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Circ_0012152 Accelerates acute myeloid leukemia Progression through the miR-652-3p/SOX4 Axis

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Current Medical Science 2024年第3期44卷 611-622页

作者： Ying CHEN Bi-xia LI Ting-ting NIU Shu-jun YANG Li-chao WU Le-huai SHI Duo-bing ZOU Ning-ning WU Li-xia SHENG Xiao YAN Gui-fang OUYANG Qi-tian MU Laboratory of Stem Cell Transplantation The First Affiliated Hospital of Ningbo UniversityNingbo315300China Ningbo Clinical Research Center For Hematologic Malignancies Ningbo315300China Department of Hematology The First Affiliated Hospital of Ningbo UniversityNingbo315300China School of Medicine Hangzhou City UniversityZhejiang UniversityHangzhou310000China Key Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang Province Ningbo315300China

Objective acute myeloid leukemia(AML)is an aggressive hematological malignancy characterized by abnormal myeloid blast *** studies have demonstrated that circular RNAs play a role in AML *** this study,we aimed to investigate the clinical significance of circ_0012152 in AML and elucidate its underlying molecular mechanism in the pathogenesis of this *** Circ_0012152 expression was detected by quantitative real-time polymerase chain reaction in samples obtained from 247 patients with AML and 40 healthy controls.A systematic analysis of clinical characteristics and prognostic factors was also *** growth was assessed using the Cell Counting Kit-8(CCK-8)assay,and apoptosis and cell cycle progression were evaluated by flow ***,RNA pull-down was performed to identify target microRNAs,and transcriptome RNA sequencing and bioinformatics analyses were utilized to identify downstream mRNA *** Circ_0012152 was significantly upregulated in samples from patients with AML and served as an independent adverse prognostic factor for overall survival(OS)(hazard ratio:2.357;95%confidence interval 1.258–4.415).The circ_0012152 knockdown reduced cell growth,increased apoptosis,and inhibited cell cycle progression in AML cell *** pull-down and sequencing identified miR-652-3p as a target microRNA of circ_*** growth inhibition by circ_0012152 knockdown was significantly relieved by miR-652-3p *** suggested that miR-652-3p targeted SOX4,as the decrease in SOX4 expression resulting from circ_0012152 knockdown was upregulated by miR-652-3p inhibitors in AML *** Circ_0012152 is an independent poor prognostic factor for OS in AML,and it promotes AML cell growth by upregulating SOX4 through miR-652-3p.

关键词： acute myeloid leukemia circ_0012152 miR-652-3p SOX4 cell growth

Pediatric acute myeloid leukemia patients with i(17)(q10)mimicking acute promyelocytic leukemia:Two case reports

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World Journal of Clinical Cases 2022年第16期10卷 5446-5455页

作者： Hong-Xia Yan Wei-Hua Zhang Jin-Quan Wen Yan-He Liu Bao-Juan Zhang A-Duo Ji Department of Healthcare Rainbow Hospital of XianyangXianyang 721000Shaanxi ProvinceChina Department of Pediatric Intensive Care Unit Rainbow Hospital of XianyangXianyang 721000Shaanxi ProvinceChina Department of Pediatric Hematology/Oncology Rainbow Hospital of XianyangXianyang 721000Shaanxi ProvinceChina Department of Pediatric Hemato-logy/Oncology Rainbow Hospital of XianyangXianyang 721000Shaanxi ProvinceChina

BACKGROUND Chromosome i(17)(q10)abnormality is mainly associated with chronic myeloid leukemia(CML),myelodysplastic syndrome/myeloproliferative tumors(MDS/MPD),and acute myeloid leukemia(AML).The role of i(17)(q10)in AML is still unknown,the differences between AML and acute promyelocytic leukemia(APL)-like AML with i(17)(q10)need more *** study aimed to investigate the clinical characteristics and laboratory evidence of 2 AML cases with i(17)(q10),similar to APL *** SUMMARY Both pediatric patients were males;case 1 had newly diagnosed AML,and case 2 showed relapsed tumor after 1 year of drug *** marrow cell morphology,chromosome karyotype analysis,Fully-instrumented submersible housing test,immunological assays,molecular biological methods,and blood tumor panoramic gene test were ***-trans retinoic acid(ATRA)combined with arsenic acid(As2O3)were used in the first course of *** marrow was dominated by abnormal promyelocytic *** test revealed i(17)(q10)*** phenotype mainly included positive expressions of CD9,CD13,CD33,and *** 1 suffered intracranial hemorrhage after re-chemotherapy and died on *** case 2,on D145 and D265,bone marrow promyelocytic granulocytes accounted for 2%.Flow cytometric residual lesion detection showed no abnormal immunophenotype *** copy number of WT1 gene in two cases were 1087 and 1010,respectively,and the expression rates were 55.29% and 59.5%,*** ATRA,As2O3,and chemotherapy may be ineffective in treating APL-like AML with i(17)(q10)but without t(15;17)and PML-RARA fusion gene.

