myeloma(MM)is a plasma cell malignancy and remains incurable as it lacks effective curative approaches;thus,novel therapeutic strategies are desperately *** study aimed to explore the therapeutic role of dihydromyricetin(DHM)in MM and explore its *** MM and normal plasma samples,human MM cell lines,and normal plasma cells were used for in vitro *** counting kit-8(CCK-8),flow cytometry,and trans-well assays were performed for the assessment of cell viability,apoptosis,migration,and invasion,*** real-time polymerase chain reaction(qRT-PCR)was employed to assess the mRNA expression of signal transducer and activator of transcription 1(STAT1)and retinoic acid-inducible gene I(RIG-I).Western blotting was employed to assess E-cadherin,N-cadherin,signal transducer,STAT1,p-STAT1,and RIG-I protein expression.A tumor xenograft model was used for in vivo ***,dihydromyricetin(DHM)dose-dependently restrained viability,apoptosis,migration,and invasion,and facilitated apoptosis of U266 *** DHM treatment,the Ecadherin level was increased and the N-cadherin level was decreased in U266 and RPMI-8226 cells,suggesting the inhibitory effects of DHM on epithelial-mesenchymal transition(EMT)in ***,the levels of p-STAT1/STAT1 and RIG-I were down-regulated in ***,the STAT1 inhibitor fludarabine undid the suppressive effect of DMH on the malignant characteristics of U266 ***,DHM inhibited MM tumor growth and EMT,and activated STAT1/RIG-I pathway in ***,this study first revealed that DHM can restrain EMT and tumor growth in MM by activating STAT1/RIG-I signaling,which provides a novel drug for the treatment of MM.

关键词： Dihydromyricetin Multiple myeloma Epithelial-mesenchymal transition Tumor growth

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Current situation and development of hematopoietic cell transplantation centers:A nationwide survey in China

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Chinese Medical Journal 2024年第13期137卷 1626-1628页

作者： Yi Fan Mimi Xu Yuqing Tu Yu Hu Qifa Liu Weili Zhao Xiaohui Zhang Zimin Sun Ting Niu Jianda Hu Juan Li Lin Liu Li Liu Sanbin Wang Sujun Gao Yongrong Lai Xianmin Song Zhenyu Li Jingbo Wang Zhongxing Jiang Yajing Xu Jinsong Yan Pengcheng He Jianmin Yang Jia Chen Yang Xu Xiaojun Huang Depei Wu On behalf of the National Clinical Research Center for Hematologic Diseases(NCRCH)at Suzhou National Clinical Research Center for Hematologic Diseases The First Affiliated Hospital of Soochow UniversityJiangsu Institute of HematologySuzhouJiangsu 215000China department of hematology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430022China department of hematology Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdong 510510China State Key Laboratory of Medical Genomics Shanghai Institute of HematologyNational Research Center for Translational MedicineShanghai Rui Jin HospitalShanghai Jiao Tong University School of MedicineShanghai 215200China department of hematology Peking University People’s HospitalPeking University Institute of HematologyPeking UniversityBeijing 100044China department of hematology The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui 230001China department of hematology West China HospitalSichuan UniversityChengduSichuan 610041China department of hematology Fujian Medical University Union HospitalFuzhouFujian 350001China department of hematology The First Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 510080China department of hematology The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400042China department of hematology Tangdu HospitalFourth Military Medical UniversityXi’anShaanxi 710038China department of hematology General Hospital of Kunming Military Region of the People’s Liberation Army(PLA)KunmingYunan 650100China department of hematology and Oncology Bethune First Hospital Of Jilin UniversityChangchunJilin 130021China department of hematology The First Affiliated Hospital of Guangxi Medical UniversityGuilinGuangxi 530021China department of hematology Shanghai General HospitalShanghai 201620China department of hematology The Affiliated Hospital of Xuzhou Medical UniversityXuzhouJiangsu 221004China department of hematology Aerospace Center HospitalBei

To the Editor:Hematopoietic cell transplantation(HCT)is a vital modality to cure severe hematological disorders.[1]Global or regional summarized data of HCT are annually reported by the Chinese Blood and Marrow Transplantation Registry Group(CBMTRG),European Society for Blood and Marrow Transplantation(EBMT)and Center for International Blood and Marrow Transplant Research(CIBMTR).It is shown that the number of transplants is continuously increasing,particularly in China in recent years.[2]Since the donor accessibility is significantly addressed by the well-established protocol of haplo-identical HCT(haplo-HCT).

