Objective:To explore the application of genetic abnormalities in the diagnosis of angioimmunoblastic T-cell lymphoma(AITL)and the reliable pathological prognostic factors.Methods:This study included 53 AITL cases,whic...Objective:To explore the application of genetic abnormalities in the diagnosis of angioimmunoblastic T-cell lymphoma(AITL)and the reliable pathological prognostic factors.Methods:This study included 53 AITL cases,which were reviewed for morphological patterns,immunophenotypes,presence of Hodgkin and Reed-Sternberg(HRS)-like cells,and co-occurrence of B cell proliferation.The Epstein-Barr virus(EBV)-positive cells in tissues were counted,and cases were classified into“EBV encoded RNA(EBER)high-density”group if>50/HPF.Targeted exome sequencing was performed.Results:Mutation data can assist AITL diagnosis:1)with considerable HRS-like cells(20 cases):RHOA mutated in 14 cases(IDH2 co-mutated in 3 cases,4 cases with rare RHOA mutation),TET2 was mutated in 5 cases(1 case comutated with DNMT3A),and DNMT3A mutated in 1 case;2)accompanied with B cell lymphoma(7 cases):RHOA mutated in 4 cases(1 case had IDH2 mutation),TET2 mutated in 2 cases and DNMT3A mutated in 1 case;3)mimic peripheral T cell lymphoma,not otherwise specified(5 cases):RHOA mutated in 2 cases(IDH2 co-mutated in 1 case),TET2 mutated in 3 cases,and DNMT3A mutated in 1 case;4)pattern 1(1 case),RHOA and TET2 co-mutated.Besides RHOAG17V(30/35),rare variant included RHOAK18N,RHOAR68H,RHOAC83Y,RHOAD120G and RHOAG17del,IDH2R172 co-mutated with IDH2M397V in one case.There were recurrent mutations of FAT3,PCLO and PIEZO1 and genes of epigenetic remodeling,T-cell activation,APC and PI3K/AKT pathway.EBER high-density independently indicated adverse overall survival and progression-free survival(P=0.046 and P=0.008,KaplanMeier/log-rank).Conclusions:Over half AITL cases might be confused in diagnosis for certain conditions without mutation data.Targeted exome sequencing with a comprehensive panel is crucial to detect both hot-spot and rare mutation variants for RHOA and IDH2 and other recurrent mutated genes in addition to TET2 and DNMT3A.EBER highdensity independently indicated adverse survival.展开更多
Imaging flow cytometry(IFC)combines the imaging capabilities of microscopy with the high throughput of flow cytometry,offering a promising solution for high-precision and high-throughput cell analysis in fields such a...Imaging flow cytometry(IFC)combines the imaging capabilities of microscopy with the high throughput of flow cytometry,offering a promising solution for high-precision and high-throughput cell analysis in fields such as biomedicine,green energy,and environmental monitoring.However,due to limitations in imaging framerate and realtime data processing,the real-time throughput of existing IFC systems has been restricted to approximately 1000-10,000 events per second(eps),which is insufficient for large-scale cell analysis.In this work,we demonstrate IFC with real-time throughput exceeding 1,000,000 eps by integrating optical time-stretch(OTS)imaging,microfluidic-based cell manipulation,and online image processing.Cells flowing at speeds up to 15 m/s are clearly imaged with a spatial resolution of 780 nm,and images of each individual cell are captured,stored,and analyzed.The capabilities and performance of our system are validated through the identification of malignancies in clinical colorectal samples.This work sets a new record for throughput in imaging flow cytometry,and we believe it has the potential to revolutionize cell analysis by enabling highly efficient,accurate,and intelligent measurement.展开更多
Stress granules are non-membranous cytoplasmic foci induced by various stress conditions.It is a protective strategy used by cells to suppress overall translation during stress.In cancer cells,it was thought that the ...Stress granules are non-membranous cytoplasmic foci induced by various stress conditions.It is a protective strategy used by cells to suppress overall translation during stress.In cancer cells,it was thought that the formation of stress granules could protect them from apoptosis and induces resistance towards anti-cancer drugs or radiation treatment which makes the stress granules a potential target for cancer treatment.However,most of our understanding of stress granules are still in the stage of molecular and cell biology,and a transitional gap for its actual effect on clinical settings remains.In this review,we summarize the mechanism and effect of stress granules formation in cancer and try to illuminate its potential applications in cancer therapy,using breast cancer as an example.展开更多
基金supported by“Hygiene and Health Development Scientific Research Fostering Plan of Haidian District Beijing”(No.HP2021-31-50302).