关键词： Chromosome i(17)(q10) Gene mutations acute promyelocytic leukemia acute myeloid leukemia Case report

Elevated nuclear phospho-eIF4E body levels are associated with tumor progression and poor prognosis for acute myeloid leukemia

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BIOCELL 2021年第3期45卷 711-722页

作者： HONG ZHOU XIAOFENG JIA FAN YANG Department of Hematology Affiliated Hangzhou First People’s HospitalZhejiang University School of MedicineHangzhou310006China College of Life Sciences China Jiliang UniversityHangzhou310018China

Uncontrolled proliferation is a hallmark of cancer cells,yet the molecular mechanisms that contribute to this proliferation are *** treatment of cancer is suboptimal in many cases,with no accurate index by which to evaluate the success of treatment or patient *** this study,we explored the protein levels of nuclear phospho-eIF4E in acute myeloid leukemia(AML)cell lines and primary leukemia samples by Western blot and immunofluorescence and as well analyzed transcriptomes by *** found nuclear phospho-eIF4E,an exporter of oncogenic mRNAs,to be abundant in ***,nuclear phospho-eIF4E abundance was significantly associated with tumor burden as well as the response of AML patients to *** results demonstrate“massive clustering and export of oncogenic mRNAs to the translation machinery”by highly abundant RNA-nuclear phospho-eIF4E *** is an efficient mechanism that may drive the proliferation of cancer ***,nuclear phospho-eIF4E bodies were identified as potential markers of AML,which may be useful for prognosis and as targets for cancer therapy.

关键词： acute myeloid leukemia Nuclear phospho-eIF4E Poor prognosis

A model based on eight iron metabolism-related genes accurately predicts acute myeloid leukemia prognosis

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BIOCELL 2023年第3期47卷 593-605页

作者： ZHANSHU LIU XI HUANG Department of Hematology Yongchuan Hospital of Chongqing Medical UniversityChongqing402160China Department of Hematology The Second Affiliated Hospital of Chongqing Medical UniversityChongqing400010China

Purpose:Iron metabolism maintains the balance between iron absorption and *** iron metabolism can cause numerous diseases,including *** study determined the iron metabolism-related genes(IMRGs)signature that can predict the prognosis of acute myeloid leukemia(AML).The roles of these genes in the immune microenvironment were also ***:A total of 514 IMRGs were downloaded from the Molecular Characteristics Database(MSigDB).IMRGs related to AML prognosis were identified using Cox regression and LASSO analyses and were used to construct the risk score *** patients were stratified into high-risk groups(cluster 1)and low-risk groups(cluster 2)based on the mean value of the risk *** accuracy and prognosis prediction potential of the risk-score model was evaluated using Kaplan-Meier and receiver operating characteristics *** stromal score,immune scores,and immune cells infiltrated in AML samples were estimated using CIBERSORT,MCPcountre,and Xcell *** role of immune checkpoint genes in the AML microenvironment and the prognostic value of the IMRGs were also ***:An AML prognosis prediction model was established based on the eight most critical *** analyses revealed that the model could accurately predict AML *** expression of IMRGs correlated with the infiltration of several immune cells and could influence response to certain chemotherapy drugs and ***:A model based on IMRGs can accurately predict the overall survival and disease-free survival of AML patients.

关键词： acute myeloid leukemia IMRGs Prognostic signature Infiltrating immune cells Bioinformatics

Secondary peripheral T-cell lymphoma and acute myeloid leukemia after Burkitt lymphoma treatment:A case report

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World Journal of Clinical Cases 2021年第24期9卷 7237-7244页

作者： Li Huang Can Meng Dan Liu Xiang-Jun Fu Department of Hematology Hainan General HospitalHainan Affiliated Hospital of Hainan Medical UniversityHaikou 570311Hainan ProvinceChina

BACKGROUND Multiple primary cancer refers to more than one synchronous or sequential cancer in the same *** primary cancer always presents as solid cancer or acute myeloid leukemia(AML)secondary to ***,we report a rare case of secondary peripheral T-cell lymphoma and AML after Burkitt lymphoma *** SUMMARY A 54-year-old female patient was admitted to our hospital complaining of edema on her left lower *** examination revealed multiple superficial lymphadenectasis on her neck and *** ultrasonography examination showed multiple uterine fibroids and a solid mass at the lower left side of the *** biopsy revealed Burkitt *** three hyper-CVAD(A+B)regimens,she achieved complete *** years later,lymphadenectasis reoccurred.A relevant biopsy confirmed the diagnosis of peripheral T-cell lymphoma,which was accompanied by gastrointestinal invasion and ***,bone marrow examination revealed *** the second day of scheduled treatment,she developed gastrointestinal bleeding,peptic ulcers,and hemorrhagic shock and was critically *** was then discharged from the hospital due to financial *** This is the first report of secondary peripheral T-cell lymphoma and AML after Burkitt lymphoma treatment with heterochronous and synchronal multiple primary cancers.

