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Hemoperfusion and continuous veno-venous hemodiafiltration for eliminating chlorfenapyr in poisoning patients

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World Journal of Emergency Medicine 2024年第3期15卷 235-237页

作者： Yanqing Liu Xiaoxia Lu Haochun Wang Ming Niu Renzheng Zhang Zhongying Liu Limei Han Xiaobo Peng Xigang Zhang Poisoning Treatment Department Senior Department of Hematologythe Fifth Medical Center of PLA General HospitalBeijing 100039China

Chlorfenapyr is a liposoluble insecticide belonging to the pyrrole family.Chlorfenapyr is activated when the N-ethoxymethyl side chain breaks,forming a toxic metabolite,which uncouples oxidative phosphorylation in the mitochondria,inhibits the production of adenosine triphosphate (ATP),and leads to the death of cells and targe organisms.[1] Symptoms of chlorfenapyr poisoning in patients are mild and atypical in the early stage,especially in patients receiving low dose exposure;however,such cases are rare and may be ignored by physicians,often leading to delayed treatment.[2,3].

关键词： patients perfusion eliminating

Fc receptor-like 5(FCRL5)-directed CAR-T cells exhibit antitumor activity against multiple myeloma

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Signal Transduction and Targeted Therapy 2024年第2期9卷 724-737页

作者： Zhengyu Yu Hexian Li Qizhong Lu Zongliang Zhang Aiping Tong Ting Niu Department of hematology State Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan UniversityChengdu 610041China

Multiple myeloma(MM)remains a challenging hematologic malignancy despite advancements in chimeric antigen receptor T-cell(CAR-T)therapy.Current targets of CAR-T cells used in MM immunotherapy have limitations,with a subset of patients experiencing antigen loss resulting in relapse.Therefore,novel targets for enhancing CAR-T cell therapy in MM remain needed.Fc receptor-like 5(FCRL5)is a protein marker with considerably upregulated expression in MM and has emerged as a promising target for CAR-T cell therapeutic interventions,offering an alternative treatment for MM.To further explore this option,we designed FCRL5-directed CAR-T cells and assessed their cytotoxicity in vitro using a co-culture system and in vivo using MM cell-derived xenograft models,specifically focusing on MM with gain of chromosome 1q21.Given the challenges in CAR-T therapies arising from limited T cell persistence,our approach incorporates interleukin-15(IL-15),which enhances the functionality of central memory T(TCM)cells,into the design of FCRL5-directed CAR-T cells,to improve cytotoxicity and reduce T-cell dysfunction,thereby promoting greater CAR-T cell survival and efficacy.Both in vitro and xenograft models displayed that FCRL5 CAR-T cells incorporating IL-15 exhibited potent antitumor efficacy,effectively inhibiting the proliferation of MM cells and leading to remarkable tumor suppression.Our results highlight the capacity of FCRL5-specific CAR-T cells with the integration of IL-15 to improve the therapeutic potency,suggesting a potential novel immunotherapeutic strategy for MM treatment.

关键词： directed thereby offering

Embracing the age of artificial intelligence:paradigm shifts,opportunities,and challenges in the treatment of acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation

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Science China(Life Sciences) 2024年第6期67卷 1302-1304页

作者： Zhuo-Yu An Xiao-Hui Zhang Peking University People’s Hospital Peking University Institute of HematologyBeijing 100044China Collaborative Innovation center of hematology Peking UniversityBeijing 100044China Beijing Key Laboratory of Hematopoietic Stem Cell transplantation Beijing 100044China National Clinical Research center for Hematologic Disease Beijing 100044China

Allogeneic hematopoietic stem cell transplantation(allo-HSCT)is an important medical development in treating hematological disorders.However,the risk of acute graft-versus-host disease(a GVHD)severely limits its use.a GVHD is a severe and potentially fatal complication of alloHSCT that causes inflammation and tissue damage.It often targets the skin.

