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Novel PIKfyve/Tubulin Dual-target Inhibitor as a Promising Therapeutic Strategy for B-cell Acute Lymphoblastic Leukemia
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作者 Zhen LU Qian LAI +8 位作者 Zhi-feng LI Meng-ya ZHONG Yue-long JIANG Li-ying FENG Jie ZHA Jing-wei YAO Yin LI Xian-ming DENG Bing XU 《Current Medical Science》 SCIE CAS 2024年第2期298-308,共11页
Objective:In B-cell acute lymphoblastic leukemia(B-ALL),current intensive chemotherapies for adult patients fail to achieve durable responses in more than 50%of cases,underscoring the urgent need for new therapeutic r... Objective:In B-cell acute lymphoblastic leukemia(B-ALL),current intensive chemotherapies for adult patients fail to achieve durable responses in more than 50%of cases,underscoring the urgent need for new therapeutic regimens for this patient population.The present study aimed to determine whether HZX-02-059,a novel dual-target inhibitor targeting both phosphatidylinositol-3-phosphate 5-kinase(PIKfyve)and tubulin,is lethal to B-ALL cells and is a potential therapeutic for B-ALL patients.Methods:Cell proliferation,vacuolization,apoptosis,cell cycle,and in-vivo tumor growth were evaluated.In addition,Genome-wide RNA-sequencing studies were conducted to elucidate the mechanisms of action underlying the anti-leukemia activity of HZX-02-059 in B-ALL.Results:HZX-02-059 was found to inhibit cell proliferation,induce vacuolization,promote apoptosis,block the cell cycle,and reduce in-vivo tumor growth.Downregulation of the p53 pathway and suppression of the phosphoinositide 3-kinase(PI3K)/AKT pathway and the downstream transcription factors c-Myc and NF-κB were responsible for these observations.Conclusion:Overall,these findings suggest that HZX-02-059 is a promising agent for the treatment of B-ALL patients resistant to conventional therapies. 展开更多
关键词 b-cell acute lymphoblastic leukemia dual-target inhibitor NF-KB c-Myc PI3K/AKT p53
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Coexistence of diffuse large B-cell lymphoma,acute myeloid leukemia,and untreated lymphoplasmacytic lymphoma/waldenström macroglobulinemia in a same patient:A case report
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作者 Liu-Bo Zhang Lu Zhang +8 位作者 Hong-Lei Xin Yan Wang Hong-Yu Bao Qing-Qi Meng Su-Yu Jiang Xue Han Wan-Ru Chen Jian-Ning Wang Xiao-Feng Shi 《World Journal of Clinical Cases》 SCIE 2023年第18期4295-4305,共11页
BACKGROUND The Coexistence of myeloid and lymphoid malignancies is rare.Myeloid leukemia occurs more frequently as a secondary event in patients receiving chemotherapy agents for lymphoid malignancies.Synchronous diag... BACKGROUND The Coexistence of myeloid and lymphoid malignancies is rare.Myeloid leukemia occurs more frequently as a secondary event in patients receiving chemotherapy agents for lymphoid malignancies.Synchronous diagnoses of diffuse large B-cell lymphoma(DLBCL),acute myeloid leukemia(AML),and untreated lymphoplasmacytic lymphoma/Waldenström macroglobulinemia(LPL/WM)in the same patient have not been reported.Here we report one such case.CASE SUMMARY An 89-year-old man had a chest wall mass histopathologically diagnosed as DLBCL.The bone marrow and peripheral blood contained two groups of cells.One group of cells fulfilled the criteria of AML,and the other revealed the features of small B lymphocytic proliferative disorder,which we considered LPL/WM.Multiple chromosomal or genetic changes were detected in bone marrow mononuclear cells,including ATM deletion,CCND1 amplification,mutations of MYD88(L265P)and TP53,WT1 overexpression,and fusion gene of BIRC2-ARAP1,as well as complex chromosomal abnormalities.The patient refused chemotherapy because of old age and died of pneumonia 1 mo after the final diagnosis.CONCLUSION The coexistence of DLBCL,AML,and untreated LPL/WM in the same patient is extremely rare,which probably results from multiple steps of genetic abnormalities.Asymptomatic LPL/WM might have occurred first,then myelodysplastic syndromerelated AML developed,and finally aggressive DLBCL arose.Therefore,medical staff should pay attention to this rare phenomenon to avoid misdiagnoses. 展开更多
关键词 Diffuse large b-cell lymphoma Acute myeloid leukemia Small B lymphocyte proliferative disorder Lymphoplasmacytic lymphoma/Waldenström macroglobulinemia COEXISTENCE Case report
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Individualized leukemia cell-population profiles in common B-cell acute lymphoblastic leukemia patients 被引量:3
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作者 Jian-Hua Yu Jing-Tao Dong +5 位作者 Yong-Qian Jia Neng-Gang Jiang Ting-Ting Zeng Hong Xu Xian-Ming Mo Wen-Tong Meng 《Chinese Journal of Cancer》 SCIE CAS CSCD 2013年第4期213-223,共11页