关键词： Burkitt lymphoma Peripheral T-cell lymphoma acute myeloid leukemia Multiplicity carcinoma Positron emission tomography-computed tomography Case report

Comparison of Mitoxantrone in Combination with Intermediate-dose Cytarabine versus High-dose Cytarabine as Consolidation Therapies for Young Non-APL acute myeloid leukemia Patients with Favorable and Intermediate Cytogenetics

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2018年第1期38卷 51-57页

作者： Ji-hao ZHOU Hai-qing LIN Qi SHEN Li-na HU Guo-qiang LI Xiong-fei SUN Xin-you ZHANG Department of Hematology The Second Clinical Medical College of Jinan University （Shenzhen People＇s Hospital） Jinan University Shenzhen 518020 China

In this study,we compared the efficacy of mitoxantrone in combination with intermediate-dose cytarabine（HAM） with that of high-dose cytarabine alone（Hi DAC） as consolidation regimens in non-acute promyelocytic leukemia（APL） acute myeloid leukemia patients with favorable and intermediate cytogenetics.A total of 62 patients from Shenzhen People＇s Hospital were enrolled in this *** patients enrolled received standard induction chemotherapy and achieved the first complete remission（CR1）.In these patients,24 received Hi DAC and 38 received HAM as *** median relapse free survival（RFS） and overall survival（OS） were similar between these two consolidation *** in subgroup analysis according to risk stratification,the combination regimen conferred no benefit in longterm outcome in patients with favorable or intermediate ***,in patients receiving HAM regimen,the lowest neutrophil count was lower,neutropenic period longer,neutropenic fever rate higher,and more platelet transfusion support was *** group also tended to have higher rate of sepsis than Hi DAC *** to our results,we suggest that combination treatment with mitoxantrone and intermediate-dose cytarabine has limited value as compared to Hi DAC,even in young non-APL AML patients with favorable and intermediate cytogenetics.

关键词： cytarabine mitoxantrone consolidation acute myeloid leukemia cytogenetics

Genetic changes in refractory relapsed acute myeloid leukemia with NPM1 mutation:A case report

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World Journal of Clinical Cases 2022年第35期10卷 13058-13063页

作者： Shuang-Ling Wang Department of Hematology and Oncology The Second Affiliated Hospital of Medical College of Shantou UniversityShantou 515041Guangdong ProvinceChina

BACKGROUND acute myeloid leukemia is often associated with gene mutation or chromosome abnormality,which is an important factor affecting *** 5-year survival rate of patients with acute myeloid leukemia without hematopoietic stem cell transplantation is *** patients who only received chemotherapy and whose first remission lasted>5 years,there are few reports of gene spectrum changes between relapse and initial *** SUMMARY We report a 41-year-old woman who presented to our hospital with complaints of dizziness,poor appetite and *** was diagnosed with acute myelomonocytic leukemia(M4b)with NPM1 mutation and only received *** first remission lasted>5 *** genetic variants were detected upon relapse that may have been related to relapse and chemotherapy *** Mutations in WT1(R394fs/A387fs)/PTPN11 T73I/ETV6 S350P and JAK2 W659R may be related to relapse and chemotherapy resistance in acute myeloid leukemia.

关键词： acute myeloid leukemia NPM1 mutation Genetic variants WT1 Case report

High-performance SOD mimetic enzyme Au@Ce for arresting cell cycle and proliferation of acute myeloid leukemia

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Bioactive Materials 2022年第4期7卷 117-130页

作者： Yuxiang Sun Xin Liu Lei Wang Li Xu Kunliang Liu Lei Xu Fangfang Shi Yu Zhang Ning Gu Fei Xiong State Key Laboratory of Bioelectronics Jiangsu Key Laboratory for Biomaterials and DevicesSchool of Biological Science and Medical Engineering&Collaborative Innovation Center of Suzhou Nano-Science and TechnologySoutheast UniversityNanjing210096PR China Department of Gastroenterology Nanjing Drum Tower HospitalAffiliated Hospital of Nanjing University Medical SchoolNanjing UniversityNanjingPR China Jiangsu Key Laboratory of Molecular Medicine Medical School of Nanjing UniversityNanjing210093PR China Department of Research and Development Jinan Guoke Medical Technology Development Co.Ltd.Address:No.1Gangxing 3rd RoadHigh-tech Industrial Development ZoneJinan CityShandong Province250013PR China Department of Oncology Zhongda HospitalSoutheast UniversityNanjing 210009China