文摘Objective:To explore the application of genetic abnormalities in the diagnosis of angioimmunoblastic T-cell lymphoma(AITL)and the reliable pathological prognostic factors.Methods:This study included 53 AITL cases,which were reviewed for morphological patterns,immunophenotypes,presence of Hodgkin and Reed-Sternberg(HRS)-like cells,and co-occurrence of B cell proliferation.The Epstein-Barr virus(EBV)-positive cells in tissues were counted,and cases were classified into“EBV encoded RNA(EBER)high-density”group if>50/HPF.Targeted exome sequencing was performed.Results:Mutation data can assist AITL diagnosis:1)with considerable HRS-like cells(20 cases):RHOA mutated in 14 cases(IDH2 co-mutated in 3 cases,4 cases with rare RHOA mutation),TET2 was mutated in 5 cases(1 case comutated with DNMT3A),and DNMT3A mutated in 1 case;2)accompanied with B cell lymphoma(7 cases):RHOA mutated in 4 cases(1 case had IDH2 mutation),TET2 mutated in 2 cases and DNMT3A mutated in 1 case;3)mimic peripheral T cell lymphoma,not otherwise specified(5 cases):RHOA mutated in 2 cases(IDH2 co-mutated in 1 case),TET2 mutated in 3 cases,and DNMT3A mutated in 1 case;4)pattern 1(1 case),RHOA and TET2 co-mutated.Besides RHOAG17V(30/35),rare variant included RHOAK18N,RHOAR68H,RHOAC83Y,RHOAD120G and RHOAG17del,IDH2R172 co-mutated with IDH2M397V in one case.There were recurrent mutations of FAT3,PCLO and PIEZO1 and genes of epigenetic remodeling,T-cell activation,APC and PI3K/AKT pathway.EBER high-density independently indicated adverse overall survival and progression-free survival(P=0.046 and P=0.008,KaplanMeier/log-rank).Conclusions:Over half AITL cases might be confused in diagnosis for certain conditions without mutation data.Targeted exome sequencing with a comprehensive panel is crucial to detect both hot-spot and rare mutation variants for RHOA and IDH2 and other recurrent mutated genes in addition to TET2 and DNMT3A.EBER highdensity independently indicated adverse survival.
基金supported by the National Key R&D Program of China(2023YFF0723300)National Natural Science Foundation of China(62475198,62075200,12374295)+8 种基金Fundamental Research Funds for the Central Universities(2042024kf0003,2042024kf1010,2042023kf0105)Hubei Provincial Natural Science Foundation of China(2023AFB133)Jiangsu Science and Technology Program(BK20221257)Shenzhen Science and Technology Program(JCYJ20220530140601003,JCYJ20230807090207014)Translational Medicine and Multidisciplinary Research Project of Zhongnan Hospital of Wuhan University(ZNJC202217,ZNJC202232)The Interdisciplinary Innovative Talents Foundation from Renmin Hospital of Wuhan University(JCRCYR-2022-006)Hubei Province Young Science and Technology Talent Morning Hight Lift Project(202319)The Fund of National Key Laboratory of Plasma Physics(6142A04230201)We gratefully acknowledge Serendipity Lab for facilitating collaboration opportunities.
文摘Imaging flow cytometry(IFC)combines the imaging capabilities of microscopy with the high throughput of flow cytometry,offering a promising solution for high-precision and high-throughput cell analysis in fields such as biomedicine,green energy,and environmental monitoring.However,due to limitations in imaging framerate and realtime data processing,the real-time throughput of existing IFC systems has been restricted to approximately 1000-10,000 events per second(eps),which is insufficient for large-scale cell analysis.In this work,we demonstrate IFC with real-time throughput exceeding 1,000,000 eps by integrating optical time-stretch(OTS)imaging,microfluidic-based cell manipulation,and online image processing.Cells flowing at speeds up to 15 m/s are clearly imaged with a spatial resolution of 780 nm,and images of each individual cell are captured,stored,and analyzed.The capabilities and performance of our system are validated through the identification of malignancies in clinical colorectal samples.This work sets a new record for throughput in imaging flow cytometry,and we believe it has the potential to revolutionize cell analysis by enabling highly efficient,accurate,and intelligent measurement.
基金This work was supported by the National Natural Science Foundation of China(No.82002979 and 81702839)the Scientific Research and Development Funds of Peking Uni・versity People's Hospital,China(No.RDY2020-16).
文摘Stress granules are non-membranous cytoplasmic foci induced by various stress conditions.It is a protective strategy used by cells to suppress overall translation during stress.In cancer cells,it was thought that the formation of stress granules could protect them from apoptosis and induces resistance towards anti-cancer drugs or radiation treatment which makes the stress granules a potential target for cancer treatment.However,most of our understanding of stress granules are still in the stage of molecular and cell biology,and a transitional gap for its actual effect on clinical settings remains.In this review,we summarize the mechanism and effect of stress granules formation in cancer and try to illuminate its potential applications in cancer therapy,using breast cancer as an example.