Immunophenotype is critical for diagnosing common B-cell acute lymphoblastic leukemia (common ALL) and detecting minimal residual disease. We developed a protocol to explore the immunophenotypic profiles of common ALL... Immunophenotype is critical for diagnosing common B-cell acute lymphoblastic leukemia (common ALL) and detecting minimal residual disease. We developed a protocol to explore the immunophenotypic profiles of common ALL based on the expression levels of the antigens associated with B lymphoid development, including IL-7Rα (CD127), cytoplasmic CD79a (cCD79a), CD19, VpreB (CD179a), and sIgM, which are successive and essential for progression of B cells along their developmental pathway. Analysis of the immunophenotypes of 48 common ALL cases showed that the immunophenotypic patterns were highly heterogeneous, with the leukemic cell population differing from case to case. Through the comprehensive analysis of immunophenotypic patterns, the profiles of patient-specific composite leukemia cell populations could provide detailed information helpful for the diagnosis, therapeutic monitoring, and individualized therapies for common ALL. 展开更多
关键词 COMMON b-cell acute LYMPHOBLASTIC leukemia immunophenotype diagnosis heterogeneity flow CYTOMETRY
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SYK as a New Therapeutic Target in B-Cell Precursor Acute Lymphoblastic Leukemia 被引量:1
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作者 Fatih M. Uckun Sanjive Qazi 《Journal of Cancer Therapy》 2014年第1期124-131,共8页
The identification of SYK as a master regulator of apoptosis controlling the activation of the PI3-K/AKT, NFκB, and STAT3 pathways—three major anti-apoptotic signaling pathways in B-lineage leukemia/lymphoma cells—... The identification of SYK as a master regulator of apoptosis controlling the activation of the PI3-K/AKT, NFκB, and STAT3 pathways—three major anti-apoptotic signaling pathways in B-lineage leukemia/lymphoma cells—prompts the hypothesis that rationally designed inhibitors targeting SYK may overcome the resistance of malignant B-lineage lymphoid cells to apoptosis and thereby provide the foundation for more effective multi-modality treatment regimens for poor prognosis B-precursor acute lymphoblastic leukemia (BPL). In recent preclinical proof-of-concept studies, a liposomal nanoparticle (LNP) formulation of a SYK substrate-binding site inhibitor, known as C61, has been developed as a nanomedicine candidate against poor prognosis and relapsed BPL. This nanoscale formulation of C61 exhibited a uniquely favorable pharmacokinetics and safety profile in mice, induced apoptosis in radiation-resistant primary leukemic cells taken directly from BPL patients as well as in vivo clonogenic BPL xenograft cells, destroyed the leukemic stem cell fraction of BPL blasts, and exhibited potent in vivo anti-leukemic activity in xenograft models of aggressive BPL. Further development of C61-LNP may provide the foundation for new and effective treatment strategies against therapy-refractory BPL. 展开更多
关键词 STAT3 SYK KINASE PHOSPHORYLATION Apoptosis leukemia NANOMEDICINE
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Prognostic Significance of Apoptosis Regulators in B-Cell Chronic Lymphocytic Leukemia
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作者 Ahmad Baraka Shereen El Shorbagy +4 位作者 Ola M. Elfarargy Rasha Haggag Lobna A. Abdelaziz Salah F. Elsayed Khaled A. Elbana 《Journal of Cancer Therapy》 2017年第4期360-385,共26页
Background: High levels of MCL-1 and BCL-2 proteins have been found in Chronic Lymphocytic Leukemia (CLL), and inversely correlated with response to treatment. BCL-2/Bax ratio is the main director of apoptosis in CLL.... Background: High levels of MCL-1 and BCL-2 proteins have been found in Chronic Lymphocytic Leukemia (CLL), and inversely correlated with response to treatment. BCL-2/Bax ratio is the main director of apoptosis in CLL. The study aimed to clarify the prognostic role of MCL-1, BCL-2 and BCL-2/ Bax ratio in B-CLL. Patients & method: Estimation of MCL-1, BCL-2 and Bax expressions by a flow cytometry in 45 B-CLL patients and the prognostic value of these markers were correlated with other well-known established prognostic markers and treatment response. Results: MCL-1 was expressed in 60% of cases while BCL-2 was expressed in 82.2% of cases. MCL-1 expression was significantly high in male gender, short lymphocyte doubling time (LDT), and high expression of CD 38 (p β2M, CD38 expression), low ZAP-70 expression, splenomegaly and higher Rai stage were significantly increased in patients with high expression of BCL-2 (p β2M, high C-D38 expression, low ZAP-70 expression, the poor cytogenetic and splenomegaly in patients with high expression of BCL-2/ Bax ratio (p In conclusion: MCL-1, BCL-2 expressions and BCL-2/Bax ratio could be useful potential predictive and prognostic markers in B-CLL. 展开更多
关键词 MYELOID Cell leukemia 1 b-cell LYMPHOMA 2 BAX b-cell Chronic LYMPHOCYTIC leukemia
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Diphtheria Toxin/Human B-Cell Activating Factor Fusion Protein Kills Human Acute Lymphoblastic Leukemia BALL-1 Cells: An Experimental Study
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作者 Xin-pu Gao Zheng-min Liu +5 位作者 Yu-lian Jiao Bin Cui Yue-ting Zhu Jie Zhang Lai-cheng Wang Yue-ran Zhao 《Chinese Journal of Cancer Research》 SCIE CAS CSCD 2012年第3期238-244,共7页
