The structure of the Rb gene in 32 cases of acute lymphoid leukemia (ALL) were studied by Southern blotting using 32P-labeled Rb cDNA 3. 8 kb probe- Structural abnormalities of Rb gene were found in 8 cases of ALL, an...The structure of the Rb gene in 32 cases of acute lymphoid leukemia (ALL) were studied by Southern blotting using 32P-labeled Rb cDNA 3. 8 kb probe- Structural abnormalities of Rb gene were found in 8 cases of ALL, an incidence of 25%. Two novel fragments (3. 1 kb, 2- 3 kb)were observed in 5 of 8 cases. We used five pairs of Rb gene primers of exons 18, 19, 21, 22, 27 and amplified Rb gene from 6 cases of ALL with abnormal Rb gene- Only one case was free from products of exons 18 and 2l. The results seemed to indicate that abnormalities of Rb gene might be closely associated with initiation and/or promotion of ALL.展开更多
Autoinhibitory activity has been discovered in murine T lymphocyte leukemia models derived from 615 mice in our lab. It was designated 615 mice leukemia associated inhibitor (LAI-615) . To further confirm whether LAI ...Autoinhibitory activity has been discovered in murine T lymphocyte leukemia models derived from 615 mice in our lab. It was designated 615 mice leukemia associated inhibitor (LAI-615) . To further confirm whether LAI activity could be found in human leukemia, 6 ALL cases and 2 AML cases were examined. The results showed that 5/6 of ALL and 1/2 of AML cases had detectable LAI activity. The different sensitivities of LAI activity were also found between autologous bone marrow cells and human leukemic cell lines, which indicate that autoinhibitory activity might have individual specificity.展开更多
Severe fever with thrombocytopenia syndrome(SFTS),caused by Dabie bandavirus(DBV),triggers aberrant immune activation and cytokine storms,contributing to poor prognosis;however,its immune dysfunction mechanism remains...Severe fever with thrombocytopenia syndrome(SFTS),caused by Dabie bandavirus(DBV),triggers aberrant immune activation and cytokine storms,contributing to poor prognosis;however,its immune dysfunction mechanism remains unclear.Current management relies on symptomatic treatment and glucocorticoids,but no standardized treatment guidelines exist.This study investigated the mechanisms of abnormal lymphocyte function in acute-phase SFTS and the effects of glucocorticoid treatment on lymphoid cells using single-cell RNA sequencing(scRNA-seq)and bioinformatics analysis.We enrolled three healthy volunteers and 13 patients with acute SFTS and divided them into four groups.ScRNA-seq was performed on peripheral blood mononuclear cells from all 16 participants,capturing transcripts from the 3′ends of mRNA.Bioinformatics analyses were used to profile patient immunological signatures,characterize subpopulation compositions,infer developmental trajectories,and assess lymphoid cell interactions.We obtained 120886 lymphoid cells,which were clustered into 23 functionally heterogeneous subsets.Results showed that patients with severe SFTS exhibited stronger inflammatory and adaptive immune responses.Glucocorticoid treatment suppressed inflammation and the interferon response but also inhibited the production of virus-specific antibodies.These findings suggest that appropriate glucocorticoid administration may alleviate the hyperinflammatory state in severe SFTS during the acute phase,although it is not recommended as a conventional treatment because of its potential to suppress antiviral immunity.This study provides insights into SFTS immunopathology and informs the optimized clinical use of glucocorticoids.展开更多
Background:Chronic inflammation is closely associated with the most common and socially significant prostate conditions,including benign prostatic hyperplasia(BPH),prostate cancer(PCa),and prostatitis syndromes.NIHcat...Background:Chronic inflammation is closely associated with the most common and socially significant prostate conditions,including benign prostatic hyperplasia(BPH),prostate cancer(PCa),and prostatitis syndromes.NIHcategory IV prostatitis(histologic prostatitis,HP)is defined as asymptomatic chronic inflammation of the prostate.The presence of lymphoid follicles,referred to as tertiary lymphoid structures(TLSs),along with benign lympho-epithelial lesions(BLELs),is among the key histological indicators of immune inflammation and can be assessed relatively easily.This study aimed to quantitatively assess TLSs and BLELs,as well as their relationship with the severity of HP.Methods:We investigated TLSs and BLELs in 110 prostatic specimens,including inflammatory and normal tissues,within the context of common prostate pathologies such as BPH and PCa.HP was graded as low-grade(LG)or high-grade(HG)based on the severity of inflammation.Results:TLSs were observed in 51 out of 110 cases(46.4%),while BLELs were identified in 78 cases(70.44%).Both TLSs and BLELs co-occurred in 45 cases(40.9%).Statistical analysis revealed a significant correlation between the presence of TLSs,BLELs(individually or combined),and HG-HP(p<0.001).Conclusions:This study is the first to quantitatively evaluate the immunopathologic patterns in the inflamed human prostate by analyzing the presence and cooccurrence of TLSs and BLELs.Their formation,likely triggered by antigenic stimuli and external factors,indicates a chronic inflammatory microenvironment.The strong association between TLSs,BLELs,and HG-HP underscores their potential role in HP aggressiveness.These findings suggest that TLSs and BLELs may be crucial contributors to the pathophysiology and morphogenesis of NIH-category IV prostatitis.Furthermore,TLS/BLEL formation may represent a hallmark of tissue autoimmunity,reflecting the immune or autoimmune phase of this prostatitis subtype.展开更多
