The monoclonal antibodies consist of an innovative form of immunotherapy,capable of defeating several diseases,such as cancer.It is an emergent and important theme,that advances evaluation,challenges,and future perspe...The monoclonal antibodies consist of an innovative form of immunotherapy,capable of defeating several diseases,such as cancer.It is an emergent and important theme,that advances evaluation,challenges,and future perspectives with high relevance to identify gaps in recent studies and to consolidate this general theme in only one research.Its action in Chronic and Acute Lymphoid Leukemia has been evaluated in several clinical trials,which were selected between 2022 and 2023,in order to understand better the monoclonal antibodies that were most studied.The biopharmaceutical compounds Ibrutinib,Obinutuzumab,Rituximab,Venetoclax,and Inotuzumab Ozogamicin were the ones that most appeared in the most recent publications,indicating the importance of amplifying the studies.The action mechanisms that are used imply that their combined use has more success in the disease remission,showing a lower recurrence,adverse effects,and toxicity.Besides the adverse effects and overwhelming prices of the treatment,these immunotherapies results are promising,amplifying the survival rates,improving the patient’s life quality,and resulting in a precision medicine,aiming a custom treatment.The future perspectives on this therapy consist of its application in the public health system,with patients being able to be submitted to this treatment without any costs and receive a better life quality.展开更多
Background:The outcomes of pediatric patients with acute lymphoblastic leukemia(ALL)remain far less than favorable.While apigenin is an anti-cancer agent,studies on the mechanism by which it regulates ALL cell cycle p...Background:The outcomes of pediatric patients with acute lymphoblastic leukemia(ALL)remain far less than favorable.While apigenin is an anti-cancer agent,studies on the mechanism by which it regulates ALL cell cycle progression are inadequate.Ferroptosis and AMP-activated protein kinase(AMPK)signaling are important processes for ALL patients.However,it remains unclear whether apigenin works by affecting AMPK and apoptosis.Materials and Methods:SUP-B15 and T-cell Jurkat ALL cells were treated with apigenin,and cell viability and apoptosis were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)and terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)assays,respectively.The thiobarbituric acid-reactive substances(TBARS)assay was used to evaluate lipid peroxidation.Intracellular Fe2+levels were measured using a commercial kit.Corresponding proteins were detected by western blotting.Results:Results showed that apigenin reduced cell viability and the levels of Ki67 and proliferating cell nuclear antigen(PCNA)expression in a concentration-dependent manner in both types of ALL cells.Apigenin also exerted anti-apoptotic effects on SUP-B15 and Jurkat cells.Apigenin activated AMP-activated protein kinase(AMPK)signaling and induced ferroptosis,and those effects were attenuated by inhibition of AMPK.Eventually,the reduced cell proliferation and increased cell apoptosis caused by apigenin in ALL cells were partly abolished by AMPK inhibition.Conclusion:In summary,apigenin exerted anti-leukemia activity in ALL cells,and that effect was partially achieved by activation of AMPK signaling.Our findings suggest apigenin as a potential drug for treatment of ALL.展开更多
Objective:Adverse-risk acute myeloid leukemia(AML)patients should receive allogeneic hematopoietic stem cell transplantation(allo-HSCT)at first complete remission(CR1).However,the influence of prior therapies[i.e.,ven...Objective:Adverse-risk acute myeloid leukemia(AML)patients should receive allogeneic hematopoietic stem cell transplantation(allo-HSCT)at first complete remission(CR1).However,the influence of prior therapies[i.e.,venetoclax plus azacitidine(VEN-AZA)or intensive chemotherapy(IC)]on post-transplant outcomes remains inconclusive.This multicenter,retrospective study compared the post-transplant outcomes between patients receiving VEN-AZA and those receiving IC before allo-HSCT.Methods:This study was based on the transplant database of TROPHY group.Consecutive adverse-risk AML patients receiving allo-HSCT from January 2021 to June 2023 were screened in five Chinese transplant centers.Patients were categorized into VEN-AZA group if they received venetoclax combined with azacitidine as first-line therapy followed by allo-HSCT.Patients who received first-line therapy consisting of a mainstay treatment of cytarabine and anthracycline followed by allo-HSCT were categorized into IC group.Results:In the total cohort,the 3-year probabilities of overall survival,leukemia-free survival,and event-free survival were better in the IC group than VEN-AZA group,particularly for patients with ASXL1 mutations or SF3B1 mutations.However,the survival of the VEN-AZA group was not superior to that of IC group in patients aged≥55 years or those with the hematopoietic cell transplantation-comorbidity index scores≥1 before allo-HSCT.After propensity score matching(median age:VEN-AZA group:57 years;IC group:55 years),only the probability of overall survival for the IC group was better than that of VEN-AZA group(93.6%vs.78.0%,P=0.034)at the 1-year follow-up;however,all of the other clinical outcomes were comparable between the VEN-AZA and IC groups.The TP53 mutation was independently associated with post-transplant relapse and survival.Conclusions:Our results suggest that IC remains the cornerstone of therapy,whereas VEN-AZA may also be used in younger patients and medically fit patients with adverse-risk AML who are receiving allo-HSCT in CR1.展开更多
Background:Growth differentiation factor 11(GDF11),a transforming growth factor-beta superfamily member,is a crucial protein involved in many differentiation processes in embryogenesis and morphogenesis,and it has bee...Background:Growth differentiation factor 11(GDF11),a transforming growth factor-beta superfamily member,is a crucial protein involved in many differentiation processes in embryogenesis and morphogenesis,and it has been extensively characterized due to its capacity to target poorly differentiated cells,including transformed or cancer cells.Aim:In the present work,we aimed to describe the effects on migration,proliferation,and metabolism in the T-cell acute lymphoblastic leukemia-derived cell line Jurkat.Methods:Based on previous evidence,we analyzed metabolic changes exerted by GDF11 and its relationship with the aggressive phenotype.Results:We found a profound impact on mitochondrial metabolism and reactive oxygen species content;these were related to a decrement in the expression of the transcription factor forkhead-box-protein P3(FOXP3),which is highly involved in aggressiveness in leukemia cells;this was verified by a decrement in invasion capacity exhibited by the Jurkat cells under the GDF11 treatment.Conclusion:The results position the GDF11 response as a good alternative in the search for new therapeutic options for these diseases.展开更多
A series of cyclopropane-1,1-diamide derivatives containing imidazo[1,2-a]pyridine were synthesized.The inhibitory effects of these compounds on FLT3-ITD kinase and their anti-proliferative activities against two acut...A series of cyclopropane-1,1-diamide derivatives containing imidazo[1,2-a]pyridine were synthesized.The inhibitory effects of these compounds on FLT3-ITD kinase and their anti-proliferative activities against two acute myeloid leukemia cell lines expressing FLT3-ITD were evaluated.With focused on the different substitutions of imidazo[1,2-a]pyridine,a preliminary exploration of the structure-activity relationship was conducted for 22 compounds.The results revealed that most compounds exhibited certain inhibitory effects on FLT3-ITD kinase with IC_(50) values below 0.5μmol·L^(-1).Among them,N-(4-fluorophenyl)-N-(4-(7-((2-morpholinoethyl)carbamoyl)imidazo[1,2-a]pyridine-3-carbonyl)phenyl)cyclopropane-1,1-dicarboxamide(12a)demonstrated the most potent FLT3-ITD kinase inhibitory activity and the strongest anti-proliferative effect on the MV4-11 and MOLM-13 cell lines expressing FLT3-ITD with IC50 values of 0.06 and 0.2μmol·L^(-1),respectively.Moreover,compound 12a did not exhibit anti-proliferative activity against cell lines without FLT3 mutations,such as THP-1,HCT-116,A549,HepG2,K562,and MCF-7,and it displayed non-cytotoxicity towards normal human renal tubular epithelial cells(HK-2),human liver progenitor cells(HepaRG),and HEK293(human embryonic kidney cells).Although 12a exhibits inferior inhibitory activity against FLT3-ITD kinase and anti-tumor cell proliferation compared to C abozantinib in this study,it can provide a reference for further research into FLT3-ITD inhibitors.展开更多