Objective: This study aimed to express a fusion protein of diphtheria toxin and human B cell-activating factor (DT388sBAFF) in Escherichia coli (E. coli) and investigate its activity in human B-lineage acute lymp... Objective: This study aimed to express a fusion protein of diphtheria toxin and human B cell-activating factor (DT388sBAFF) in Escherichia coli (E. coli) and investigate its activity in human B-lineage acute lymphoblastic leukemia 1 cells (BALL-1). Methods: A fragment of DT388sBAFF fusion gene was separated from plasmid pUC57-DT388sBAFF digested with Nde I and Xho I, and inserted into the expression vector pcold II digested with the same enzymes. Recombinants were screened by the colony polymerase chain reaction (PCR) and restriction map. The recombinant expression vector was transformed into BL21 and its expression was induced by isopropyl β-D-1-thiogalactopyranoside (IPTG). The recombinant protein was identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot, and then purified by Ni2+-NTA affinity chromatography. The expression level of B cell-activating factor receptor (BAFF-R) on BALL-1 cells was assessed by real-time PCR. The receptor binding capacity of recombinant protein was determined by cell fluorescent assay. The specific cytotoxicity of recombinant protein on BALL-1 cells was detected by 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assay. Results: The expression level of recombinant protein was 50% of total bacterial proteins in E. coli, and the recombinant protein could bind to BAFF-R-positive BALL-1 cells and thereby produce a cytotoxic effect on the cells. Conclusion: The fusion protein expression vector DT388sBAFF was successfully constructed and the recombinant protein with selective cytotoxicity against BALL-1 cells was obtained, providing foundation for further study of the therapy of human B-lineage acute lymphoblastic leukemia. 展开更多
关键词 B cell-activating factor B-lineage acute lymphoblastic leukemia Diphtheria toxin Fusion protein
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Mutation Analysis of IgVH Gene in B-Cell Chronic Lymphocytic Leukemia
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作者 王峰 朱慧芬 +2 位作者 朱丽娟 殷波涛 沈关心 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2002年第3期177-179,182,共4页
Summary: The variable heavy chain region (VH) genes of 3 untreated patients with B cell chronic lymphocytic leukemia (B CLL) were cloned and analyzed. The VH family used was VH3 11, VH3 72 and VH3 33. More than 2... Summary: The variable heavy chain region (VH) genes of 3 untreated patients with B cell chronic lymphocytic leukemia (B CLL) were cloned and analyzed. The VH family used was VH3 11, VH3 72 and VH3 33. More than 2 % difference from the corresponding germline gene was detected in all the 3 obtained potential functional genes (average 16.7). Mutation pattern analysis indicated evidence of antigen selective pressure observed in 1 of 3 cases. Our findings suggested that the tumor cells originate from post GC cells. 展开更多
关键词 immunoglobulin variable region mutation analysis B cell chronic lymphocytic leukemia
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Expression pattern of BIM,BCL-6,and c-MYC in adult B-cell acute lymphoblastic leukemia
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作者 Chanli Zheng Lin Xu +2 位作者 Yanjun Xie Dongmei He Yangqiu Li 《Oncology and Translational Medicine》 2017年第4期151-155,共5页
Objective We aimed to evaluate the expression pattern of the genes BIM, BCL-6, and c-MYC in adult patients at initial diagnosis of B-cell acute lymphoblastic leukemia(B-ALL).Methods Relative m RNA levels of BIM, BCL-6... Objective We aimed to evaluate the expression pattern of the genes BIM, BCL-6, and c-MYC in adult patients at initial diagnosis of B-cell acute lymphoblastic leukemia(B-ALL).Methods Relative m RNA levels of BIM, BCL-6, and c-MYC in peripheral blood mononuclear cells(PBMCs) from B-ALL patients were determined by quantitative reverse-transcription polymerase chain reaction(q RT-PCR) using SYBR Green dye. PBMCs from healthy volunteers served as a control. GAPDH was used as a reference gene.Results Relative expression of BIM, BCL-6, and c-MYC m RNA in B-ALL patients was significantly lower than in healthy controls(P < 0.05). Furthermore, this result was observed for both newly diagnosed B-ALL patients and those incomplete remission(CR)(P < 0.05). There were no statistically significant differences in the expression levels of BIM, BCL-6, and c-MYC between these B-ALL patient groups(P > 0.05). Spearman's rank correlation analyses revealed the expression level of BIM to be positively correlated with that of BCL-6 in B-ALL patients.Conclusion Expression of the genes BIM, BCL-6, and c-MYC is decreased in adult B-ALL patients. Moreover, the expression pattern of these genes may be similar in such patients at initial diagnosis and following CR. The expression characteristics of BIM, BCL-6, and c-MYC may constitute useful markers for the diagnosis of adult B-ALL. 展开更多
关键词 BIM BCL-6 C-MYC B cell acute LYMPHOBLASTIC leukemia (ALL) quantitative REVERSETRANSCRIPTION polymerase chain reaction (qRT-PCR)
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Expression of the B-Cell Lymphoma/Leukemia 11A Gene in Malignant Hematological Cell Lines through Quantitative Reverse Transcription Polymerase Chain Reaction
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作者 Yang-jun GAO Don-g-mei HE +3 位作者 Shao-hua CHEN Xiao-juan YAN Xiao-mao HU Yang-qiu LP 《Clinical oncology and cancer researeh》 CAS CSCD 2011年第4期242-246,共5页