SOD-like activity of CeO_(2) nanoparticles(Ce NPs)is driven by Ce^(3+)/Ce^(4+),high oxidative stress can oxidize Ce^(3+) to reduce the ratio of Ce^(3+)/Ce^(4+),inactivating the SOD activity of Ce ***,we found Au@Ce NPs,assembled by Au NPs and Ce NPs,exhibited high-performance of SOD mimetic enzyme activity even upon the oxidation of H_(2)O_(2).Ce NPs supported by nano-Au can acquire the electrons from Au NPs through the enhanced localized surface plasmon resonance(LSPR),maintaining the stability of Ce^(3+)/Ce^(4+) and SOD-like ***,Au@Ce NPs retained the peroxidase function and catalase *** a result,Au@Ce NPs effectively scavenged O_(2·-) and the derived ROS in AML cells,which are the important signaling source that drives AML cell proliferation and accelerates cell cycle *** HL-60 cells were treated by Au@Ce NPs,the removal of endogenous ROS signal significantly arrested cell cycle at G1 phase and suppressed the cell proliferation by blocking the mitogen-activated protein kinases(MAPKs)signaling and the Akt/Cyclin D1 cell cycle ***,this treatment strategy showed therapeutic effect for subcutaneous transplantation of AML model as well as a satisfactory result in diminishing the leukocyte infiltration of liver and spleen ***,assembled Au@Ce NPs show the high-performance SOD-like activity,promising the potential in treating AML and regulating abnormal ROS in other diseases safely and efficiently.

关键词： Superoxide dismutase Au nanoparticles CeO_(2)nanoparticles Reactive oxygen species acute myeloid leukemia

High frequency of CD34+CD38-/low immature leukemia cells is correlated with unfavorable prognosis in acute myeloid leukemia

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World Journal of Stem Cells 2017年第12期9卷 227-234页

作者： Adriana Plesa Charles Dumontet Eve Mattei Ines Tagoug Sandrine Hayette Pierre Sujobert Isabelle Tigaud Marie Pierre Pages Youcef Chelghoum Fiorenza Baracco Helene Labussierre Sophie Ducastelle Etienne Paubelle Franck Emmanuel Nicolini Mohamed Elhamri Lydia Campos Claudiu Plesa Stéphane Morisset Gilles Salles Yves Bertrand Mauricette Michallet Xavier Thomas Laboratory of Hematology Lyon-Sud HospitalHospices Civils de Lyon CRCL INSERM 1052/CNRS 5286 Department of Hematology Hospices Civils de Lyon Laboratory of Hematology Nord Hospital Statistical and Clinical Research Lyon-Sud HospitalHospices Civils de Lyon Department of Pediatric Hematology and BMT IHOP Lyon

AIM To evaluate the importance of the CD34+CD38-cell population when compared to the CD34+CD38+/low and CD34+CD38+/high leukemic cell sub-populations and to determine its correlations with leukemia characteristics and known prognostic factors, as well as with response to therapy and *** Two hundred bone marrow samples were obtained at diagnosis from 200 consecutive patients with newly diagnosed acute myeloid leukemia(AML) were studied between September 2008 and December 2010 at our Institution(Hematology Department, Lyon, France). The CD34/CD38 cell profile was analyzed by multiparameter flowcytometry approach using 8 C panels and FACS CANTO and Diva software(BD Bioscience).RESULTS We analyzed CD34 and CD38 expression in bone marrow samples of 200 AML patients at diagnosis, and investigated the prognostic value of the most immature CD34+CD38-population. Using a cut-off value of 1% of CD34+CD38-from total "bulk leukemic cells" we found that a high(> 1%) level of CD34+CD38-blasts at diagnosis was correlated with advanced age, adverse cytogenetics as well as with a lower rate of complete response after induction and shorter disease-free survival. In a multivariate analysis considering age, leukocytosis, the % of CD34+ blasts cells and the standardized cytogenetic and molecular risk subgroups, a percentage of CD34+CD38-leukemic cells > 1% was an independent predictor of DFS [HR = 2.8(1.02-7.73), P = 0.04] and OS [HR = 2.65(1.09-6.43), P = 0.03].CONCLUSION Taken together, these results show that a CD34/CD38 "backbone" for leukemic cell analysis by multicolour flowcytometry at diagnosis provides useful prognostic information.

关键词： CD34+CD38-/low Immunophenotyping Leukemic stem cells acute myeloid leukemia Prognosis