Background Fusion genes play a crucial role in the pathogenesis of acute myeloid leukemia(AML).This study investigated the utility of targeted next-generation sequencing(NGS)of RNA for detecting rare and unknown fusio...Background Fusion genes play a crucial role in the pathogenesis of acute myeloid leukemia(AML).This study investigated the utility of targeted next-generation sequencing(NGS)of RNA for detecting rare and unknown fusion genes in patients with AML.Methods A total of 85 adult AML samples previously identified as fusion gene-negative by multiplex nested reverse transcription-polymerase chain reaction(RT-PCR)were subjected to NGS analysis.Results Fusion genes were detected in 21 of 72(29.2%)patients.Among the 26 primary refractory patients,11(42.3%)exhibited fusion genes,whereas among the 18 relapsed patients,fusion genes were identified in five(27.8%).Notably,lysine methyltransferase 2A(KMT2A)and nucleoporin 98(NUP98)rearrangements were enriched in refractory/relapsed patients.Additionally,recurrent fusion transcripts involving eukaryotic translation initiation factor 4A1(EIF4A1)were identified.The identification of additional fusion genes resulted in an approximate 20.8%(11/53)reclassification of medium-risk karyotypes to the high-risk category,thereby enhancing diagnostic accuracy.Conclusions Targeted NGS may complement conventional methods for identifying novel fusions in refractory/relapsed AML;however,its prognostic value requires validation in prospective controlled trials.展开更多
This study systematically analyzed the primary causes of malnutrition in children with leukemia during chemotherapy,clarified the status of malnutrition and specific nutritional intervention measures,and comprehensive...This study systematically analyzed the primary causes of malnutrition in children with leukemia during chemotherapy,clarified the status of malnutrition and specific nutritional intervention measures,and comprehensively evaluated the research progress.The research indicates a shift from basic supportive care toward precision intervention strategies.Immunonutrition approaches,such as omega-3 fatty acid supplementation and probiotics for gut microbiota modulation,significantly mitigate chemotherapy-related side effects and enhance nutritional status.These targeted novel regimens demonstrate clear clinical advantages.The success of nutritional management depends on a multidisciplinary collaboration mechanism.The organic integration of innovative nutritional protocols with standard treatments from hematology,pediatrics,and nutrition departments significantly optimizes treatment outcomes and long-term quality of life for children with leukemia.This interdisciplinary synergy is reshaping contemporary medical models.展开更多
Background:Childhood leukemia,a malignant proliferative disorder of the hematopoietic system and the most common childhood cancer,poses a significant threat to the lives and health of affected children.For parents,a l...Background:Childhood leukemia,a malignant proliferative disorder of the hematopoietic system and the most common childhood cancer,poses a significant threat to the lives and health of affected children.For parents,a leukemia diagnosis in their child is a profoundly traumatic event.As primary caregivers,they endure immense psychological distress and caregiving stress throughout the prolonged and demanding treatment process,which can adversely affect their own well-being and caregiving capacity.However,the psychological mechanisms,such as the role of mindfulness,linking caregiver stress to parental coping strategies remain underexplored,and evidence-based interventions to support these parents are needed.Methods:In Study 1,we administered a cross-sectional survey to 242 parents of children with leukemia who were hospitalized at the Affiliated Hospital of Qingdao University between January and August 2024.Participants completed measures assessing caregiver burden,mindful attention awareness,and parental coping style.In Study 2,we further evaluated the effects of a Mindfulness-Based Stress Reduction(MBSR)intervention.Results:The results of Study 1 revealed:(1)The caregiving stress significantly and negatively predicted coping style(β=−1.18,95%CI[−2.18,−0.18],p<0.01).(2)Caregiving stress also significantly and negatively predicted mindfulness(β=−1.90,95%CI[−2.43,−1.38],p<0.01).(3)Conversely,mindfulness significantly and positively predicted coping style(β=0.85,95%CI[0.62,1.07],p<0.01).These findings suggest that mindfulness mediates the relationship between caregiver burden and coping style.In Study 2,the experimental group showed a significant decrease in caregiver stress post-intervention(t=2.24,p<0.05),a significant increase in mindfulness(t=−4.61,p<0.001),and a significant improvement in coping style(t=−2.36,p<0.01).No significant changes were observed in the control group.Conclusion:MBSR can effectively enhance mindfulness and promote adaptive coping strategies,while reducing caregiver burden among parents of children with leukemia.展开更多