The B-cell lymphoma/leukemia 11A (BCL11A) gene is essential for normal lymphoid development and has been associated with hematological malignancies. In the current study, the relative expression level of BCL11A in m... The B-cell lymphoma/leukemia 11A (BCL11A) gene is essential for normal lymphoid development and has been associated with hematological malignancies. In the current study, the relative expression level of BCL11A in malignant hematological cell lines was evaluated through real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). METHODS The relative expression level of BCLllA mRNA in malignant hematological cell lines was determined through qRT- PCR using SYBR Green I dye. Glyceraldehyde-3-phosphate dehydro- genase was used as the reference gene to confirm the relative expression level of BCL11A gene mRNA. RESULTS The relative expression level of BCL11A mRNA in cell lines from B-cell malignancies was significantly higher compared with that from acute rnyeloid leukemia (P 〈 0.05). Different cell lines with malignant B-cells exhibited a wide range of BCL11A expressions ranging from 27.37 to 93.38. CONCLUSION The overexpression of BCL11A gene mRNA in malignant B-cells might play a role in B-cell lymphoma/leukemia. 展开更多
关键词 b-cell lymphoma/leukemia 11A (BCL11A) malignantb-cells real-time quantitative reverse transcription-polymerasechain reaction.
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Carrimycin in the treatment of acute promyelocytic leukemia combined with pulmonary tuberculosis: A case report
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作者 Fu-Yu Yang Lei Shao +1 位作者 Jie Su Zhen-Meng Zhang 《World Journal of Clinical Cases》 SCIE 2024年第3期623-629,共7页
BACKGROUND Pulmonary tuberculosis(PTB)is prevalent in immunocompromised populations,including patients with hematologic malignancies,human immunodeficiency virus infections,and chronic diseases.Effective treatment for... BACKGROUND Pulmonary tuberculosis(PTB)is prevalent in immunocompromised populations,including patients with hematologic malignancies,human immunodeficiency virus infections,and chronic diseases.Effective treatment for acute promyelocytic leukemia(APL)combined with PTB is lacking.These patients show an extremely poor prognosis.Therefore,studies should establish efficient treatment options to improve patient survival and prognosis.CASE SUMMARY A 60-year-old male with pain in the right side of his chest and a fever for 4 d visited the outpatient department of our hospital.Peripheral blood smear revealed 54%blasts.Following bone marrow examinations,variant APL with TNRC18-RARA fusion gene was diagnosed.Chest computed tomography scan showed bilateral pneumonitis with bilateral pleural effusions,partial atelectasis in the lower lobes of both lungs,and the bronchoalveolar lavage fluid gene X-Pert test was positive,indicative of PTB.Carrimycin,ethambutol(EMB),and isoniazid(INH)were administered since he could not receive chemotherapy as the WBC count decreased continuously.After one week of treatment with carrimycin,the patient recovered from fever and received chemotherapy.Chemotherapy was very effective and his white blood cells counts got back to normal.After being given five months with rifampin,EMB and INH and chemotherapy,the patient showed complete remission from pneumonia and APL.CONCLUSION We report a case of PTB treated successfully with carrimycin with APL that requires chemotherapy. 展开更多
关键词 Carrimycin Hematologic disease Acute myeloid leukemia Acute promyelocytic leukemia Pulmonary tuberculosis Case report
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Identification of cell surface markers for acute myeloid leukemia prognosis based on multi-model analysis 被引量:1
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作者 Jiaqi Tang Lin Luo +18 位作者 Bakwatanisa Bosco Ning Li Bin Huang Rongrong Wu Zihan Lin Ming Hong Wenjie Liu Lingxiang Wu Wei Wu Mengyan Zhu Quanzhong Liu Peng Xia Miao Yu Diru Yao Sali Lv Ruohan Zhang Wentao Liu Qianghu Wang Kening Li 《Journal of Biomedical Research》 CAS CSCD 2024年第4期397-412,共16页
Given the extremely high inter-patient heterogeneity of acute myeloid leukemia(AML),the identification of biomarkers for prognostic assessment and therapeutic guidance is critical.Cell surface markers(CSMs)have been s... Given the extremely high inter-patient heterogeneity of acute myeloid leukemia(AML),the identification of biomarkers for prognostic assessment and therapeutic guidance is critical.Cell surface markers(CSMs)have been shown to play an important role in AML leukemogenesis and progression.In the current study,we evaluated the prognostic potential of all human CSMs in 130 AML patients from The Cancer Genome Atlas(TCGA)based on differential gene expression analysis and univariable Cox proportional hazards regression analysis.By using multi-model analysis,including Adaptive LASSO regression,LASSO regression,and Elastic Net,we constructed a 9-CSMs prognostic model for risk stratification of the AML patients.The predictive value of the 9-CSMs risk score was further validated at the transcriptome and proteome levels.Multivariable Cox regression analysis showed that the risk score was an independent prognostic factor for the AML patients.The AML patients with high 9-CSMs risk scores had a shorter overall and event-free survival time than those with low scores.Notably,single-cell RNA-sequencing analysis indicated that patients with high 9-CSMs risk scores exhibited chemotherapy resistance.Furthermore,PI3K inhibitors were identified as potential treatments for these high-risk patients.In conclusion,we constructed a 9-CSMs prognostic model that served as an independent prognostic factor for the survival of AML patients and held the potential for guiding drug therapy. 展开更多
