Objectives:Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia and Philadelphia-like B-cell acute lymphoblastic leukemia(Ph+/Ph-like ALL)constitute the majority of relapsed/refractory B-ALL(R/R B-ALL)...Objectives:Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia and Philadelphia-like B-cell acute lymphoblastic leukemia(Ph+/Ph-like ALL)constitute the majority of relapsed/refractory B-ALL(R/R B-ALL)cases,highlighting an urgent need to discover new therapeutic targets.This study aims to elucidate the mechanisms underlying poor prognosis in Ph+/Ph-like ALL through transcriptome sequencing and functional cytological assays,with the goal of informing new clinical treatment strategies.Results:Transcriptomic analysis of Ph+/Ph-like ALL patients revealed that low expression of P2X Purinoceptor 1(P2RX1)was associated with unfavorable outcomes.Specifically,patients with poor prognosis and low P2RX1 expression exhibited downregulation of genes involved in energy and calcium metabolism pathways,along with upregulation of genes governing key cellular processes such as cell proliferation(e.g.,MYC),cell cycle progression(e.g.,CCND2),and apoptosis inhibition(e.g.,DASP6).Cellular experiments demonstrated that SUP-B15 cells overexpressing P2RX1 displayed elevated intracellular levels of ATP,calcium,and glucose,together with enhanced glycolytic capacity,compared to empty vector controls.Treatment of SUP-B15 cells with dexamethasone(Dex),Imatinib,or their combination significantly suppressed proliferation and promoted apoptosis,which was accompanied by increases in intracellular ATP,calcium,and glucose.Moreover,exogenous ATP administration(a P2RX1 agonist)enhanced apoptosis and inhibited proliferation in control cells.Conversely,treatment with NF449(a P2RX1 inhibitor)increased proliferation in both P2RX1-overexpressing and control SUP-B15 cells.Conclusion:Our findings indicate that P2RX1 may exert this function through modulating energy metabolism and calcium homeostasis,resulting in elevated intracellular calcium levels.Sustained elevation of calcium promotes apoptosis,whereas exogenous ATP activates P2RX1,enhances calcium influx,and attenuates the suppression of apoptosis associated with P2RX1 underexpression,ultimately correlating with improved treatment response.展开更多
Automatic detection of Leukemia or blood cancer is one of the most challenging tasks that need to be addressed in the healthcare system.Analysis of white blood cells(WBCs)in the blood or bone marrow microscopic slide ...Automatic detection of Leukemia or blood cancer is one of the most challenging tasks that need to be addressed in the healthcare system.Analysis of white blood cells(WBCs)in the blood or bone marrow microscopic slide images play a crucial part in early identification to facilitate medical experts.For Acute Lymphocytic Leukemia(ALL),the most preferred part of the blood or marrow is to be analyzed by the experts before it spreads in the whole body and the condition becomes worse.The researchers have done a lot of work in this field,to demonstrate a comprehensive analysis few literature reviews have been published focusing on various artificial intelligence-based techniques like machine and deep learning detection of ALL.The systematic review has been done in this article under the PRISMA guidelines which presents the most recent advancements in this field.Different image segmentation techniques were broadly studied and categorized from various online databases like Google Scholar,Science Direct,and PubMed as image processing-based,traditional machine and deep learning-based,and advanced deep learning-based models were presented.Convolutional Neural Networks(CNN)based on traditional models and then the recent advancements in CNN used for the classification of ALL into its subtypes.A critical analysis of the existing methods is provided to offer clarity on the current state of the field.Finally,the paper concludes with insights and suggestions for future research,aiming to guide new researchers in the development of advanced automated systems for detecting life-threatening diseases.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 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
Measurable residual disease(MRD)has become a critical biomarker in the management of acute lymphoblastic leukemia(ALL),particularly for patients undergoing allogeneic hematopoietic stem cell transplantation(allo-HSCT)...Measurable residual disease(MRD)has become a critical biomarker in the management of acute lymphoblastic leukemia(ALL),particularly for patients undergoing allogeneic hematopoietic stem cell transplantation(allo-HSCT).The incorporation of MRD-directed strategies into clinical practice can enable personalized therapy and improve outcomes in ALL patients.Growing evidence has demonstrated that MRD status not only reflects the treatment response and relapse risk but also informs clinical decisions across the transplant continuum,including transplant indications,donor selection,conditioning regimens,and post-transplant interventions.With the advent of highly sensitive technologies such as real-time polymerase chain reaction and next-generation sequencing,MRD assessment has reached unprecedented accuracy,enabling precision medicine for ALL.This review systematically addresses six key clinical questions related to the application of MRD in ALL patients undergoing transplantation.We discuss optimal MRD detection methods,timing and sampling strategies,the prognostic implications of MRD positivity or clearance,and MRD-directed approaches before and after allo-HSCT.We further highlight emerging immunotherapeutic options and research gaps that must be addressed to refine MRD-guided strategies.In summary,incorporating MRD evaluation into routine clinical practice has the potential to optimize transplant outcomes and reduce relapse in ALL patients.展开更多