Background: Acute Leukemia is the most common childhood cancer, with two main types: ALL and AML. In Tanzania, recent improvements in treatment and survival have been noted, but the latest data is from 2013. This stud...Background: Acute Leukemia is the most common childhood cancer, with two main types: ALL and AML. In Tanzania, recent improvements in treatment and survival have been noted, but the latest data is from 2013. This study will update survival and relapse information from 2013 to 2020 to help enhance future treatment strategies. Methodology: This study was conducted at two tertiary hospitals in Tanzania. The study analyzed data from children diagnosed with Acute Leukemia between January 2015 to December 2020. Patient data were collected via questionnaires and analyzed using STATA software. Results: This study included a total of 95 participants 64 had age less than 10 years and majority were males 56.8%, 55 had duration of symptoms for more than 1 month 66 had ALL, 49 had attained remission, the overall three years survival was 44.2% with those children with no health insurance having high risk of dying, rate of relapse was 18.4%, with those diagnosed with B-ALL having low risk of relapse. Conclusion: This study provides insights into survival and relapse predictors for childhood leukemia in northern Tanzania. It found an overall survival rate of 44.2%, with health insurance and minimal residual disease after induction being key predictors of survival. The relapse rate was 18.4%, with health insurance linked to a lower relapse risk. Health insurance emerged as a strong predictor of better survival, leading to the recommendation that all children should have health insurance. Additionally, the study suggests that policymakers should support the expansion of global health coverage in Tanzania.展开更多
Venetoclax(Vene),a BCL-2 inhibitor,is widely used as a chemotherapeutic drug in acute myeloid leukemia(AML).However,its treatment specificity for leukemia cells is limited,often leading to side effects and treatment r...Venetoclax(Vene),a BCL-2 inhibitor,is widely used as a chemotherapeutic drug in acute myeloid leukemia(AML).However,its treatment specificity for leukemia cells is limited,often leading to side effects and treatment resistance.In this study,we utilized L-phenylalanine as an efficient nanocarrier to enhance the delivery of Vene,forming the complex Vene@8P6.This complex was then applied to AML mouse models and human AML cell lines.The in vitro analysis showed that THP-1 and HL60 cells rapidly absorbed the Vene@8P6 nanoparticles.This absorption resulted in severe DNA damage,increased reactive oxygen species(ROS)production,elevated apoptosis rates,and decreased cell proliferation compared to the administration of Vene alone.In vivo studies demonstrated that Vene@8P6 more efficiently targeted leukemia cells than normal hematopoietic cells within the bone marrow and other major organs in AML mice,as evidenced by bioluminescence imaging and flow cytometry analysis.Furthermore,Vene@8P6 treatment resulted in reduced drug side effects and improved therapeutic efficacy in AML mice.Overall,Vene@8P6 represents a novel and efficient therapeutic agent for AML,offering enhanced leukemia target specificity,reduced side effects,and improved treatment outcomes.展开更多
Tyrosine kinase inhibitors(TKIs)are used to treat patients with chronic myelogenous leukemia(CML),leading to a nearly normal life expectancy.Sprycel(dasatinib)-induced chylothorax has rarely been reported in patients ...Tyrosine kinase inhibitors(TKIs)are used to treat patients with chronic myelogenous leukemia(CML),leading to a nearly normal life expectancy.Sprycel(dasatinib)-induced chylothorax has rarely been reported in patients undergoing CML treatment.We report a 10-year case history of chronic chylothorax that persisted despite discontinuation of dasatinib in a patient with otherwise excellent results after switching to another TKI.Herein,we discuss a conservative treatment approach that uses symptom-based thoracentesis instead of surgical ligation of the thoracic duct.This approach may reduce patient morbidity and prevent the need for complex surgical procedures.TKIs have revolutionized CML treatment;however,these powerful medications are not without patient morbidity.展开更多
BACKGROUND Colon cancer is a common malignancy of the digestive tract.An estimated 1148515 new cases of colon cancer were reported in 2020 worldwide.Chronic myeloid leukemia(CML)is a malignant tumor formed by the clon...BACKGROUND Colon cancer is a common malignancy of the digestive tract.An estimated 1148515 new cases of colon cancer were reported in 2020 worldwide.Chronic myeloid leukemia(CML)is a malignant tumor formed by the clonal proliferation of bone marrow hematopoietic stem cells,with an annual incidence rate of 1-2 cases per 100000 people worldwide.Leukemia can be secondary to solid tumors,and vice versa.Reports on CML secondary malignant tumors account for 8.7% but CML secondary to malignancy is extremely rare.Therapy-related CML is a rare but potentially fatal adverse event of chemotherapy or radiotherapy.Herein,we report a case of CML with colon cancer and discuss this unique patient popu-lation.Our findings can provide effective raw data and guidance for the diagnosis of this clinical disease.CML in patients with colon cancer is extremely rare.Secondary hematological tumors may be multifactorial,and the exact mechanism is currently unknown.Owing to the slow progression of the disease,patients with CML show no sy-mptoms in the early stage.However,with disease progression,obvious but non-specific symptoms may appear,including fever,anemia,bleeding tendency,and hypertrophy.Therefore,complete blood count monitoring for routine examination is recommended after cancer treatment for early detection of occult hematological tumors.展开更多
The gut microbiome plays a pivotal role in immune homeostasis and systemic inflammatory regulation,both of which are critically involved in the pathogenesis and progression of pediatric leukemias.Recent evidence revea...The gut microbiome plays a pivotal role in immune homeostasis and systemic inflammatory regulation,both of which are critically involved in the pathogenesis and progression of pediatric leukemias.Recent evidence reveals that children with leukemia often exhibit distinct gut microbiome profiles at diagnosis,marked by reduced microbial diversity and the enrichment of pro-inflammatory taxa such as Enterococcus and Streptococcus.This microbial dysbiosis may promote leukemogenesis by disrupting immune regulation and driving chronic inflammation.Chemotherapy significantly alters the gut microbiome,inducing dysbiosis characterized by a loss of beneficial commensals and the dominance of pathobionts.Specific microbial signatures,such as the enrichment of Bacteroides,correlate with reduced inflammation and improved prognosis,underscoring the gut microbiome's prognostic value.Emerging therapies,including dietary adjustments,probiotics,and fecal gut microbiome transplantation,aim to restore microbial balance and reduce treatment-related complications.Moreover,gut microbiome profiling shows potential for identifying biomarkers linked to leukemia predisposition,paving the way for early diagnosis and tailored preventive strategies.This mini-review explores recent advancements in understanding the influence of the gut microbiome on pediatric leukemias,emphasizing its role as both a therapeutic target and a prognostic biomarker.Integrating gut microbiome research into clinical practice may help optimize treatment outcomes and improve quality of life for children with leukemia.展开更多