关键词 acute myeloid leukemia cell surface markers PROGNOSIS drug sensitivity multi-model analysis
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Overview of novel nanobiosensors for electrochemical and optical diagnosis of leukemia:Challenge and opportunity
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作者 Ulya Farahdina Tahta Amrillah +3 位作者 Mashuri Mashuri Vannajan Sanghiran Lee Agus Rubiyanto Nasori Nasori 《Journal of Innovative Optical Health Sciences》 SCIE EI CSCD 2024年第4期116-138,共23页
Leukemia is one of the ten types of cancer that causes the biggest death in the world.Compared to other types of cancer,leukemia has a low life expectancy,so an early diagnosis of the cancer is necessary.A new strateg... Leukemia is one of the ten types of cancer that causes the biggest death in the world.Compared to other types of cancer,leukemia has a low life expectancy,so an early diagnosis of the cancer is necessary.A new strategy has been developed to identify various leukemia biomarkers by making blood cancer biosensors,especially by developing nanomaterial applications so that they can improve the performance of the biosensor.Although many biosensors have been developed,the detection of leukemia by using nanomaterials with electrochemical and optical methods is still less carried out compare to other types of cancer biosensors.Even the acoustic and calorimetric testing methods for the detection of leukemia by utilizing nanomaterials have not yet been carried out.Most of the reviewed works reported the use of gold nanoparticles and electrochemical characterization methods for leukemia detection with the object of study being conventional cancer cells.In order to be used clinically by the community,future research must be carried out with a lot of patient blood objects,develop non-invasive leukemia detection,and be able to detect all types of blood cancer specifically with one biosensor.This can lead to a fast and accurate diagnosis thus allowing for early treatment and easy periodic condition monitoring for various types of leukemia based on its biomarker and future design controlable via internet of things(IoT)so that why would be monitoring real times. 展开更多
关键词 BIOSENSOR detection leukemia NANOMATERIAL IoT
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Bone marrow microRNA-34a is a good indicator for response to treatment in acute myeloid leukemia
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作者 MONA SA BDELLATEIF NAGLAA MHASSAN +1 位作者 MAHMOUD MKAMEL YOMNA MEL-MELIGUI 《Oncology Research》 SCIE 2024年第3期577-584,共8页
Background:microRNA 34a(miR 34a)had been reported to have a diagnostic role in acute myeloid leukemia(AML).However,its value in the bone marrow(BM)of AML patients,in addition to its role in response to therapy is stil... Background:microRNA 34a(miR 34a)had been reported to have a diagnostic role in acute myeloid leukemia(AML).However,its value in the bone marrow(BM)of AML patients,in addition to its role in response to therapy is still unclear.The current study was designed to assess the diagnostic,prognostic,and predictive significance of miR 34a in the BM of AML patients.Methods:The miR.34a was assed in BM aspirate of 82 AML patients in relation to 12 normal control subjects using qRT-PCR.The data were assessed for correlation with the relevant dinical critenia,response to therapy,disease-free survival(DFS),and overall survival(OS)rates.Results:miR.34a was significantly downregulated in AML patients[0.005(3.3×10^(-6)-1.32)],compared to the control subjects[0.108(3.2× 10^(-4)-1.64),p=0.021].The.median relative quantification(RQ)of miR-34a was 0.106(range;0-32.12).The specifaity,sensitivity,and area under the curve(AUC)for the diagnosis of AML were(58.3%,69.5%,0.707,respectively,p=0.021).patients with upregulated miR-34a showed decreased platelets count<34.5 × 10^(9)/L,and achieved early complete remission(CR,p=0.031,p=0.044,respectively).Similarly,patients who were refractory to therapy showed decreased miR 34a levels in comparison to those who achieved CR[0.002(0-0.01)and 0.12(0-32.12),respectively,p=0.002].Therefore,miR 34a could significantly identify patients with CR with a specificity of 75%and sensitivity of 100%at a cut-off of 0.014(AUC=0.927,p=0.005).There was no considerable association between miR-34a expression and survival rates of the induded AML patients.Condusion:miR-34a could be a beneficial diagnostic biomarker for AML patients.In addition,it serves as a good indicator for response to therapy,which could possibly identify patients who are refractory to treatment with 100%sensitivity and 75%specificity. 展开更多
关键词 AML miR 34a MICRORNA leukemia
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A New Method for Diagnosis of Leukemia Utilizing a Hybrid DL-ML Approach for Binary and Multi-Class Classification on a Limited-Sized Database
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作者 Nilkanth Mukund Deshpande Shilpa Gite +2 位作者 Biswajeet Pradhan Abdullah Alamri Chang-Wook Lee 《Computer Modeling in Engineering & Sciences》 SCIE EI 2024年第4期593-631,共39页