Background:Tertiary lymphoid structures(TLSs)promote antitumor immunity and predict favorable immunotherapy outcomes in breast cancer.The study aimed to investigate how Tryptophan 2,3-dioxygenase(TDO2)-associated tryp...Background:Tertiary lymphoid structures(TLSs)promote antitumor immunity and predict favorable immunotherapy outcomes in breast cancer.The study aimed to investigate how Tryptophan 2,3-dioxygenase(TDO2)-associated tryptophan metabolism influences TLS maturation and B cell class switching in breast cancer.Methods:Bulk transcriptomic data from The Cancer Genome Atlas-Breast Invasive Carcinoma(TCGA-BRCA,n=1055)were analyzed using Gene Set Variation Analysis(GSVA)-based metabolic scoring,immune deconvolution,and TLS quantification.Single-cell RNA sequencing(scRNA-seq,n=26)and spatial transcriptomics(n=1)were applied to map TDO2 expression and TLS spatial organization.Validation was performed by immunohistochemistry(n=38)and multiplex immunofluorescence(n=12).Results:We identified that elevated tryptophan metabolism was predominantly enriched in the Luminal A subtype and delineates an immune-cold phenotype with less immunogenicity,associated with a distinct immune-dominant cellular microenvironment,particularly enriched in T and plasma cells.High expression of the tryptophan-metabolizing enzyme TDO2 was significantly enriched in TLS-low tumors and negatively correlated with TLS maturation signatures.Functional enrichment revealed suppressed B cell class switching and attenuated C-X-C motif chemokine ligand 9(CXCL9)expression in TLS-deficient tumors.Spatial transcriptomics and hotspot analysis demonstrated an inverse spatial correlation between TDO2 expression and TLS core components.Tumors with high tryptophan metabolism showed decreased cluster of differentiation 20(CD20)^(+)and CXCL9^(+)cell infiltration within TLS zones.Tumors with strong TDO2-kynurenine activity displayed impaired TLS organization and attenuated humoral immunity.Conditional spatial co-occurrence modeling confirmed reduced proximity between tryptophan metabolism hotspots and TLS-related immune features.Conclusion:In conclusion,our findings suggest that TDO2-associated tryptophan metabolism is linked to impaired TLS maturation and suppressed B cell class switching in breast cancer.Targeting the TDO2-kynurenine axis may represent a promising strategy to restore TLS formation and enhance immunotherapy responsiveness in breast cancer.展开更多
Objectives Chronic lymphocytic leukemia(CLL)is characterized by progressive immune dysregulation.Invariant natural killer T(iNKT)cells support immune surveillance,but the clinical relevance of their regulatory subsets...Objectives Chronic lymphocytic leukemia(CLL)is characterized by progressive immune dysregulation.Invariant natural killer T(iNKT)cells support immune surveillance,but the clinical relevance of their regulatory subsets remains unclear.FoxP3+regulatory iNKT cells(iNKTreg)and E4BP4+IL-10+(iNKT10)cells may reflect immunoregulatory changes associated with disease progression.The study aimed to quantify circulating iNKTreg and iNKT10 subsets and monocytic myeloid-derived suppressor cells(M-MDSCs)in treatment-naïve CLL patients and evaluate their associations with disease characteristics and time to first treatment(TTFT).Methods Peripheral blood samples from 60 untreated CLL patients and 20 healthy donors were analyzed by flow cytometry to determine iNKTreg and iNKT10 percentages,as well as indoleamine 2,3-dioxygenase(IDO)-expressing M-MDSCs.Receiver operating characteristic(ROC)curves and Cox proportional hazards models were used to assess prognostic significance.Results iNKTreg and iNKT10 percentages were significantly increased in CLL compared with healthy donors(p=0.002).Elevated iNKTreg frequencies were associated with zeta-chain-associated protein of 70 kD(ZAP-70)positivity(p=0.017),CD38 positivity(p=0.048),and treatment requirement during follow-up(p=0.016).Based on an ROC-derived cut-off of 9.6%(AUC=0.753),patients with iNKTreg≥9.6%had shorter TTFT(hazard ratio[HR]=2.71;95%confidence interval[CI],1.13–6.49;p=0.025),although the association was not retained in multivariate analysis(HR=1.27;95%CI,0.44–3.64;p=0.626).iNKTreg and iNKT10 percentages correlated positively with IDO+M-MDSCs(p=0.035 and p=0.044),but not with arginase-1(ARG1)or inducible nitric oxide synthase(NOS2).Conclusion Elevated iNKTreg levels reflect a more aggressive disease phenotype and associate with shorter TTFT in univariate analysis,supporting their exploration as complementary immunological biomarkers in CLL.Functional studies and validation in larger cohorts are needed to determine their prognostic and biological significance.展开更多
Background:Breakpoint Cluster Region-Abelson(BCR::ABL1)fusion protein is essential in the pathogenesis of chronic myeloid leukemia(CML);however,the chronic-to-blast phase transformation remains elusive.We identified n...Background:Breakpoint Cluster Region-Abelson(BCR::ABL1)fusion protein is essential in the pathogenesis of chronic myeloid leukemia(CML);however,the chronic-to-blast phase transformation remains elusive.We identified novel kinesin light chain 2(KLC2)mutations in CML-myeloid blast phase patients.We aimed to examine the functional role of KLC2 mutations in leukemogenesis.Methods:To evaluate the biological role of KLC2 mutants(MT)in CML cells,we expressed KLC2-MT in different human CML cell lines harboring BCR::ABL1 and performed immunoblot,immunofluorescence,cell proliferation,differentiation,and apoptosis;Tyrosine kinase inhibitor(TKI)-drug activities;and clonogenic assays for in vitro functional analyses.We co-expressed KLC2-MT and BCR::ABL1 in mouse bone marrow cells(BMCs)to evaluate their clonogenic and self-renewal abilities ex vivo.Furthermore,we examined tumorigenic activity and drug efficacy in the K562 xenograft model.Results:KLC2-MT overexpression in BCR::ABL1-positive K562 and KU812 CML cells promoted cell proliferation and clonogenic potential,decreased imatinib sensitivity,and reduced apoptosis.Serial colony replating assays revealed that KLC2-MT and BCR::ABL1 co-expression enhanced the self-renewal ability of mouse BMCs with immature morphology.In the K562 xenograft model,KLC2-MT enhanced tumorigenic potential and diminished imatinib efficacy.Further studies reported that KLC2-MT augmented signal transducer and activator of transcription 3(STAT3)activation and nuclear accumulation in imatinib-treated CML cells.KLC2-WT and KLC2-MT interacted with mothers against decapentaplegic homolog 2(SMAD2);however,the latter impaired transforming growth factor-beta(TGF-β)–mediated SMAD2/3 activation while enhancing STAT3 phosphorylation.Conclusions:This study demonstrates the biological and functional importance of KLC2 mutation in CML cells,potentially enabling the development of better treatment strategies for CML patients carrying KLC2 mutations and providing enhanced understanding of the disease progression.展开更多