Objective:To evaluate the immune function and safety of Venetoclax combined with Azacitidine in the treatment of elderly patients with acute myeloid leukemia(AML).Methods:Sixty-eight elderly AML patients who visited t...Objective:To evaluate the immune function and safety of Venetoclax combined with Azacitidine in the treatment of elderly patients with acute myeloid leukemia(AML).Methods:Sixty-eight elderly AML patients who visited the hospital from January 2021 to December 2024 were selected as samples and randomly divided into two groups.Group A was treated with Venetoclax and Azacitidine,while Group B was treated with Azacitidine alone.Immune indicators,inflammatory factors,tumor markers,and adverse reactions were compared between the two groups.Results:The levels of CD3+,CD4+,and CD8+in Group A were higher than those in Group B(P<0.05).The tumor necrosis factor-α(TNF-α)level in Group A was lower than that in Group B,while the interferon-γ(IFN-γ)level was higher(P<0.05).The levels of cyclooxygenase-2(COX-2),lactate dehydrogenase(LDH),and vascular endothelial growth factor(VEGF)in Group A were lower than those in Group B(P<0.05).The adverse reaction rate in Group A was lower than that in Group B(P<0.05).Conclusion:The combination of Venetoclax and Azacitidine in the treatment of elderly AML patients can improve immune function,inhibit inflammation,delay disease progression,and is safe and efficient.展开更多
Patients with leukemia often suffer from the combined effects of cancer-related fatigue(CRF)and subthreshold depression,which mutually exacerbate each other in a vicious cycle.In this editorial,we comment on the artic...Patients with leukemia often suffer from the combined effects of cancer-related fatigue(CRF)and subthreshold depression,which mutually exacerbate each other in a vicious cycle.In this editorial,we comment on the article by Liu et al,published in the World Journal of Psychiatry.We further elucidate the profound impact of subthreshold depressive symptoms on the experience of CRF and complications in patients with leukemia.This editorial highlights the importance of early identification and treatment of subclinical depression,and advocates for a multidisciplinary and integrated treatment approach that includes social support,psychological interventions,and individualized treatment plans.Future research needs to explore the biological mechanisms underlying the interaction between the two to develop more effective prevention and treatment strategies.展开更多
Objective:To investigate the efficacy of a tripartite collaborative nursing intervention in enhancing resilience among families of pediatric leukemia patients.Methods:Based on Walsh’s family resilience theory and col...Objective:To investigate the efficacy of a tripartite collaborative nursing intervention in enhancing resilience among families of pediatric leukemia patients.Methods:Based on Walsh’s family resilience theory and collaborative nursing principles,and after reviewing a large amount of literature,a tripartite intervention was constructed,which was led by the nursing team,coordinated by medical social workers,and supported by volunteers.Caregivers of pediatric hematology inpatients at a tertiary-level Class A hospital were selected as research subjects.which were divided into a control group(n=30)and an experimental group(n=30)according to a randomized block design.The control group are treated with standard nursing care,which included health education,counseling,and psychological support from nurses.The experimental group,in addition,was provided with a tripartite collaborative nursing intervention for 3 months.Results:The family resilience level,social support,and family function scores of the experimental group were higher than those of the control group,and the differences were statistically significant(P≤0.05).Conclusion:The implementation of tripartite collaborative nursing intervention improves the resilience of families of children suffered from leukemia.展开更多
The clinical efficacy of immunotherapy in acute myeloid leukemia(AML)remains significantly limited by early relapse and treatment-associated toxicities.This review examines recent advances in antibody-and cell-based i...The clinical efficacy of immunotherapy in acute myeloid leukemia(AML)remains significantly limited by early relapse and treatment-associated toxicities.This review examines recent advances in antibody-and cell-based immunotherapies for AML,focusing on established targets(CD33,CD123,and CLL1)as well as emerging targets(including CD7,CD70,CD38,and FLT3).Therapeutic modalities discussed include immunoconjugates,bispecific T-cell engagers and chimeric antigen receptor T(CAR-T)cells.Furthermore,we summarize the current challenges impeding the success of immunotherapy in AML and propose strategies to enhance its efficacy.These include combination therapies,structural optimization of CAR constructs,functional enhancement of CAR-T cells,identification of novel targets,and the development of next-generation cellular therapies.Collectively,these approaches aim to offer new insights for improving immunotherapeutic outcomes in AML.展开更多
BACKGROUND The introduction of pegaspargase has greatly advanced the treatment of acute lymphoblastic leukemia(ALL).In the literature,only one case of pegaspargaseinduced multiple organ failure has been reported,and t...BACKGROUND The introduction of pegaspargase has greatly advanced the treatment of acute lymphoblastic leukemia(ALL).In the literature,only one case of pegaspargaseinduced multiple organ failure has been reported,and the patient died due to multiple organ failure.CASE SUMMARY Herein,we present a rare case of a 40-year-old man with ALL who developed multiple organ failure after treatment with pegaspargase.The patient had two rare phenomena reflecting poor prognosis,including the discrepancy between clinical manifestations and liver function and persistently low alpha-fetoprotein(AFP)levels from subacute liver failure.However,the patient was successfully treated using a multidisciplinary team approach.CONCLUSION This is the first case report of successful treatment of pegaspargase-induced multiple organ failure.The findings emphasize the importance of a multidisciplinary team approach in treating pegaspargase-induced multiple organ failure.展开更多
BACKGROUND The prognosis for acute myeloid leukemia(AML)remains poor,underscoring the need for a deeper understanding of its underlying molecular mechanisms.AIM To assess the significance of SOX11 gene expression in t...BACKGROUND The prognosis for acute myeloid leukemia(AML)remains poor,underscoring the need for a deeper understanding of its underlying molecular mechanisms.AIM To assess the significance of SOX11 gene expression in the clinical features,response to treatment,and survival outcomes of adult patients with AML.METHODS This retrospective study enrolled 102 adults with AML.SOX11 gene expression in bone marrow samples was measured using real-time PCR.Data were correlated to the patients’clinical features,response to treatment,and survival rates.RESULTS Increased SOX11 expression was significantly associated with the presence of the FLT3-ITD mutation(P<0.001),the FAB-M2 subtype(P=0.008),and cytogenetic abnormalities(P=0.011).However,no significant association was found between SOX11 expression and other clinical laboratory parameters,complete remission,disease-free survival,or overall survival.CONCLUSION SOX11 expression may serve as a marker to identify specific subsets of AML patients who could benefit from intensive targeted chemotherapy.展开更多