关键词： Blood hematopoietic centers

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Chidamide plus prednisone,cyclophosphamide,and thalidomide for relapsed or refractory peripheral T-cell lymphoma:A multicenter phase II trial

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Chinese Medical Journal 2024年第13期137卷 1576-1582页

作者： Jinhua Liang Li Wang Xiaodong Wang Guohui Cui Jianfeng Zhou Tongyao Xing Kaixin Du Jingyan Xu Luqun Wang Rong Liang Biyun Chen Jian Cheng Haorui Shen Jianyong Li Wei Xu department of hematology The First Affiliated Hospital of Nanjing Medical UniversityJiangsu Province HospitalNanjingJiangsu 210029China Key Laboratory of hematology of Nanjing Medical University NanjingJiangsu 210029China Collaborative Innovation Center for Cancer Personalized Medicine NanjingJiangsu 210029China department of hematology Sichuan Academy of Medical Sciences&Sichuan Provincial People’s HospitalSchool of Medicine of University of Electronic Science and Technology of ChinaChengduSichuan 610000China department of hematology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430022China department of hematology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430030China department of hematology Nanjing Drum Tower HospitalNanjing University Medical SchoolNanjingJiangsu 210008China department of hematology Qilu Hospital of Shandong UniversityJinanShandong 250000China department of hematology Xijing HospitalThe Fourth Military Medical UniversityXi’anShaanxi 710032China department of hematology Fujian Provincial HospitalFuzhouFujian 350001China department of hematology Zhongda HospitalMedical School of Southeast UniversityNanjingJiangsu 210009China

Background:Although the treatment of peripheral T-cell lymphoma(PTCL)has undergone advancements during the past several years,the response rate and long-term effects with respect to patients with PTCL remain unsatisfactory—particularly for relapsed or refractory(R/R)*** phase II trial was designed to explore the efficacy and safety of an all-oral regimen of chidamide plus prednisone,cyclophosphamide,and thalidomide(CPCT)for R/R PTCL patients who could not tolerate the standard chemotherapy for a variety of ***:We conducted a multicenter phase II clinical trial in which we combined chidamide(30 mg twice weekly)with prednisone(20 mg daily after breakfast),cyclophosphamide(50 mg daily after lunch),and thalidomide(100 mg daily at bedtime)(the CPCT regimen)for a total of fewer than 12 cycles as an induction-combined treatment period,and then applied chidamide as single-drug ***-five patients were ultimately enrolled from August 2016 to April 2021 with respect to Chinese patients at nine *** primary objective was to assess the overall response rate(ORR)after the treatment with ***:Of the 45 enrolled patients,the optimal ORR and complete response(CR)/CR unconfirmed(CRu)were 71.1%(32/45)and 28.9%(13/45),respectively,and after a median follow-up period of 56 months,the median progression-free survival(PFS)and overall survival(OS)were 8.5 months and 17.2 months,*** five-year PFS and OS rates were 21.2%(95%confidence interval[CI],7.9-34.5%)and 43.8%(95%CI,28.3-59.3%),*** most common adverse event was neutropenia(20/45,44.4%),but we observed no treatment-related ***:The all-oral CPCT regimen was an effective and safe regimen for R/R PTCL patients who could not tolerate standard chemotherapy for various *** Registration:***,NCT02879526.