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
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
This comprehensive review integrates population-based registries,hospital databases and Global Burden of Disease data to describe the evolving leukemia burden in China from 2000 to 2022.The overall incidence has stabi...This comprehensive review integrates population-based registries,hospital databases and Global Burden of Disease data to describe the evolving leukemia burden in China from 2000 to 2022.The overall incidence has stabilized nationally,but the absolute number of cases continues to increase as the population ages.A bimodal age pattern persists,with acute leukemias clustering in young children and older adults,while chronic forms predominate in mid-to-late life,and males are consistently more affected by all subtypes.Rapid expansion of haploidentical hematopoietic stem cell transplantation has resulted in marked survival gains for both acute myeloid leukemia and acute lymphoblastic leukemia,and its seamless integration with molecularly targeted agents,venetoclax-based regimens and chimeric antigen receptor T-cell therapy has transformed acute leukemias into potentially curable diseases for an expanding proportion of patients.In parallel,universal access to tyrosine kinase inhibitors and standardized molecular monitoring have turned chronic myeloid leukemia into a manageable chronic condition,and survival of patients with chronic lymphocytic leukemia is improving as novel Bruton's tyrosine kinase and BCL-2 inhibitors diffuse into clinical practice.Tobacco,obesity,benzene and radon remain the principal modifiable drivers of leukemogenesis.Strengthening data completeness,widening equitable access to precision therapies and controlling these environmental risks are essential to sustaining the observed continuous improvement in leukemia patient survival and ensuring that ever more Chinese patients achieve a cure or durable disease control in the decades ahead.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
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
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
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
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
Objective： To study the characteristics of immunophenotype in acute lymphoblastic leukemia （ALL） and its clinical significance. Methods： Immunophenotyping was performed on 81 ALL patients by three-color flow cytom...Objective： To study the characteristics of immunophenotype in acute lymphoblastic leukemia （ALL） and its clinical significance. Methods： Immunophenotyping was performed on 81 ALL patients by three-color flow cytometry analysis using CD45/SSC gating, meanwhile the cytogenetic analysis was performed on 45 cases out of 81 ALL patients. Results： （1） CD19 was the most commonly expressed of all B-lineage antigens detected with the positive rate being 100%. In T-ALL, the positive expression rate of CD5 and CD7 was the highest, being 90%. Both B-ALL and T-ALL overlapped in expression of lineage antigens. There was no significant difference in the complete remission rate （CR rate） between T-ALL and B-ALL. （2） The incidence of ALL with rayeloid antigens expression （My＋ALL） was 39.5%. CD13 was most often seen among the myeloid markers. My＋ALL always involved in B-lineage antigens and the CR rate in children and adults was 72.2% and 78.6% respectively. （3） The incidence of HAL was 19.8%. Coexpression of B-lineage and myeloid-assoeiated antigens was the commonest subtype in HAL. The expression of CD34 was commonly seen in HAL patients （81.3%）. The CR rate was low in HAL, 50% for children and 40% for adults. （4） Compared to T-ALL, B-ALL, My＋ALL, and HAL had a higher positive rate of CD34 expression with the difference being significant （P〈0.025）. Conclusion： Immunophenotyping had remarkable predominance in diagnosing special category of ALL （such as HAL and My＋ALL）; CD19 and CD5 were highly sensitive in diagnosing B-ALL and T-ALL, but less special, and overlapping was found in expression. No significant association was found between the expression of CD34 or myeloid antigens and CR rate, while low CR rate was found in HAL patients, especially for those coexpressing CD34 antigen.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
文摘The structure of the Rb gene in 32 cases of acute lymphoid leukemia (ALL) were studied by Southern blotting using 32P-labeled Rb cDNA 3. 8 kb probe- Structural abnormalities of Rb gene were found in 8 cases of ALL, an incidence of 25%. Two novel fragments (3. 1 kb, 2- 3 kb)were observed in 5 of 8 cases. We used five pairs of Rb gene primers of exons 18, 19, 21, 22, 27 and amplified Rb gene from 6 cases of ALL with abnormal Rb gene- Only one case was free from products of exons 18 and 2l. The results seemed to indicate that abnormalities of Rb gene might be closely associated with initiation and/or promotion of ALL.