BACKGROUND Acute myeloid leukemia(AML)is a complicated disease with uncontrolled hematopoietic precursor proliferation induced by various genetic alterations.Runt-related transcription factor-1(RUNX1)is commonly disru...BACKGROUND Acute myeloid leukemia(AML)is a complicated disease with uncontrolled hematopoietic precursor proliferation induced by various genetic alterations.Runt-related transcription factor-1(RUNX1)is commonly disrupted by chromosomal translocations in hematological malignancies.AIM To characterize RUNX1 gene rearrangements and copy number variations in newly diagnosed adult AML patients,with an emphasis on the impact of clinical and laboratory features on the outcome.METHODS Fluorescence in situ hybridization was used to test RUNX1 gene alterations in 77 newly diagnosed adult AML cases.NPM1,FLT3/ITD,FLT3/TKD,and KIT mutations were tested by PCR.Prognostic clinical and laboratory findings were studied in relation to RUNX1 alterations.RESULTS RUNX1 abnormalities were detected by fluorescence in situ hybridization in 41.6%of patients:20.8%had translocations,22.1%had amplification,and 5.2%had deletion.Translocations prevailed in AML-M2(P=0.019)with a positive expression of myeloperoxidase(P=0.031),whereas deletions dominated in M4 and M5 subtypes(P=0.008)with a positive association with CD64 expression(P=0.05).The modal chromosomal number was higher in cases having amplifications(P=0.007)and lower in those with deletions(P=0.008).RUNX1 abnormalities were associated with complex karyotypes(P<0.001)and were mutually exclusive of NPM1 mutations.After 44 months of follow-up,RUNX1 abnormalities affected neither patients’response to treatment nor overall survival.CONCLUSION RUNX1 abnormalities were mutually exclusive of NPM1 mutations.RUNX1 abnormalities affected neither patients’response to treatment nor overall survival.展开更多
Myristica is a classic traditional Chinese medicine widely used for leukemia treatment.However,its main active ingredients and underlying mechanisms of action remain poorly understood.In this study,we comprehensively ...Myristica is a classic traditional Chinese medicine widely used for leukemia treatment.However,its main active ingredients and underlying mechanisms of action remain poorly understood.In this study,we comprehensively investigated the mechanisms by which Myristica exerted effects on radiation-induced myeloid leukemia(RIML)using molecular docking and network pharmacology.The active ingredients in Myristica were further identified via TCMSP database,potential Myristica-related targets were extracted from GEO,GeneCards,OMIM,and DisGeNET databases,a protein-protein interaction(PPI)network was constructed to screen key targets(followed by GO and KEGG enrichment analyses),and finally the binding affinity between active compounds and key targets was verified.The screening results identified 9 active substances,including Kudos,isoguaiacin,galbacin,and others.Topological analysis of the PPI network revealed that PARP1,ESR1,MTOR,MDM2,HIF1A,and ALB were key targets.GO enrichment analysis showed that these targets were mainly involved in biological processes such as DNA repair,cell cycle regulation,apoptosis,and oxidative stress response.KEGG pathway enrichment analysis indicated that Myristica might exert anti-leukemia effects by regulating signaling pathways such as PI3K-Akt,mTOR,and HIF-1.展开更多
Background:Acute Myeloid Leukemia(AML)is a highly aggressive clonal hematological malignancy with limited treatment options.This study aimed to evaluate the therapeutic potential of nigericin,a polyether ionophore der...Background:Acute Myeloid Leukemia(AML)is a highly aggressive clonal hematological malignancy with limited treatment options.This study aimed to evaluate the therapeutic potential of nigericin,a polyether ionophore derived from Streptomyces DASNCL-29,as a mitochondrial-targeted agent for AML treatment.Methods:Nigericin was isolated from Streptomyces DASNCL-29 and characterized via chromatography and NMR.Its cytotoxicity was tested in MOLM13(sensitive and venetoclax-resistant)and HL60(sensitive and cytarabine-resistant)cells using the MTT assay.Mitochondrial dysfunction was assessed by measuring reactive oxygen species(ROS),mitochondrial membrane potential(Δψm),and mitochondrial mass.Apoptosis was evaluated with Annexin V/PI assays and immunoblotting,while proteomic analysis was conducted using Liquid Chromatography-Tandem Mass Spectrometry(LC-MS/MS)to identify differentially regulated proteins.Results:Nigericin demonstrated potent cytotoxicity with IC50 values of 57.02 nM in MOLM13-sensitive,35.29 nM in MOLM13-resistant,20.49 nM in HL60-sensitive,and 1.197 nM in HL60-cytarabine-resistant cells.Apoptosis was confirmed by Annexin V/PI staining and caspase-3/PARP cleavage,along with MCL-1 downregulation.Mitochondrial dysfunction was evident from increased ROS,reducedΔψm,and decreased mitochondrial mass.Proteomic profiling identified 264 dysregulated proteins,including a 3.8-fold upregulation of Succinate Dehydrogenase[Ubiquinone]Flavoprotein Subunit A(SDHA).Conclusion:Nigericin induces apoptosis in AML cells by disrupting mitochondrial function and enhancing oxidative stress.Its nanomolar potency highlights the need for further mechanistic studies and in vivo evaluations to explore its potential in AML treatment.展开更多
Acute lymphoblastic leukemia(ALL)is characterized by overgrowth of immature lymphoid cells in the bone marrow at the expense of normal hematopoiesis.One of the most prioritized tasks is the early and correct diagnosis...Acute lymphoblastic leukemia(ALL)is characterized by overgrowth of immature lymphoid cells in the bone marrow at the expense of normal hematopoiesis.One of the most prioritized tasks is the early and correct diagnosis of this malignancy;however,manual observation of the blood smear is very time-consuming and requires labor and expertise.Transfer learning in deep neural networks is of growing importance to intricate medical tasks such as medical imaging.Our work proposes an application of a novel ensemble architecture that puts together Vision Transformer and EfficientNetV2.This approach fuses deep and spatial features to optimize discriminative power by selecting features accurately,reducing redundancy,and promoting sparsity.Besides the architecture of the ensemble,the advanced feature selection is performed by the Frog-Snake Prey-Predation Relationship Optimization(FSRO)algorithm.FSRO prioritizes the most relevant features while dynamically reducing redundant and noisy data,hence improving the efficiency and accuracy of the classification model.We have compared our method for feature selection against state-of-the-art techniques and recorded an accuracy of 94.88%,a recall of 94.38%,a precision of 96.18%,and an F1-score of 95.63%.These figures are therefore better than the classical methods for deep learning.Though our dataset,collected from four different hospitals,is non-standard and heterogeneous,making the analysis more challenging,although computationally expensive,our approach proves diagnostically superior in cancer detection.Source codes and datasets are available on GitHub.展开更多
文摘The monoclonal antibodies consist of an innovative form of immunotherapy,capable of defeating several diseases,such as cancer.It is an emergent and important theme,that advances evaluation,challenges,and future perspectives with high relevance to identify gaps in recent studies and to consolidate this general theme in only one research.Its action in Chronic and Acute Lymphoid Leukemia has been evaluated in several clinical trials,which were selected between 2022 and 2023,in order to understand better the monoclonal antibodies that were most studied.The biopharmaceutical compounds Ibrutinib,Obinutuzumab,Rituximab,Venetoclax,and Inotuzumab Ozogamicin were the ones that most appeared in the most recent publications,indicating the importance of amplifying the studies.The action mechanisms that are used imply that their combined use has more success in the disease remission,showing a lower recurrence,adverse effects,and toxicity.Besides the adverse effects and overwhelming prices of the treatment,these immunotherapies results are promising,amplifying the survival rates,improving the patient’s life quality,and resulting in a precision medicine,aiming a custom treatment.The future perspectives on this therapy consist of its application in the public health system,with patients being able to be submitted to this treatment without any costs and receive a better life quality.