关键词： Peripheral T-cell lymphoma Chidamide Prednisone Cyclophosphamide Thalidomide All-oral regimen

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Waldenström macroglobulinemia:a challenging case treated with anti-CD19 CAR-T cell therapy

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第8期25卷 719-722页

作者： Yang YANG Xiaolin GU Jingsong HE Yongxian HU Zhen CAI Bone Marrow Transplantation Center Department of Hematologythe First Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhou 310006China department of hematology Putuo People’s HospitalZhoushan 316100China

Waldenström macroglobulinemia(WM)is characterized by lymphoplasmacytic lymphoma associated with large amounts of monoclonal immunoglobulin M(IgM)protein(Owen et al.,2003).Common signs and symptoms include fatigue due to anemia,lymph node enlargement,hepatosplenomegaly,thrombocytopenia,symptoms related to high viscosity,and peripheral neuropathy,among *** significant advances in WM treatment,this type of indolent lymphoma remains incurable,with a wide array of patient outcomes(Ruan et al.,2020).In recent years,chimeric antigen receptor T(CAR-T)cell therapy targeting cluster of differentiation 19(CD19)has shown unprecedented response rates and durability in the treatment of B-cell *** this report,we describe a challenging case of WM that involved multiple extramedullary sites,relapsed,and was refractory to chemotherapy,immunotherapy,and targeted *** anti-CD19 CAR-T cell therapy,the tumor burden significantly decreased and the patient’s condition remained stable at the writing of this report.

关键词： CD19 globulin durability

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SENEX-mediated CDK4/6 inhibition promotes senescence and confers apoptosis resistance in B-cell non-Hodgkin lymphoma

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BIOCELL 2024年第3期48卷 453-462页

作者： JIYU WANG LIUYING YI KEKE HUANG YANGYANG WANG HUIPING WANG ZHIMIN ZHAI department of hematology The Second Affiliated Hospital of Anhui Medical UniversityHefei230601China department of hematology The Fourth Affiliated HospitalZhejiang University School of MedicineYiwu322000China

Background:The primary cause of treatment failure in patients with refractory or relapsed B-cell non-Hodgkin lymphoma(r/r B-NHL)is resistance to current therapies,and therapy-induced senescence(TIS)stands out as a crucial mechanism contributing to tumor drug ***,we analyzed SENEX/Rho GTPase Activating Protein 18(ARHGAP18)expression and prognostic signiﬁcance in doxorubicin-induced B-NHL-TIS model and r/r B-NHL patients,investigating its target in B-NHL cell senescence and the effect of combining speciﬁc inhibitors on apoptosis resistance in B-NHL-TIS ***:Raji cells were transfected with the human SENEX shRNA recombinant lentiviral vector(Sh-SENEX)and the empty vector negative(NC)to construct a stable transfection cell line with knockdown of *** of SENEX-silencing on B-NHL-TIS formation,cell function and cell cycle-related pathways was *** doxorubicin(DOX)-inducible senescent B-NHL cells combined with the speciﬁc cyclin dependent kinase 4/6(CDK4/6)inhibitor Palbociclib to observe that blocking CDK4/6 effects on TIS *** expression of 21 B-NHL patients and 8 healthy controls were analyzed by qRT-PCR,and the correlation between its expression and clinical indicators were ***:The downregulation of SENEX expression promotes G1-S phase transition and apoptosis while inhibiting cell proliferation,collectively suppressing the formation of TIS in *** of CDK4/6 promotes the DOX-induced G1 phase arrest to enhance TIS formation in B-NHL cells which can reverse the regulatory effect of silencing SENEX on B-NHL cell cycle regulation and *** expression levels of SENEX were notably elevated in B-NHL patients compared to healthy controls,and Elevated expression levels of SENEX were associated with poor prognosis of B-NHL ***:SENEX enhances apoptosis resistance in B-NHL by inhibiting CDK4/6,thereby preventing G1-S phase transition and promoting TIS formation.