关键词： hematopoietic graft artificial

LATS1 Promotes B-ALL Tumorigenesis by Regulating YAP1 Phosphorylation and Subcellular Localization

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Current Medical Science 2024年第1期44卷 81-92页

作者： Feng ZHANG Mohammed Awal Issah Hai-ying FU Hua-rong ZHOU Ting-bo LIU Jian-zhen SHEN Fujian Provincial Key Laboratory on hematology Fujian Medical Center of HematologyFujian Institute of HematologyClinical Research Center for Hematological Malignancies of Fujian ProvinceFujian Medical University Union HospitalFuzhou 350001China Tamale Technical University Faculty of Allied Health and Pharmaceutical SciencesDepartment of Medical Laboratory TechnologyTamale NS-011-2000Ghana Department of hematology The Third Affiliated People's Hospital of Fujian University of Traditional Chinese MedicineThe Third People's Hospital of Fujian ProvinceFuzhou 350122China

Objective YAP1 plays a dual role as an oncogene and tumor suppressor gene in several tumors;differentiating between these roles may depend on the YAP1 phosphorylation pattern.The specific function of YAP1 in B cell acute lymphoblastic leukemia(B-ALL),however,is currently unclear.Thus,in the present study,the role of YAP1 in B-ALL was investigated using relevant cell lines and patient datasets.Methods The effects of shRNA-mediated knockdown on YAP1 and LATS1 levels in the NALM6 and MOLT-4 cell lines were examined using Western blotting,quantitative real-time polymerase chain reaction,flow cytometry,immunostaining,and nude mouse subcutaneous tumorigenesis experiments.Gene expression levels of Hippo pathway-related molecules before and after verteporfin(VP)treatment were compared using RNA-Seq to identify significant Hippo pathway-related genes in NALM6 cells.Results Patients with ALL showing high YAP1 expression and low YAP1-Ser127 phosphorylation levels had worse prognoses than those with low YAP1 protein expression and high YAP1-Ser127 phosphorylation levels.YAP1-Ser127 phosphorylation levels were lower in NALM6 cells than in MOLT-4 and control cells;YAP1 was distributed in the nuclei in NALM6 cells.Knockdown of YAP1 inhibited MOLT-4 and NALM6 cell proliferation and arrested the NALM6 cell cycle in the G0/G1 phase.Before and after VP treatment,the expression of the upstream gene LATS1 was upregulated;its overexpression promoted YAP1-Ser127 phosphorylation.Further,YAP1 was distributed in the plasma.Conclusion LATS1 may downregulate YAP1-Ser127 phosphorylation and maintain B-ALL cell function;thus,VP,which targets this axis,may serve as a new therapeutic method for improving the outcomes for B-ALL patients.

关键词： acute lymphoblastic leukemia large tumor suppressor kinase 1 phosphorylation RNA-Seq Yesl-associated protein

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 cases.However,no p53-targeting drugs have been approved.Here,we reposition decitabine for triple-negative breast cancer(TNBC),a subtype with frequent p53 mutations and extremely poor prognosis.In 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 TNBC.Among 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 p53.In 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 p53.In 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 TNBC.Our 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

Cross-sectional network analysis of plasma proteins/metabolites correlated with pathogenesis and therapeutic response in acute promyelocytic leukemia

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Frontiers of Medicine 2024年第2期18卷 327-343页

作者： Niu Qiao Yizhu Lyu Feng Liu Yuliang Zhang Xiaolin Ma Xiaojing Lin Junyu Wang Yinyin Xie Ruihong Zhang Jing Qiao Hongming Zhu Li Chen Hai Fang Tong Yin Zhu Chen Qiang Tian Saijuan Chen Shanghai Institute of hematology State Key Laboratory of Medical GenomicsNational Research Center for Translational Medicine at ShanghaiRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai200025China Department of hematology Second Hospital of Dalian Medical UniversityDalian116021China