基金supported by The National Natural Science Foundation of China(No.31902283)Research Foundation for Master students at the Affiliated Hospital of Zunyi Medical College(No.22-2018).
文摘Background:The outcomes of pediatric patients with acute lymphoblastic leukemia(ALL)remain far less than favorable.While apigenin is an anti-cancer agent,studies on the mechanism by which it regulates ALL cell cycle progression are inadequate.Ferroptosis and AMP-activated protein kinase(AMPK)signaling are important processes for ALL patients.However,it remains unclear whether apigenin works by affecting AMPK and apoptosis.Materials and Methods:SUP-B15 and T-cell Jurkat ALL cells were treated with apigenin,and cell viability and apoptosis were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)and terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)assays,respectively.The thiobarbituric acid-reactive substances(TBARS)assay was used to evaluate lipid peroxidation.Intracellular Fe2+levels were measured using a commercial kit.Corresponding proteins were detected by western blotting.Results:Results showed that apigenin reduced cell viability and the levels of Ki67 and proliferating cell nuclear antigen(PCNA)expression in a concentration-dependent manner in both types of ALL cells.Apigenin also exerted anti-apoptotic effects on SUP-B15 and Jurkat cells.Apigenin activated AMP-activated protein kinase(AMPK)signaling and induced ferroptosis,and those effects were attenuated by inhibition of AMPK.Eventually,the reduced cell proliferation and increased cell apoptosis caused by apigenin in ALL cells were partly abolished by AMPK inhibition.Conclusion:In summary,apigenin exerted anti-leukemia activity in ALL cells,and that effect was partially achieved by activation of AMPK signaling.Our findings suggest apigenin as a potential drug for treatment of ALL.
基金supported by the Beijing Natural Science Foundation(No.Z230016)the National Key Research and Development Program of China(No.2022YFC 2502606)+4 种基金the Major Program of the National Natural Science Foundation of China(No.82293630)the Peking University Medicine Fund for the World’s Leading Discipline or Discipline Cluster Development(No.71003Y3035)the Plan Project of Tongzhou Municipal Science and Technology(No.KJ2024CX045)the National Natural Science Foundation of China(No.82170208)the Fundamental Research Funds for the Central Universities。
文摘Objective:Adverse-risk acute myeloid leukemia(AML)patients should receive allogeneic hematopoietic stem cell transplantation(allo-HSCT)at first complete remission(CR1).However,the influence of prior therapies[i.e.,venetoclax plus azacitidine(VEN-AZA)or intensive chemotherapy(IC)]on post-transplant outcomes remains inconclusive.This multicenter,retrospective study compared the post-transplant outcomes between patients receiving VEN-AZA and those receiving IC before allo-HSCT.Methods:This study was based on the transplant database of TROPHY group.Consecutive adverse-risk AML patients receiving allo-HSCT from January 2021 to June 2023 were screened in five Chinese transplant centers.Patients were categorized into VEN-AZA group if they received venetoclax combined with azacitidine as first-line therapy followed by allo-HSCT.Patients who received first-line therapy consisting of a mainstay treatment of cytarabine and anthracycline followed by allo-HSCT were categorized into IC group.Results:In the total cohort,the 3-year probabilities of overall survival,leukemia-free survival,and event-free survival were better in the IC group than VEN-AZA group,particularly for patients with ASXL1 mutations or SF3B1 mutations.However,the survival of the VEN-AZA group was not superior to that of IC group in patients aged≥55 years or those with the hematopoietic cell transplantation-comorbidity index scores≥1 before allo-HSCT.After propensity score matching(median age:VEN-AZA group:57 years;IC group:55 years),only the probability of overall survival for the IC group was better than that of VEN-AZA group(93.6%vs.78.0%,P=0.034)at the 1-year follow-up;however,all of the other clinical outcomes were comparable between the VEN-AZA and IC groups.The TP53 mutation was independently associated with post-transplant relapse and survival.Conclusions:Our results suggest that IC remains the cornerstone of therapy,whereas VEN-AZA may also be used in younger patients and medically fit patients with adverse-risk AML who are receiving allo-HSCT in CR1.
基金funded by a grant from the Consejo Nacional de humanidades Ciencia y Tecnología(Conahcyt).Fronteras de la Ciencia 1320,Infra-2017280788Universidad Autónoma Metropolitana-Iztapalapa.
文摘Background:Growth differentiation factor 11(GDF11),a transforming growth factor-beta superfamily member,is a crucial protein involved in many differentiation processes in embryogenesis and morphogenesis,and it has been extensively characterized due to its capacity to target poorly differentiated cells,including transformed or cancer cells.Aim:In the present work,we aimed to describe the effects on migration,proliferation,and metabolism in the T-cell acute lymphoblastic leukemia-derived cell line Jurkat.Methods:Based on previous evidence,we analyzed metabolic changes exerted by GDF11 and its relationship with the aggressive phenotype.Results:We found a profound impact on mitochondrial metabolism and reactive oxygen species content;these were related to a decrement in the expression of the transcription factor forkhead-box-protein P3(FOXP3),which is highly involved in aggressiveness in leukemia cells;this was verified by a decrement in invasion capacity exhibited by the Jurkat cells under the GDF11 treatment.Conclusion:The results position the GDF11 response as a good alternative in the search for new therapeutic options for these diseases.