Infection of leukemia in humans causes many complications in its later stages.It impairs bone marrow’s ability to produce blood.Morphological diagnosis of human blood cells is a well-known and well-proven technique f... Infection of leukemia in humans causes many complications in its later stages.It impairs bone marrow’s ability to produce blood.Morphological diagnosis of human blood cells is a well-known and well-proven technique for diagnosis in this case.The binary classification is employed to distinguish between normal and leukemiainfected cells.In addition,various subtypes of leukemia require different treatments.These sub-classes must also be detected to obtain an accurate diagnosis of the type of leukemia.This entails using multi-class classification to determine the leukemia subtype.This is usually done using a microscopic examination of these blood cells.Due to the requirement of a trained pathologist,the decision process is critical,which leads to the development of an automated software framework for diagnosis.Researchers utilized state-of-the-art machine learning approaches,such as Support Vector Machine(SVM),Random Forest(RF),Na飗e Bayes,K-Nearest Neighbor(KNN),and others,to provide limited accuracies of classification.More advanced deep-learning methods are also utilized.Due to constrained dataset sizes,these approaches result in over-fitting,reducing their outstanding performances.This study introduces a deep learning-machine learning combined approach for leukemia diagnosis.It uses deep transfer learning frameworks to extract and classify features using state-of-the-artmachine learning classifiers.The transfer learning frameworks such as VGGNet,Xception,InceptionResV2,Densenet,and ResNet are employed as feature extractors.The extracted features are given to RF and XGBoost classifiers for the binary and multi-class classification of leukemia cells.For the experimentation,a very popular ALL-IDB dataset is used,approaching a maximum accuracy of 100%.A private real images dataset with three subclasses of leukemia images,including Acute Myloid Leukemia(AML),Chronic Lymphocytic Leukemia(CLL),and Chronic Myloid Leukemia(CML),is also employed to generalize the system.This dataset achieves an impressive multi-class classification accuracy of 97.08%.The proposed approach is robust and generalized by a standardized dataset and the real image dataset with a limited sample size(520 images).Hence,this method can be explored further for leukemia diagnosis having a limited number of dataset samples. 展开更多
关键词 leukemia diagnosis deep learning machine learning random forest XGBoost
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Damage Mechanism of CK2 and IKAROS in Philadelphia Like Acute Lymphoblastic Leukemia
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作者 Ignacio Vélez-Rodríguez Victoria Carranza-Aranda 《Journal of Biosciences and Medicines》 2024年第4期49-59,共11页
Acute lymphoblastic leukemia (ALL) is characterized by immature and poorly differentiated B lymphocytes in large numbers in the blood. B cells are distinct from the cell types involved in their development (common lym... Acute lymphoblastic leukemia (ALL) is characterized by immature and poorly differentiated B lymphocytes in large numbers in the blood. B cells are distinct from the cell types involved in their development (common lymphoid progenitor cells, pro-B cells, pre-B cells, and mature cells). The process of B cell maturation depends on precise communication within the cell: signals activate specific genes that are essential for proper development. Errors in this intricate signaling network can lead to issues with B cell function and contribute to disease. B-lineage acute lymphoid leukemias, malignancies of precursor-stage B lymphoid cells inhibit lymphoid differentiation, leading to abnormal cell proliferation and survival. The process of developing leukemia (leukemogenesis) can be triggered by an overproduction of both hematopoietic stem cells (the cells that form all blood cells) and the immature versions of white blood cells called lymphoblasts. Acute lymphoblastic leukemia (ALL) with the presence of the Philadelphia chromosome (ALL Ph) is classified as a high-risk manifestation of the disease, this chromosome is the product of the reciprocal translocation, whose product is a BCR-ABL fusion protein. It is a highly active tyrosine kinase that can transform hematopoietic cells into cytokine-independent. Hyperphosphorylation cascades inhibit the differentiating function of IKZF1 as a tumor suppressor gene which leads to an abnormal proliferation of B cells due to the presence of the Philadelphia chromosome;it inhibits the differentiating process, leukemogenesis involving immature B cells in the bloodstream can result from the uncontrolled growth and division of hematopoietic stem cells and immature lymphoblasts (the precursors to B cells). 展开更多
关键词 Acute Lymphoblastic leukemia IKAROS DEPHOSPHORYLATION Philadelphia Chromosome CK2
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RPRD1B/CREPT facilitates the progression of diffuse large B-cell lymphoma by inhibiting apoptosis through the NF-κB signaling pathway