文摘Autoinhibitory activity has been discovered in murine T lymphocyte leukemia models derived from 615 mice in our lab. It was designated 615 mice leukemia associated inhibitor (LAI-615) . To further confirm whether LAI activity could be found in human leukemia, 6 ALL cases and 2 AML cases were examined. The results showed that 5/6 of ALL and 1/2 of AML cases had detectable LAI activity. The different sensitivities of LAI activity were also found between autologous bone marrow cells and human leukemic cell lines, which indicate that autoinhibitory activity might have individual specificity.
基金supported by the National Natural Science Foundation of China(Grant No.81871242)the"YiQi"Fund Project(Grant Nos.2024YQZL01 and 2023YQFH05)the National Key Research and Development Program of China(Grant No.2022YFF0710100).
文摘Severe fever with thrombocytopenia syndrome(SFTS),caused by Dabie bandavirus(DBV),triggers aberrant immune activation and cytokine storms,contributing to poor prognosis;however,its immune dysfunction mechanism remains unclear.Current management relies on symptomatic treatment and glucocorticoids,but no standardized treatment guidelines exist.This study investigated the mechanisms of abnormal lymphocyte function in acute-phase SFTS and the effects of glucocorticoid treatment on lymphoid cells using single-cell RNA sequencing(scRNA-seq)and bioinformatics analysis.We enrolled three healthy volunteers and 13 patients with acute SFTS and divided them into four groups.ScRNA-seq was performed on peripheral blood mononuclear cells from all 16 participants,capturing transcripts from the 3′ends of mRNA.Bioinformatics analyses were used to profile patient immunological signatures,characterize subpopulation compositions,infer developmental trajectories,and assess lymphoid cell interactions.We obtained 120886 lymphoid cells,which were clustered into 23 functionally heterogeneous subsets.Results showed that patients with severe SFTS exhibited stronger inflammatory and adaptive immune responses.Glucocorticoid treatment suppressed inflammation and the interferon response but also inhibited the production of virus-specific antibodies.These findings suggest that appropriate glucocorticoid administration may alleviate the hyperinflammatory state in severe SFTS during the acute phase,although it is not recommended as a conventional treatment because of its potential to suppress antiviral immunity.This study provides insights into SFTS immunopathology and informs the optimized clinical use of glucocorticoids.
文摘Background:Chronic inflammation is closely associated with the most common and socially significant prostate conditions,including benign prostatic hyperplasia(BPH),prostate cancer(PCa),and prostatitis syndromes.NIHcategory IV prostatitis(histologic prostatitis,HP)is defined as asymptomatic chronic inflammation of the prostate.The presence of lymphoid follicles,referred to as tertiary lymphoid structures(TLSs),along with benign lympho-epithelial lesions(BLELs),is among the key histological indicators of immune inflammation and can be assessed relatively easily.This study aimed to quantitatively assess TLSs and BLELs,as well as their relationship with the severity of HP.Methods:We investigated TLSs and BLELs in 110 prostatic specimens,including inflammatory and normal tissues,within the context of common prostate pathologies such as BPH and PCa.HP was graded as low-grade(LG)or high-grade(HG)based on the severity of inflammation.Results:TLSs were observed in 51 out of 110 cases(46.4%),while BLELs were identified in 78 cases(70.44%).Both TLSs and BLELs co-occurred in 45 cases(40.9%).Statistical analysis revealed a significant correlation between the presence of TLSs,BLELs(individually or combined),and HG-HP(p<0.001).Conclusions:This study is the first to quantitatively evaluate the immunopathologic patterns in the inflamed human prostate by analyzing the presence and cooccurrence of TLSs and BLELs.Their formation,likely triggered by antigenic stimuli and external factors,indicates a chronic inflammatory microenvironment.The strong association between TLSs,BLELs,and HG-HP underscores their potential role in HP aggressiveness.These findings suggest that TLSs and BLELs may be crucial contributors to the pathophysiology and morphogenesis of NIH-category IV prostatitis.Furthermore,TLS/BLEL formation may represent a hallmark of tissue autoimmunity,reflecting the immune or autoimmune phase of this prostatitis subtype.
基金supported by the National Natural Science Foundation of China(No.82100164,82302692)the Capital Medical University Research Cultivation Fund(No.PYZ22099)the Guangdong Provincial Medical Science and Technology Research Fund Project(No.A2024190).