文摘A series of cyclopropane-1,1-diamide derivatives containing imidazo[1,2-a]pyridine were synthesized.The inhibitory effects of these compounds on FLT3-ITD kinase and their anti-proliferative activities against two acute myeloid leukemia cell lines expressing FLT3-ITD were evaluated.With focused on the different substitutions of imidazo[1,2-a]pyridine,a preliminary exploration of the structure-activity relationship was conducted for 22 compounds.The results revealed that most compounds exhibited certain inhibitory effects on FLT3-ITD kinase with IC_(50) values below 0.5μmol·L^(-1).Among them,N-(4-fluorophenyl)-N-(4-(7-((2-morpholinoethyl)carbamoyl)imidazo[1,2-a]pyridine-3-carbonyl)phenyl)cyclopropane-1,1-dicarboxamide(12a)demonstrated the most potent FLT3-ITD kinase inhibitory activity and the strongest anti-proliferative effect on the MV4-11 and MOLM-13 cell lines expressing FLT3-ITD with IC50 values of 0.06 and 0.2μmol·L^(-1),respectively.Moreover,compound 12a did not exhibit anti-proliferative activity against cell lines without FLT3 mutations,such as THP-1,HCT-116,A549,HepG2,K562,and MCF-7,and it displayed non-cytotoxicity towards normal human renal tubular epithelial cells(HK-2),human liver progenitor cells(HepaRG),and HEK293(human embryonic kidney cells).Although 12a exhibits inferior inhibitory activity against FLT3-ITD kinase and anti-tumor cell proliferation compared to C abozantinib in this study,it can provide a reference for further research into FLT3-ITD inhibitors.
文摘Background: Acute Leukemia is the most common childhood cancer, with two main types: ALL and AML. In Tanzania, recent improvements in treatment and survival have been noted, but the latest data is from 2013. This study will update survival and relapse information from 2013 to 2020 to help enhance future treatment strategies. Methodology: This study was conducted at two tertiary hospitals in Tanzania. The study analyzed data from children diagnosed with Acute Leukemia between January 2015 to December 2020. Patient data were collected via questionnaires and analyzed using STATA software. Results: This study included a total of 95 participants 64 had age less than 10 years and majority were males 56.8%, 55 had duration of symptoms for more than 1 month 66 had ALL, 49 had attained remission, the overall three years survival was 44.2% with those children with no health insurance having high risk of dying, rate of relapse was 18.4%, with those diagnosed with B-ALL having low risk of relapse. Conclusion: This study provides insights into survival and relapse predictors for childhood leukemia in northern Tanzania. It found an overall survival rate of 44.2%, with health insurance and minimal residual disease after induction being key predictors of survival. The relapse rate was 18.4%, with health insurance linked to a lower relapse risk. Health insurance emerged as a strong predictor of better survival, leading to the recommendation that all children should have health insurance. Additionally, the study suggests that policymakers should support the expansion of global health coverage in Tanzania.
基金the National Natural Science Foundation of China(No.52173150 to J.Wu)the National Natural Science Foundation of China(No.82370164 to C.Chen)+5 种基金Guangzhou Science and Technology Program City-University Joint Funding Project(No.2023A03J0001 to J.Wu)the Affiliated Qingyuan Hospital of Guangzhou Medical University Open Project Fund(No.202301–211 to J.Wu)Sanming Project of Medicine in Shenzhen(No.SZSM201911004 to D.Lin and M.Zhao)National Natural Science Foundation of China(No.92268205 to D.Lin)Doctoral Scientific Research Foundation of Changzhi Medical College,China(to Z.Zhao)Post-doctoral Science Foundation(No.2022M723670 to L.Wang)。
文摘Venetoclax(Vene),a BCL-2 inhibitor,is widely used as a chemotherapeutic drug in acute myeloid leukemia(AML).However,its treatment specificity for leukemia cells is limited,often leading to side effects and treatment resistance.In this study,we utilized L-phenylalanine as an efficient nanocarrier to enhance the delivery of Vene,forming the complex Vene@8P6.This complex was then applied to AML mouse models and human AML cell lines.The in vitro analysis showed that THP-1 and HL60 cells rapidly absorbed the Vene@8P6 nanoparticles.This absorption resulted in severe DNA damage,increased reactive oxygen species(ROS)production,elevated apoptosis rates,and decreased cell proliferation compared to the administration of Vene alone.In vivo studies demonstrated that Vene@8P6 more efficiently targeted leukemia cells than normal hematopoietic cells within the bone marrow and other major organs in AML mice,as evidenced by bioluminescence imaging and flow cytometry analysis.Furthermore,Vene@8P6 treatment resulted in reduced drug side effects and improved therapeutic efficacy in AML mice.Overall,Vene@8P6 represents a novel and efficient therapeutic agent for AML,offering enhanced leukemia target specificity,reduced side effects,and improved treatment outcomes.
文摘Tyrosine kinase inhibitors(TKIs)are used to treat patients with chronic myelogenous leukemia(CML),leading to a nearly normal life expectancy.Sprycel(dasatinib)-induced chylothorax has rarely been reported in patients undergoing CML treatment.We report a 10-year case history of chronic chylothorax that persisted despite discontinuation of dasatinib in a patient with otherwise excellent results after switching to another TKI.Herein,we discuss a conservative treatment approach that uses symptom-based thoracentesis instead of surgical ligation of the thoracic duct.This approach may reduce patient morbidity and prevent the need for complex surgical procedures.TKIs have revolutionized CML treatment;however,these powerful medications are not without patient morbidity.
基金Supported by the Innovation Platform and talent program of Hunan Province,No.2021SK4050the Natural Science Foundation of Hunan Province,No.2023JJ30608 and No.2023JJ30609.
文摘BACKGROUND Colon cancer is a common malignancy of the digestive tract.An estimated 1148515 new cases of colon cancer were reported in 2020 worldwide.Chronic myeloid leukemia(CML)is a malignant tumor formed by the clonal proliferation of bone marrow hematopoietic stem cells,with an annual incidence rate of 1-2 cases per 100000 people worldwide.Leukemia can be secondary to solid tumors,and vice versa.Reports on CML secondary malignant tumors account for 8.7% but CML secondary to malignancy is extremely rare.Therapy-related CML is a rare but potentially fatal adverse event of chemotherapy or radiotherapy.Herein,we report a case of CML with colon cancer and discuss this unique patient popu-lation.Our findings can provide effective raw data and guidance for the diagnosis of this clinical disease.CML in patients with colon cancer is extremely rare.Secondary hematological tumors may be multifactorial,and the exact mechanism is currently unknown.Owing to the slow progression of the disease,patients with CML show no sy-mptoms in the early stage.However,with disease progression,obvious but non-specific symptoms may appear,including fever,anemia,bleeding tendency,and hypertrophy.Therefore,complete blood count monitoring for routine examination is recommended after cancer treatment for early detection of occult hematological tumors.