The treatment of PML/RARA+acute promyelocytic leukemia(APL)with all-trans-retinoic acid and arsenic trioxide(ATRA/ATO)has been recognized as a model for translational medicine research.Though an altered microenvironment is a general cancer hallmark,how APL blasts shape their plasma composition is poorly understood.Here,we reported a cross-sectional correlation network to interpret multilayered datasets on clinical parameters,proteomes,and metabolomes of paired plasma samples from patients with APL before or after ATRA/ATO induction therapy.Our study revealed the two prominent features of the APL plasma,suggesting a possible involvement of APL blasts in modulating plasma composition.One was characterized by altered secretory protein and metabolite profiles correlating with heightened proliferation and energy consumption in APL blasts,and the other featured APL plasma-enriched proteins or enzymes catalyzing plasma-altered metabolites that were potential trans-regulatory targets of PML/RARA.Furthermore,results indicated heightened interferon-gamma signaling characterizing a tumor-suppressing function of the immune system at the first hematological complete remission stage,which likely resulted from therapy-induced cell death or senescence and ensuing supraphysiological levels of intracellular proteins.Overall,our work sheds new light on the pathophysiology and treatment of APL and provides an information-rich reference data cohort for the exploratory and translational study of leukemia microenvironment.

关键词： acute promyelocytic leukemia plasma proteomics plasma metabolomics cross-sectional correlation network pathogenesis treatment

Identification of TMEM217 as a novel prognostic biomarker and potential therapeutic target in acute myeloid leukemia

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Genes & Diseases 2024年第4期11卷 90-93页

作者： Yunying Yao Zhizhou Xi Min Wu Bo Jiao Jiaming Gao Donghe Li Xi Xie Pengfei Xu Jiaoyang Li Lei Yan Ruibao Ren Ping Liu Shanghai Institute of hematology State Key Laboratory for Medical GenomicsNational Research Center for Translational MedicineCollaborative Innovation Center of HematologyRuijin Hospital affiliated with Shanghai Jiao Tong University School of MedicineShanghai 200025China International center for Aging and Cancer Hainan Medical UniversityHaikouHainan 570102China

Despite remarkable advances in molecular and cell biology of acute myeloid leukemia(AML),AML patients still frequently relapse and have low 5-year overall survival(OS)rates.1 It is worth noting that a recent study from the registry or clinical trial compilation has reported an improvement in the OS of adult AML patients,especially those under 60 years of age.

关键词： acute myeloid leukemia

Bortezomib depended on PRDM1 and TP53 to exert therapeutic effect in activated B-cell-like diffuse large B-cell lymphoma

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Genes & Diseases 2024年第2期11卷 550-553页

作者： Jing Tang Yue Li Jiazhu Wu Haorui Shen Hua Yin Jinhua Liang Li Wang Jianyong Li Yi Xia 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

PR/SET domain 1(PRDM1)gene is located on chromosome 6q21,encoding the B lymphocyte-induced maturation protein 1(BLIMP1).1 It is reported that loss of PRDM1 function is exacerbated in activated B-cell-like(ABC)-diffuse large B cell lymphoma(DLBCL)and associated with inferior survival.However,it remains unclear what leads to PRDM1 inactivation and the drug resistance mechanism caused by abnormal inactivation of PRDM1.We investigated the contribution of PRDM1 gene as a prognosis and potential therapeutic target for ABC-DLBCL patients and further clarified the possible mechanism of PRDM1 abnormal inactivation.We first proposed that TP53 could regulate PRDM1 by histone ubiquitination modification at the post-transcriptional level.

关键词： PRDM1 TP53 therapeutic

Genotyping on circulating tumor DNA improves mutation detection rate in high-risk diffuse large B-cell lymphoma

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Genes & Diseases 2024年第4期11卷 116-119页

作者： Yi Xia Li Wang Jinhua Liang Haorui Shen Jiazhu Wu Hua Yin Yue Li Huayuan Zhu 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

Diffuse large B-cell lymphoma(DLBCL)is the most common lymphoma with heterogeneous clinical outcomes.Patients who are primarily refractory to the frontline therapy or relapse less than 12 months after diagnosis have an extremely dismal prognosis.The heterogeneous clinical outcomes of DLBCL patients result from variable genetic profiles.

关键词： lymphoma diagnosis clinical