文摘Background Fusion genes play a crucial role in the pathogenesis of acute myeloid leukemia(AML).This study investigated the utility of targeted next-generation sequencing(NGS)of RNA for detecting rare and unknown fusion genes in patients with AML.Methods A total of 85 adult AML samples previously identified as fusion gene-negative by multiplex nested reverse transcription-polymerase chain reaction(RT-PCR)were subjected to NGS analysis.Results Fusion genes were detected in 21 of 72(29.2%)patients.Among the 26 primary refractory patients,11(42.3%)exhibited fusion genes,whereas among the 18 relapsed patients,fusion genes were identified in five(27.8%).Notably,lysine methyltransferase 2A(KMT2A)and nucleoporin 98(NUP98)rearrangements were enriched in refractory/relapsed patients.Additionally,recurrent fusion transcripts involving eukaryotic translation initiation factor 4A1(EIF4A1)were identified.The identification of additional fusion genes resulted in an approximate 20.8%(11/53)reclassification of medium-risk karyotypes to the high-risk category,thereby enhancing diagnostic accuracy.Conclusions Targeted NGS may complement conventional methods for identifying novel fusions in refractory/relapsed AML;however,its prognostic value requires validation in prospective controlled trials.
文摘This study systematically analyzed the primary causes of malnutrition in children with leukemia during chemotherapy,clarified the status of malnutrition and specific nutritional intervention measures,and comprehensively evaluated the research progress.The research indicates a shift from basic supportive care toward precision intervention strategies.Immunonutrition approaches,such as omega-3 fatty acid supplementation and probiotics for gut microbiota modulation,significantly mitigate chemotherapy-related side effects and enhance nutritional status.These targeted novel regimens demonstrate clear clinical advantages.The success of nutritional management depends on a multidisciplinary collaboration mechanism.The organic integration of innovative nutritional protocols with standard treatments from hematology,pediatrics,and nutrition departments significantly optimizes treatment outcomes and long-term quality of life for children with leukemia.This interdisciplinary synergy is reshaping contemporary medical models.
基金approved by the Ethics Review Committee of Northwest Normal University(Approval No.:[2023028]).All participants signed the informed consent in this study.
文摘Background:Childhood leukemia,a malignant proliferative disorder of the hematopoietic system and the most common childhood cancer,poses a significant threat to the lives and health of affected children.For parents,a leukemia diagnosis in their child is a profoundly traumatic event.As primary caregivers,they endure immense psychological distress and caregiving stress throughout the prolonged and demanding treatment process,which can adversely affect their own well-being and caregiving capacity.However,the psychological mechanisms,such as the role of mindfulness,linking caregiver stress to parental coping strategies remain underexplored,and evidence-based interventions to support these parents are needed.Methods:In Study 1,we administered a cross-sectional survey to 242 parents of children with leukemia who were hospitalized at the Affiliated Hospital of Qingdao University between January and August 2024.Participants completed measures assessing caregiver burden,mindful attention awareness,and parental coping style.In Study 2,we further evaluated the effects of a Mindfulness-Based Stress Reduction(MBSR)intervention.Results:The results of Study 1 revealed:(1)The caregiving stress significantly and negatively predicted coping style(β=−1.18,95%CI[−2.18,−0.18],p<0.01).(2)Caregiving stress also significantly and negatively predicted mindfulness(β=−1.90,95%CI[−2.43,−1.38],p<0.01).(3)Conversely,mindfulness significantly and positively predicted coping style(β=0.85,95%CI[0.62,1.07],p<0.01).These findings suggest that mindfulness mediates the relationship between caregiver burden and coping style.In Study 2,the experimental group showed a significant decrease in caregiver stress post-intervention(t=2.24,p<0.05),a significant increase in mindfulness(t=−4.61,p<0.001),and a significant improvement in coping style(t=−2.36,p<0.01).No significant changes were observed in the control group.Conclusion:MBSR can effectively enhance mindfulness and promote adaptive coping strategies,while reducing caregiver burden among parents of children with leukemia.
基金supported by grants from the Beijing Xisike Clinical Oncology Research Foundation(No.Y-Young2024-0138)China Postdoctoral Science Foundation(No.2024M750538)Qingdao Chengyang People’s Hospital Fund Project(No.202510300).