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作者 Lu Xu Zhi-Hao Xie +5 位作者 Jun Li Shi Tao Fang-Li Ren Yin-Yin Wang Zhi-Jie Chang Xin-Bao Hao 《Asian Pacific Journal of Tropical Biomedicine》 SCIE CAS 2024年第7期307-318,共12页
Objective:To investigate the role of RPRD1B in the progression of diffuse large B-cell lymphoma(DLBCL)and its potential as a therapeutic target.Methods:This study analyzed RPRD1B expression in DLBCL and normal tissues... Objective:To investigate the role of RPRD1B in the progression of diffuse large B-cell lymphoma(DLBCL)and its potential as a therapeutic target.Methods:This study analyzed RPRD1B expression in DLBCL and normal tissues using public databases and assessed its prognostic impact through survival analysis.In vitro and in vivo experiments were conducted to explore the mechanisms by which RPRD1B influences tumor growth and apoptosis.Results:RPRD1B expression was significantly elevated in DLBCL compared to normal tissues and was associated with poor prognosis.In vitro and in vivo experiments demonstrated that RPRD1B promoted lymphoma cell proliferation and inhibited apoptosis through the NF-κB signaling pathway.Conclusions:RPRD1B plays a critical role in the progression of DLBCL by modulating apoptosis and cellular proliferation.Targeting RPRD1B may offer a novel therapeutic strategy for DLBCL,suggesting its potential as a prognostic marker and therapeutic target in hematological malignancies. 展开更多
关键词 RPRD1B RNAPⅡ Diffuse large b-cell lymphoma NF-ΚB APOPTOSIS
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Non-canonical BRAF variants and rearrangements in hairy cell leukemia
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作者 STEPHEN E.LANGABEER 《Oncology Research》 SCIE 2024年第9期1423-1427,共5页
Hairy cell leukemia(HCL)is an uncommon mature B-cell malignancy characterized by a typical morphology,immunophenotype,and clinical profile.The vast majority of HCL patients harbor the canonical BRAF V600E mutation whi... Hairy cell leukemia(HCL)is an uncommon mature B-cell malignancy characterized by a typical morphology,immunophenotype,and clinical profile.The vast majority of HCL patients harbor the canonical BRAF V600E mutation which has become a rationalized target of the subsequently deregulated RAS-RAF-MEK-MAPK signaling pathway in HCL patients who have relapsed or who are refractory to front-line therapy.However,several HCL patients with a classical phenotype display non-canonical BRAF mutations or rearrangements.These include sequence variants within alternative exons and an oncogenic fusion with the IGH gene.Care must be taken in the molecular diagnostic work-up of patients with typical HCL but without the BRAF V600E to include investigation of these uncommon mechanisms.Identification,functional characterization,and reporting of further such patients is likely to provide insights into the pathogenesis of HCL and enable rational selection of targeted inhibitors in such patients if required. 展开更多
关键词 Hairy cell leukemia BRAF Molecular diagnostics Targeted therapy
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Marine Predators Algorithm with Deep Learning-Based Leukemia Cancer Classification on Medical Images
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作者 Sonali Das Saroja Kumar Rout +5 位作者 Sujit Kumar Panda Pradyumna Kumar Mohapatra Abdulaziz S.Almazyad Muhammed Basheer Jasser Guojiang Xiong Ali Wagdy Mohamed 《Computer Modeling in Engineering & Sciences》 SCIE EI 2024年第10期893-916,共24页
In blood or bone marrow,leukemia is a form of cancer.A person with leukemia has an expansion of white blood cells(WBCs).It primarily affects children and rarely affects adults.Treatment depends on the type of leukemia... In blood or bone marrow,leukemia is a form of cancer.A person with leukemia has an expansion of white blood cells(WBCs).It primarily affects children and rarely affects adults.Treatment depends on the type of leukemia and the extent to which cancer has established throughout the body.Identifying leukemia in the initial stage is vital to providing timely patient care.Medical image-analysis-related approaches grant safer,quicker,and less costly solutions while ignoring the difficulties of these invasive processes.It can be simple to generalize Computer vision(CV)-based and image-processing techniques and eradicate human error.Many researchers have implemented computer-aided diagnosticmethods andmachine learning(ML)for laboratory image analysis,hopefully overcoming the limitations of late leukemia detection and determining its subgroups.This study establishes a Marine Predators Algorithm with Deep Learning Leukemia Cancer Classification(MPADL-LCC)algorithm onMedical Images.The projectedMPADL-LCC system uses a bilateral filtering(BF)technique to pre-process medical images.The MPADL-LCC system uses Faster SqueezeNet withMarine Predators Algorithm(MPA)as a hyperparameter optimizer for feature extraction.Lastly,the denoising autoencoder(DAE)methodology can be executed to accurately detect and classify leukemia cancer.The hyperparameter tuning process using MPA helps enhance leukemia cancer classification performance.Simulation results are compared with other recent approaches concerning various measurements and the MPADL-LCC algorithm exhibits the best results over other recent approaches. 展开更多
关键词 leukemia cancer medical imaging image classification deep learning marine predators algorithm