Blinatumomab has demonstrated efficacy in B-cell acute lymphoblastic leukemia(B-ALL),achieving a measurable residual disease(MRD)negativity rate of 78%(1).Its addition to consolidation chemotherapy or administration p...Blinatumomab has demonstrated efficacy in B-cell acute lymphoblastic leukemia(B-ALL),achieving a measurable residual disease(MRD)negativity rate of 78%(1).Its addition to consolidation chemotherapy or administration prior to allogeneic hematopoietic stem cell transplantation(allo-HSCT)has been shown to significantly improve overall survival(OS)and relapse-free survival(RFS)in adult B-ALL patients(2,3).展开更多
Objective To explore the effects of resveratrol-induced apoptosis and autophagy in T-cell acute lymphoblastic leukemia （T-ALL） cells and potential molecular mechanisms. Methods The anti-proliferation effect of resve...Objective To explore the effects of resveratrol-induced apoptosis and autophagy in T-cell acute lymphoblastic leukemia （T-ALL） cells and potential molecular mechanisms. Methods The anti-proliferation effect of resveratrol-induced, apoptosis and autophagy on T-ALL cells were detected by using MTI- test, immunofluorescence, electronic microscope, and flow cytometry, respectively. Western blotting was performed for detecting changes of apoptosis-associated proteins, cell cycle regulatory proteins and state of activation of Akt, mTOR, p70S6K, 4E-BP1, and p38-MAPK. Results Resveratrol inhibited the proliferation and dose and time-dependent manner. It also induced cyclin-dependent kinase （CDK） inhibitors p21 and induced apoptosis and autophagy in T-ALL cells in a cell cycle arrest at G0/G1 phase via up regulating p27 and down regulating cyclin A and cyclin D1. Western blotting revealed that resveratrol significantly decreased the expression of antiapoptotic proteins （Mcl-1 and Bcl-2） and increased the expression of proapoptotic proteins （Bax, Bim, and Bad）, and induced cleaved-caspase-3 in a time-dependent manner. Significant increase in ratio of LC3-11/LC3-1 and Beclin 1 was also detected. Furthermore, resveratrol induced significant dephosphorylation of Akt, mTOR, p70S6K, and 4E-BP1, but enhanced specific phosphorylation of p38-MAPK which could be blocked by SB203580. When autophagy was suppressed by 3-MA, apoptosis in T-ALL cells induced by resveratrol was enhanced. Conclusion Our findings have suggested that resveratrol induces cell cycle arrest, apoptosis, and autophagy in T-ALL cells through inhibiting Akt/mTOR/p7OS6K/4E-BP1 and activating p38-MAPK signaling pathways. Autophagy might play a role as a self-defense mechanism in T-ALL cells treated by resveratrol. Therefore, the reasonable inhibition of autophagy in T-ALL cells may serve as a promising strategy for resveratrol induced apoptosis and can be used as adjuvant chemotherapy for T-ALL.展开更多
Objective:The study evaluated the effectiveness of autologous hematopoietic stem cell transplantation(AHSCT)in the treatment of lymphoblastic lymphoma(LL).Methods:We relxospectively analyzed the data from 41 patients ...Objective:The study evaluated the effectiveness of autologous hematopoietic stem cell transplantation(AHSCT)in the treatment of lymphoblastic lymphoma(LL).Methods:We relxospectively analyzed the data from 41 patients with chemotherapy-sensitive LL who underwent hematopoietic stem cell transplantation(HSCT)from December 1989 to December 2009 in a single institution.Results:HSCT was conducted as first-line consolidation therapy and salvage therapy in 36 and 5 patients,respectively.The median follow-up was 97.1 months(range,24.6-173.1 months).The 5-year overall survival(OS)and event-free survival(EFS)rate were 64%and 47%for the initially treated patients,respectively,and were both 20%for the relapsed ones.Bone marrow(BM)involvement and chemotherapy cycles prior to transplantation were identified as significant prognostic factors for EFS in multivariate analysis.Conclusions These results confirm that AHSCT is a reasonable option for chemotherapy-sensitive LL patients in first complete remission(CR1).展开更多