文摘The gut microbiome plays a pivotal role in immune homeostasis and systemic inflammatory regulation,both of which are critically involved in the pathogenesis and progression of pediatric leukemias.Recent evidence reveals that children with leukemia often exhibit distinct gut microbiome profiles at diagnosis,marked by reduced microbial diversity and the enrichment of pro-inflammatory taxa such as Enterococcus and Streptococcus.This microbial dysbiosis may promote leukemogenesis by disrupting immune regulation and driving chronic inflammation.Chemotherapy significantly alters the gut microbiome,inducing dysbiosis characterized by a loss of beneficial commensals and the dominance of pathobionts.Specific microbial signatures,such as the enrichment of Bacteroides,correlate with reduced inflammation and improved prognosis,underscoring the gut microbiome's prognostic value.Emerging therapies,including dietary adjustments,probiotics,and fecal gut microbiome transplantation,aim to restore microbial balance and reduce treatment-related complications.Moreover,gut microbiome profiling shows potential for identifying biomarkers linked to leukemia predisposition,paving the way for early diagnosis and tailored preventive strategies.This mini-review explores recent advancements in understanding the influence of the gut microbiome on pediatric leukemias,emphasizing its role as both a therapeutic target and a prognostic biomarker.Integrating gut microbiome research into clinical practice may help optimize treatment outcomes and improve quality of life for children with leukemia.
文摘Objective:To evaluate the immune function and safety of Venetoclax combined with Azacitidine in the treatment of elderly patients with acute myeloid leukemia(AML).Methods:Sixty-eight elderly AML patients who visited the hospital from January 2021 to December 2024 were selected as samples and randomly divided into two groups.Group A was treated with Venetoclax and Azacitidine,while Group B was treated with Azacitidine alone.Immune indicators,inflammatory factors,tumor markers,and adverse reactions were compared between the two groups.Results:The levels of CD3+,CD4+,and CD8+in Group A were higher than those in Group B(P<0.05).The tumor necrosis factor-α(TNF-α)level in Group A was lower than that in Group B,while the interferon-γ(IFN-γ)level was higher(P<0.05).The levels of cyclooxygenase-2(COX-2),lactate dehydrogenase(LDH),and vascular endothelial growth factor(VEGF)in Group A were lower than those in Group B(P<0.05).The adverse reaction rate in Group A was lower than that in Group B(P<0.05).Conclusion:The combination of Venetoclax and Azacitidine in the treatment of elderly AML patients can improve immune function,inhibit inflammation,delay disease progression,and is safe and efficient.
文摘Patients with leukemia often suffer from the combined effects of cancer-related fatigue(CRF)and subthreshold depression,which mutually exacerbate each other in a vicious cycle.In this editorial,we comment on the article by Liu et al,published in the World Journal of Psychiatry.We further elucidate the profound impact of subthreshold depressive symptoms on the experience of CRF and complications in patients with leukemia.This editorial highlights the importance of early identification and treatment of subclinical depression,and advocates for a multidisciplinary and integrated treatment approach that includes social support,psychological interventions,and individualized treatment plans.Future research needs to explore the biological mechanisms underlying the interaction between the two to develop more effective prevention and treatment strategies.
基金Hubei Provincial Department of Education Humanities and Social Sciences Youth Project(Project No.:19Q137)Hubei Provincial Department of Education Humanities and Social Sciences Youth Project(Project No.:23Q183)。
文摘Objective:To investigate the efficacy of a tripartite collaborative nursing intervention in enhancing resilience among families of pediatric leukemia patients.Methods:Based on Walsh’s family resilience theory and collaborative nursing principles,and after reviewing a large amount of literature,a tripartite intervention was constructed,which was led by the nursing team,coordinated by medical social workers,and supported by volunteers.Caregivers of pediatric hematology inpatients at a tertiary-level Class A hospital were selected as research subjects.which were divided into a control group(n=30)and an experimental group(n=30)according to a randomized block design.The control group are treated with standard nursing care,which included health education,counseling,and psychological support from nurses.The experimental group,in addition,was provided with a tripartite collaborative nursing intervention for 3 months.Results:The family resilience level,social support,and family function scores of the experimental group were higher than those of the control group,and the differences were statistically significant(P≤0.05).Conclusion:The implementation of tripartite collaborative nursing intervention improves the resilience of families of children suffered from leukemia.
基金supported by grants from the National High Technology Research and Development Program of China(No.2021YFA1101500)the National Natural Science Foundation of China(No.81873427 and No.82070217)the Research and Innovation Team Project for Scientific Breakthroughs at Shanxi Bethune Hospital(No.2024ZHANCHI12)。
文摘The clinical efficacy of immunotherapy in acute myeloid leukemia(AML)remains significantly limited by early relapse and treatment-associated toxicities.This review examines recent advances in antibody-and cell-based immunotherapies for AML,focusing on established targets(CD33,CD123,and CLL1)as well as emerging targets(including CD7,CD70,CD38,and FLT3).Therapeutic modalities discussed include immunoconjugates,bispecific T-cell engagers and chimeric antigen receptor T(CAR-T)cells.Furthermore,we summarize the current challenges impeding the success of immunotherapy in AML and propose strategies to enhance its efficacy.These include combination therapies,structural optimization of CAR constructs,functional enhancement of CAR-T cells,identification of novel targets,and the development of next-generation cellular therapies.Collectively,these approaches aim to offer new insights for improving immunotherapeutic outcomes in AML.
基金Supported by National Natural Science Foundation of China,No.82100625Zhejiang Provincial natural Science Foundation of China,No.Q20H030013.
文摘BACKGROUND The introduction of pegaspargase has greatly advanced the treatment of acute lymphoblastic leukemia(ALL).In the literature,only one case of pegaspargaseinduced multiple organ failure has been reported,and the patient died due to multiple organ failure.CASE SUMMARY Herein,we present a rare case of a 40-year-old man with ALL who developed multiple organ failure after treatment with pegaspargase.The patient had two rare phenomena reflecting poor prognosis,including the discrepancy between clinical manifestations and liver function and persistently low alpha-fetoprotein(AFP)levels from subacute liver failure.However,the patient was successfully treated using a multidisciplinary team approach.CONCLUSION This is the first case report of successful treatment of pegaspargase-induced multiple organ failure.The findings emphasize the importance of a multidisciplinary team approach in treating pegaspargase-induced multiple organ failure.