文摘Background:Tertiary lymphoid structures(TLSs)promote antitumor immunity and predict favorable immunotherapy outcomes in breast cancer.The study aimed to investigate how Tryptophan 2,3-dioxygenase(TDO2)-associated tryptophan metabolism influences TLS maturation and B cell class switching in breast cancer.Methods:Bulk transcriptomic data from The Cancer Genome Atlas-Breast Invasive Carcinoma(TCGA-BRCA,n=1055)were analyzed using Gene Set Variation Analysis(GSVA)-based metabolic scoring,immune deconvolution,and TLS quantification.Single-cell RNA sequencing(scRNA-seq,n=26)and spatial transcriptomics(n=1)were applied to map TDO2 expression and TLS spatial organization.Validation was performed by immunohistochemistry(n=38)and multiplex immunofluorescence(n=12).Results:We identified that elevated tryptophan metabolism was predominantly enriched in the Luminal A subtype and delineates an immune-cold phenotype with less immunogenicity,associated with a distinct immune-dominant cellular microenvironment,particularly enriched in T and plasma cells.High expression of the tryptophan-metabolizing enzyme TDO2 was significantly enriched in TLS-low tumors and negatively correlated with TLS maturation signatures.Functional enrichment revealed suppressed B cell class switching and attenuated C-X-C motif chemokine ligand 9(CXCL9)expression in TLS-deficient tumors.Spatial transcriptomics and hotspot analysis demonstrated an inverse spatial correlation between TDO2 expression and TLS core components.Tumors with high tryptophan metabolism showed decreased cluster of differentiation 20(CD20)^(+)and CXCL9^(+)cell infiltration within TLS zones.Tumors with strong TDO2-kynurenine activity displayed impaired TLS organization and attenuated humoral immunity.Conditional spatial co-occurrence modeling confirmed reduced proximity between tryptophan metabolism hotspots and TLS-related immune features.Conclusion:In conclusion,our findings suggest that TDO2-associated tryptophan metabolism is linked to impaired TLS maturation and suppressed B cell class switching in breast cancer.Targeting the TDO2-kynurenine axis may represent a promising strategy to restore TLS formation and enhance immunotherapy responsiveness in breast cancer.
基金funded by the Medical University of Lublin,Poland,grant number DS 458.
文摘Objectives Chronic lymphocytic leukemia(CLL)is characterized by progressive immune dysregulation.Invariant natural killer T(iNKT)cells support immune surveillance,but the clinical relevance of their regulatory subsets remains unclear.FoxP3+regulatory iNKT cells(iNKTreg)and E4BP4+IL-10+(iNKT10)cells may reflect immunoregulatory changes associated with disease progression.The study aimed to quantify circulating iNKTreg and iNKT10 subsets and monocytic myeloid-derived suppressor cells(M-MDSCs)in treatment-naïve CLL patients and evaluate their associations with disease characteristics and time to first treatment(TTFT).Methods Peripheral blood samples from 60 untreated CLL patients and 20 healthy donors were analyzed by flow cytometry to determine iNKTreg and iNKT10 percentages,as well as indoleamine 2,3-dioxygenase(IDO)-expressing M-MDSCs.Receiver operating characteristic(ROC)curves and Cox proportional hazards models were used to assess prognostic significance.Results iNKTreg and iNKT10 percentages were significantly increased in CLL compared with healthy donors(p=0.002).Elevated iNKTreg frequencies were associated with zeta-chain-associated protein of 70 kD(ZAP-70)positivity(p=0.017),CD38 positivity(p=0.048),and treatment requirement during follow-up(p=0.016).Based on an ROC-derived cut-off of 9.6%(AUC=0.753),patients with iNKTreg≥9.6%had shorter TTFT(hazard ratio[HR]=2.71;95%confidence interval[CI],1.13–6.49;p=0.025),although the association was not retained in multivariate analysis(HR=1.27;95%CI,0.44–3.64;p=0.626).iNKTreg and iNKT10 percentages correlated positively with IDO+M-MDSCs(p=0.035 and p=0.044),but not with arginase-1(ARG1)or inducible nitric oxide synthase(NOS2).Conclusion Elevated iNKTreg levels reflect a more aggressive disease phenotype and associate with shorter TTFT in univariate analysis,supporting their exploration as complementary immunological biomarkers in CLL.Functional studies and validation in larger cohorts are needed to determine their prognostic and biological significance.
基金supported by grants from the Ministry of Science and Technology,Taiwan(MOST108-2314-B-182-006,MOST109-2314-B-182-071:Lee-Yung Shih)the Ministry of Health and Welfare,Taiwan(MOHW110-TDU-B-212-134011:Lee-Yung Shih)+3 种基金Chang Gung Memorial Hospital(CMRPG3D1524,OMRPG3E0031:Lee-Yung Shih)the Grant-in-Aid for the Japan Society for the Promotion of Science(JSPS)KAKENHI(JP19H05656:Seishi Ogawa,22K16320:Yotaro Ochi)the Japan Agency for Medical Research and Development(AMED)(JP19cm0106501h0004,JP19ck0106250h0003:Seishi Ogawa)the Ministry of Education,Culture,Sports,Science and Technology of Japan(MEXT)(hp200138,hp210167:Seishi Ogawa)。
文摘Background:Breakpoint Cluster Region-Abelson(BCR::ABL1)fusion protein is essential in the pathogenesis of chronic myeloid leukemia(CML);however,the chronic-to-blast phase transformation remains elusive.We identified novel kinesin light chain 2(KLC2)mutations in CML-myeloid blast phase patients.We aimed to examine the functional role of KLC2 mutations in leukemogenesis.Methods:To evaluate the biological role of KLC2 mutants(MT)in CML cells,we expressed KLC2-MT in different human CML cell lines harboring BCR::ABL1 and performed immunoblot,immunofluorescence,cell proliferation,differentiation,and apoptosis;Tyrosine kinase inhibitor(TKI)-drug activities;and clonogenic assays for in vitro functional analyses.We co-expressed KLC2-MT and BCR::ABL1 in mouse bone marrow cells(BMCs)to evaluate their clonogenic and self-renewal abilities ex vivo.Furthermore,we examined tumorigenic activity and drug efficacy in the K562 xenograft model.Results:KLC2-MT overexpression in BCR::ABL1-positive K562 and KU812 CML cells promoted cell proliferation and clonogenic potential,decreased imatinib sensitivity,and reduced apoptosis.Serial colony replating assays revealed that KLC2-MT and BCR::ABL1 co-expression enhanced the self-renewal ability of mouse BMCs with immature morphology.In the K562 xenograft model,KLC2-MT enhanced tumorigenic potential and diminished imatinib efficacy.Further studies reported that KLC2-MT augmented signal transducer and activator of transcription 3(STAT3)activation and nuclear accumulation in imatinib-treated CML cells.KLC2-WT and KLC2-MT interacted with mothers against decapentaplegic homolog 2(SMAD2);however,the latter impaired transforming growth factor-beta(TGF-β)–mediated SMAD2/3 activation while enhancing STAT3 phosphorylation.Conclusions:This study demonstrates the biological and functional importance of KLC2 mutation in CML cells,potentially enabling the development of better treatment strategies for CML patients carrying KLC2 mutations and providing enhanced understanding of the disease progression.