关键词： SENEX B-cell non-Hodgkin lymphoma CDK4/6 G1-S phase transition Therapy-induced senescence Apoptosis resistance

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Immune cells in the B-cell lymphoma microenvironment:From basic research to clinical applications

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Chinese Medical Journal 2024年第7期137卷 776-790页

作者： Wenli Zhang Mengmeng Liu Wei Li Yongping Song department of hematology The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450052China department of hematology Henan Provincial Hematology HospitalZhengzhouHenan 450000China Academy of Medical Sciences Zhengzhou UniversityZhengzhouHenan 450052China department of Research and Foreign Affairs The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer HospitalZhengzhouHenan 450008China

B-cell lymphoma is a group of hematological malignancies characterized by variable genetic and biological features and clinical *** tumor microenvironment(TME)is a complex network in tumors,which consists of surrounding blood vessels,extracellular matrix,immune and non-immune cells,and signaling *** evidence has shown that the TME,especially immune cells within,is a double-edged sword,acting either as a tumor killer or as a promoter of tumor *** pro-tumor activities are driven by subpopulations of immune cells that express typical markers but have unique transcriptional characteristics,making tumor-associated immune cells good targets for human anti-cancer therapy by ablating immunosuppressive cells or enhancing immune-activated ***,exploring the role of immune cells in the TME provides distinct insights for immunotherapy in B-cell *** this review,we elucidated the interaction between immune cells and tumor cells and their function in the initiation,progression,and prognosis of B-cell lymphoma,from preclinical experiments to clinical ***,we outlined potential therapeutic approaches and discussed the potential clinical value and future perspectives of targeting immune cells in patients with B-cell lymphoma.

关键词： Tumor microenvironment B-cell lymphoma Immune cells Immunotherapy Targeted therapy

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Decitabine induces IRF7-mediated immune responses in p53-mutated triple-negative breast cancer:a clinical and translational study

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Frontiers of Medicine 2024年第2期18卷 357-374页

作者： Haoyu Wang Zhengyuan Wang Zheng Wang Xiaoyang Li Yuntong Li Ni Yan Lili Wu Ying Liang Jiale Wu Huaxin Song Qing Qu Jiahui Huang Chunkang Chang Kunwei Shen Xiaosong Chen Min Lu department of General Surgery Comprehensive Breast Health CenterRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai200025China Shanghai institute of hematology State Key Laboratory of Medical GenomicsNational Research Center for Translational Medicine(Shanghai)Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai200025China department of hematology Shanghai Institute of HematologyRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai200025China department of hematology Shanghai Jiao Tong University Affiliated Sixth People’s HospitalShanghai200025China

p53 is mutated in half of cancer ***,no p53-targeting drugs have been ***,we reposition decitabine for triple-negative breast cancer(TNBC),a subtype with frequent p53 mutations and extremely poor *** a retrospective study on tissue microarrays with 132 TNBC cases,DNMT1 overexpression was associated with p53 mutations(P=0.037)and poor overall survival(OS)(P=0.010).In a prospective DEciTabinE and Carboplatin in TNBC(DETECT)trial(NCT03295552),decitabine with carboplatin produced an objective response rate(ORR)of 42%in 12 patients with stage IV *** the 9 trialed patients with available TP53 sequencing results,the 6 patients with p53 mutations had higher ORR(3/6 vs.0/3)and better OS(16.0 vs.4.0 months)than the patients with wild-type *** a mechanistic study,isogenic TNBC cell lines harboring DETECT-derived p53 mutations exhibited higher DNMT1 expression and decitabine sensitivity than the cell line with wild-type *** the DETECT trial,decitabine induced strong immune responses featuring the striking upregulation of the innate immune player IRF7 in the p53-mutated TNBC cell line(upregulation by 16-fold)and the most responsive patient with *** integrative studies reveal the potential of repurposing decitabine for the treatment of p53-mutated TNBC and suggest IRF7 as a potential biomarker for decitabine-based treatments.

关键词： p53 mutation triple-negative breast cancer decitabine DNMT1 IRF7 innate immune response

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