文摘BACKGROUND The prognosis for acute myeloid leukemia(AML)remains poor,underscoring the need for a deeper understanding of its underlying molecular mechanisms.AIM To assess the significance of SOX11 gene expression in the clinical features,response to treatment,and survival outcomes of adult patients with AML.METHODS This retrospective study enrolled 102 adults with AML.SOX11 gene expression in bone marrow samples was measured using real-time PCR.Data were correlated to the patients’clinical features,response to treatment,and survival rates.RESULTS Increased SOX11 expression was significantly associated with the presence of the FLT3-ITD mutation(P<0.001),the FAB-M2 subtype(P=0.008),and cytogenetic abnormalities(P=0.011).However,no significant association was found between SOX11 expression and other clinical laboratory parameters,complete remission,disease-free survival,or overall survival.CONCLUSION SOX11 expression may serve as a marker to identify specific subsets of AML patients who could benefit from intensive targeted chemotherapy.
文摘BACKGROUND Acute myeloid leukemia(AML)is a complicated disease with uncontrolled hematopoietic precursor proliferation induced by various genetic alterations.Runt-related transcription factor-1(RUNX1)is commonly disrupted by chromosomal translocations in hematological malignancies.AIM To characterize RUNX1 gene rearrangements and copy number variations in newly diagnosed adult AML patients,with an emphasis on the impact of clinical and laboratory features on the outcome.METHODS Fluorescence in situ hybridization was used to test RUNX1 gene alterations in 77 newly diagnosed adult AML cases.NPM1,FLT3/ITD,FLT3/TKD,and KIT mutations were tested by PCR.Prognostic clinical and laboratory findings were studied in relation to RUNX1 alterations.RESULTS RUNX1 abnormalities were detected by fluorescence in situ hybridization in 41.6%of patients:20.8%had translocations,22.1%had amplification,and 5.2%had deletion.Translocations prevailed in AML-M2(P=0.019)with a positive expression of myeloperoxidase(P=0.031),whereas deletions dominated in M4 and M5 subtypes(P=0.008)with a positive association with CD64 expression(P=0.05).The modal chromosomal number was higher in cases having amplifications(P=0.007)and lower in those with deletions(P=0.008).RUNX1 abnormalities were associated with complex karyotypes(P<0.001)and were mutually exclusive of NPM1 mutations.After 44 months of follow-up,RUNX1 abnormalities affected neither patients’response to treatment nor overall survival.CONCLUSION RUNX1 abnormalities were mutually exclusive of NPM1 mutations.RUNX1 abnormalities affected neither patients’response to treatment nor overall survival.
基金National Natural Science Foundation of China (82104246)Postdoctoral Fellowship Program of CPSF (GZB20230996)+2 种基金Natural Science Basic Research Program of Shaanxi (2025JC-YBMS-917)Research Foundation of Air Force Medical University (2024JC054)Xijing Innovation Research Institute Joint Fund Project (LHJJ2023-YX16)。
文摘Myristica is a classic traditional Chinese medicine widely used for leukemia treatment.However,its main active ingredients and underlying mechanisms of action remain poorly understood.In this study,we comprehensively investigated the mechanisms by which Myristica exerted effects on radiation-induced myeloid leukemia(RIML)using molecular docking and network pharmacology.The active ingredients in Myristica were further identified via TCMSP database,potential Myristica-related targets were extracted from GEO,GeneCards,OMIM,and DisGeNET databases,a protein-protein interaction(PPI)network was constructed to screen key targets(followed by GO and KEGG enrichment analyses),and finally the binding affinity between active compounds and key targets was verified.The screening results identified 9 active substances,including Kudos,isoguaiacin,galbacin,and others.Topological analysis of the PPI network revealed that PARP1,ESR1,MTOR,MDM2,HIF1A,and ALB were key targets.GO enrichment analysis showed that these targets were mainly involved in biological processes such as DNA repair,cell cycle regulation,apoptosis,and oxidative stress response.KEGG pathway enrichment analysis indicated that Myristica might exert anti-leukemia effects by regulating signaling pathways such as PI3K-Akt,mTOR,and HIF-1.
文摘Background:Acute Myeloid Leukemia(AML)is a highly aggressive clonal hematological malignancy with limited treatment options.This study aimed to evaluate the therapeutic potential of nigericin,a polyether ionophore derived from Streptomyces DASNCL-29,as a mitochondrial-targeted agent for AML treatment.Methods:Nigericin was isolated from Streptomyces DASNCL-29 and characterized via chromatography and NMR.Its cytotoxicity was tested in MOLM13(sensitive and venetoclax-resistant)and HL60(sensitive and cytarabine-resistant)cells using the MTT assay.Mitochondrial dysfunction was assessed by measuring reactive oxygen species(ROS),mitochondrial membrane potential(Δψm),and mitochondrial mass.Apoptosis was evaluated with Annexin V/PI assays and immunoblotting,while proteomic analysis was conducted using Liquid Chromatography-Tandem Mass Spectrometry(LC-MS/MS)to identify differentially regulated proteins.Results:Nigericin demonstrated potent cytotoxicity with IC50 values of 57.02 nM in MOLM13-sensitive,35.29 nM in MOLM13-resistant,20.49 nM in HL60-sensitive,and 1.197 nM in HL60-cytarabine-resistant cells.Apoptosis was confirmed by Annexin V/PI staining and caspase-3/PARP cleavage,along with MCL-1 downregulation.Mitochondrial dysfunction was evident from increased ROS,reducedΔψm,and decreased mitochondrial mass.Proteomic profiling identified 264 dysregulated proteins,including a 3.8-fold upregulation of Succinate Dehydrogenase[Ubiquinone]Flavoprotein Subunit A(SDHA).Conclusion:Nigericin induces apoptosis in AML cells by disrupting mitochondrial function and enhancing oxidative stress.Its nanomolar potency highlights the need for further mechanistic studies and in vivo evaluations to explore its potential in AML treatment.
文摘Acute lymphoblastic leukemia(ALL)is characterized by overgrowth of immature lymphoid cells in the bone marrow at the expense of normal hematopoiesis.One of the most prioritized tasks is the early and correct diagnosis of this malignancy;however,manual observation of the blood smear is very time-consuming and requires labor and expertise.Transfer learning in deep neural networks is of growing importance to intricate medical tasks such as medical imaging.Our work proposes an application of a novel ensemble architecture that puts together Vision Transformer and EfficientNetV2.This approach fuses deep and spatial features to optimize discriminative power by selecting features accurately,reducing redundancy,and promoting sparsity.Besides the architecture of the ensemble,the advanced feature selection is performed by the Frog-Snake Prey-Predation Relationship Optimization(FSRO)algorithm.FSRO prioritizes the most relevant features while dynamically reducing redundant and noisy data,hence improving the efficiency and accuracy of the classification model.We have compared our method for feature selection against state-of-the-art techniques and recorded an accuracy of 94.88%,a recall of 94.38%,a precision of 96.18%,and an F1-score of 95.63%.These figures are therefore better than the classical methods for deep learning.Though our dataset,collected from four different hospitals,is non-standard and heterogeneous,making the analysis more challenging,although computationally expensive,our approach proves diagnostically superior in cancer detection.Source codes and datasets are available on GitHub.