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 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supported by the National Key Research and Development Program of China(No.2022YFA1103300)the Major Program of the National Natural Science Foundation of China(No.82293630)+3 种基金the Beijing Municipal Science&Technology Commission(No.Z211100002921071)the Peking University Medicine Fund for the World’s Leading Discipline or Discipline Cluster Development(No.71003Y3035)the National Natural Science Foundation of China(No.82570262 and No.82570208)the Beijing Natural Science Foundation(No.L252196)。
文摘This comprehensive review integrates population-based registries,hospital databases and Global Burden of Disease data to describe the evolving leukemia burden in China from 2000 to 2022.The overall incidence has stabilized nationally,but the absolute number of cases continues to increase as the population ages.A bimodal age pattern persists,with acute leukemias clustering in young children and older adults,while chronic forms predominate in mid-to-late life,and males are consistently more affected by all subtypes.Rapid expansion of haploidentical hematopoietic stem cell transplantation has resulted in marked survival gains for both acute myeloid leukemia and acute lymphoblastic leukemia,and its seamless integration with molecularly targeted agents,venetoclax-based regimens and chimeric antigen receptor T-cell therapy has transformed acute leukemias into potentially curable diseases for an expanding proportion of patients.In parallel,universal access to tyrosine kinase inhibitors and standardized molecular monitoring have turned chronic myeloid leukemia into a manageable chronic condition,and survival of patients with chronic lymphocytic leukemia is improving as novel Bruton's tyrosine kinase and BCL-2 inhibitors diffuse into clinical practice.Tobacco,obesity,benzene and radon remain the principal modifiable drivers of leukemogenesis.Strengthening data completeness,widening equitable access to precision therapies and controlling these environmental risks are essential to sustaining the observed continuous improvement in leukemia patient survival and ensuring that ever more Chinese patients achieve a cure or durable disease control in the decades ahead.
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.
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.
文摘Objective： To study the characteristics of immunophenotype in acute lymphoblastic leukemia （ALL） and its clinical significance. Methods： Immunophenotyping was performed on 81 ALL patients by three-color flow cytometry analysis using CD45/SSC gating, meanwhile the cytogenetic analysis was performed on 45 cases out of 81 ALL patients. Results： （1） CD19 was the most commonly expressed of all B-lineage antigens detected with the positive rate being 100%. In T-ALL, the positive expression rate of CD5 and CD7 was the highest, being 90%. Both B-ALL and T-ALL overlapped in expression of lineage antigens. There was no significant difference in the complete remission rate （CR rate） between T-ALL and B-ALL. （2） The incidence of ALL with rayeloid antigens expression （My＋ALL） was 39.5%. CD13 was most often seen among the myeloid markers. My＋ALL always involved in B-lineage antigens and the CR rate in children and adults was 72.2% and 78.6% respectively. （3） The incidence of HAL was 19.8%. Coexpression of B-lineage and myeloid-assoeiated antigens was the commonest subtype in HAL. The expression of CD34 was commonly seen in HAL patients （81.3%）. The CR rate was low in HAL, 50% for children and 40% for adults. （4） Compared to T-ALL, B-ALL, My＋ALL, and HAL had a higher positive rate of CD34 expression with the difference being significant （P〈0.025）. Conclusion： Immunophenotyping had remarkable predominance in diagnosing special category of ALL （such as HAL and My＋ALL）; CD19 and CD5 were highly sensitive in diagnosing B-ALL and T-ALL, but less special, and overlapping was found in expression. No significant association was found between the expression of CD34 or myeloid antigens and CR rate, while low CR rate was found in HAL patients, especially for those coexpressing CD34 antigen.
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.