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Incidence and Survivability of Acute Lymphocytic Leukemia Patients in the United States: Analysis of SEER Data Set from 2000-2019
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作者 Ishan Ghosh Sudipto Mukherjee 《Journal of Cancer Therapy》 2024年第4期141-163,共23页
The main goal of this research is to assess the impact of race, age at diagnosis, sex, and phenotype on the incidence and survivability of acute lymphocytic leukemia (ALL) among patients in the United States. By takin... The main goal of this research is to assess the impact of race, age at diagnosis, sex, and phenotype on the incidence and survivability of acute lymphocytic leukemia (ALL) among patients in the United States. By taking these factors into account, the study aims to explore how existing cancer registry data can aid in the early detection and effective treatment of ALL in patients. Our hypothesis was that statistically significant correlations exist between race, age at which patients were diagnosed, sex, and phenotype of the ALL patients, and their rate of incidence and survivability data were evaluated using SEER*Stat statistical software from National Cancer Institute. Analysis of the incidence data revealed that a higher prevalence of ALL was among the Caucasian population. The majority of ALL cases (59%) occurred in patients aged between 0 to 19 years at the time of diagnosis, and 56% of the affected individuals were male. The B-cell phenotype was predominantly associated with ALL cases (73%). When analyzing survivability data, it was observed that the 5-year survival rates slightly exceeded the 10-year survival rates for the respective demographics. Survivability rates of African Americans patients were the lowest compared to Caucasian, Asian, Pacific Islanders, Alaskan Native, Native Americans and others. Survivability rates progressively decreased for older patients. Moreover, this study investigated the typical treatment methods applied to ALL patients, mainly comprising chemotherapy, with occasional supplementation of radiation therapy as required. The study demonstrated the considerable efficacy of chemotherapy in enhancing patients’ chances of survival, while those who remained untreated faced a less favorable prognosis from the disease. Although a significant amount of data and information exists, this study can help doctors in the future by diagnosing patients with certain characteristics. It will further assist the health care professionals in screening potential patients and early detection of cases. This could also save the lives of elderly patients who have a higher mortality rate from this disease. 展开更多
关键词 Acute Lymphocytic leukemia SURVIVABILITY INCIDENCE DEMOGRAPHY SEER Data Set
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Acute Leukemia in Niger: Epidemiological, Diagnostic and Therapeutic Aspects
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作者 Amadou Djibrilla-Almoustapha Badé Malam-Abdou +8 位作者 Abdourahamane Yacouba Moussa Souley Moustapha Maman Brah Moustapha Elhadji-Chefou Boubacar Marou-Soumana Samaila Aboubacar Ousseini Fanta Maman Rabiou Badé Oumarou Adamou-Chaibou 《Open Journal of Blood Diseases》 2024年第3期81-90,共10页
Objective: Improve the care of patients followed for acute leukemia in the Oncohematology department of the National Hospital of Niamey. Methods: This was a prospective study, over a period of 2 years from January 1, ... Objective: Improve the care of patients followed for acute leukemia in the Oncohematology department of the National Hospital of Niamey. Methods: This was a prospective study, over a period of 2 years from January 1, 2018 to December 31, 2019, in patients with acute leukemia in the Oncohematology department of the National Hospital of Niamey (HNN), whose diagnosis was made on a blood smear associated with a myelogram and immunophenotyping and who were consenting. Results: We collected 25 cases of acute leukemia confirmed by myelogram and immunophenotyping. The mean age of the patients was 31.32 years, with a predominance of women, a sex ratio of 0.92. Pupils and students were in the majority with 40% and most came from the Niamey region, i.e. 68%. Anemic syndrome was the most common clinical sign in 96%. ALL predominated in 64% of cases. On the blood count, the hyperleukocytosis was more marked in AML (mean white count: 197256.6 elts/mm3) than in ALL (137891.6 elts/mm3), it was the same for thrombocytopenia which is more marked in AML (75588.89/mm3) than in ALL (52156.25/mm3). Therapeutically, 52% of patients received chemotherapy. The mean overall survival was 16.223 ± 3.191 months, including a mean survival for AML of 6.853 ± 1200 months compared to 21.720 ± 5.920 months for ALL. Conclusion: Acute leukemia still remains a major problem in our context, due to the precariousness of limited financial, diagnostic and therapeutic resources. Thus reflecting in our results, the increasing number of cases, the diagnostic delay and the guarded prognosis. This is the reality in several other countries in the sub-region and even in certain developed countries. 展开更多
关键词 Acute leukemia ALL AML Hematology-Niamey National Hospital (HNN) NIGER
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