Leukemia relapse is still the leading cause of treatment failure after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for B cell acute lymphoblastic leukemia (B-ALL). Relapsed patients with BALL after ...Leukemia relapse is still the leading cause of treatment failure after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for B cell acute lymphoblastic leukemia (B-ALL). Relapsed patients with BALL after allo-HSCT have a very short median survival. Minimal residual disease (MRD) is predictive of forthcoming hematological relapse after hematopoietic stem cell transplantation (HSCT);furthermore, eliminating MRD effectively prevents relapse. Donor lymphoblastic infusion (DLI) is the main established approach to treat B-ALL with MRD after allo-HSCT. However, about one-third of patients with MRD are non-responsive to DLI and their prognosis worsens. Although donor-derived cluster of differentiation (CD)19-directed chimeric antigen receptor-modified (CAR) T cells (CART19s) can potentially cure leukemia, the efficiency and safety of infusions with these cells have not yet been investigated in patients with MRD after HSCT. Between September 2014 and February 2018, six patients each received one or more infusions of CART19s from HSCT donors. Five (83.33%) achieved MRD-negative remission, and one case was not responsive to the administration of CAR T cells. Three of the six patients are currently alive without leukemia. No patient developed acute graft-versus-host disease (aGVHD), and no patient died of cytokine release syndrome. Donor-derived CAR T cell infusions seem to be an effective and safe intervention for patients with MRD in B-ALL after allo-HSCT and for those who were not responsive to DLI.展开更多
Relapse after allogeneic hematopoietic stem cell transplantation（allo-HSCT） remains a main question on treatment failure. Current strategies for management that usually include salvage chemotherapy, donor lymphocyti...Relapse after allogeneic hematopoietic stem cell transplantation（allo-HSCT） remains a main question on treatment failure. Current strategies for management that usually include salvage chemotherapy, donor lymphocytic infusion and second transplantation. Our study assessed the efficacy of decitabine（DAC） for treating patients with acute lymphoblastic leukemia（ALL） who relapsed after allogeneic hematopoietic stem cell transplantation（allo-HSCT）. We retrospectively analyzed the outcomes of 12 patients with relapsed ALL after allo-HSCT who received DAC therapy. Nine patients received DAC combined with chemotherapy and donor stem cell infusion, and 3 patients received single-agent DAC. Ten of the 12 patients achieved complete remission（CR）, 1 achieved a partial remission（PR）, and 1 had no response（NR） after treatment at the latest follow-up（LFU）, the median survival was 11.2 months（range, 3.8–34, 7 months）. The 1-and 2-year overall survival（OS） rates were 50%（6/12） and 25%（3/12）, respectively. Five patients were still alive; 4 had maintained CR and 1 was alive with disease. Patients with Philadelphia chromosome-positive ALL had higher survival rate than patients with Philadelphia chromosome-negative ALL（57.1% vs. 20%）. No aggravated flares of graft-versus-host disease（GVHD） were observed during DAC treatment. Therefore, DAC may be a promising therapeutic agent for ALL recurrence after allo-HSCT.展开更多
Immunophenotype is critical for diagnosing common B-cell acute lymphoblastic leukemia (common ALL) and detecting minimal residual disease. We developed a protocol to explore the immunophenotypic profiles of common ALL...Immunophenotype is critical for diagnosing common B-cell acute lymphoblastic leukemia (common ALL) and detecting minimal residual disease. We developed a protocol to explore the immunophenotypic profiles of common ALL based on the expression levels of the antigens associated with B lymphoid development, including IL-7Rα (CD127), cytoplasmic CD79a (cCD79a), CD19, VpreB (CD179a), and sIgM, which are successive and essential for progression of B cells along their developmental pathway. Analysis of the immunophenotypes of 48 common ALL cases showed that the immunophenotypic patterns were highly heterogeneous, with the leukemic cell population differing from case to case. Through the comprehensive analysis of immunophenotypic patterns, the profiles of patient-specific composite leukemia cell populations could provide detailed information helpful for the diagnosis, therapeutic monitoring, and individualized therapies for common ALL.展开更多
Objective To explore the role of glucocorticoid （GC） receptor （GR） in rapamycin＇s reversion of GC resistance in humanGC-resistant T-acute lymphoblastic leukemia （ALL） CEM-C1 cells. Methods CEM-C1 cells were cul...Objective To explore the role of glucocorticoid （GC） receptor （GR） in rapamycin＇s reversion of GC resistance in humanGC-resistant T-acute lymphoblastic leukemia （ALL） CEM-C1 cells. Methods CEM-C1 cells were cultured in vitro and treated with rapamycin at different concentrations with or without 1 μmol/L dexamethasone （Dex）. 3-（4, 5-dimethylthiazol-2-yl）-2, 5-diphenyltetrazolium bromide （MTT） test was performed to assess cell proliferation. The cell cycle and cell apoptosis were analyzed by flow cytometry. The expression of GRα mRNA was determined by real-time quantitative RT-PCR. The expression of GR, p-70S6K, Mcl-1, and Bim proteins was detected by Western blot. Results When incubated with rapamycin at different concentrations, CEM-C1 cells showed significant growth inhibition in a time- and concentration-dependent manner. The growth inhibition was synergistically increased when CEM-C1 cells were treated with rapamycin plus 1 μmol/L Dex. CEM-C1 cells treated with rapamycin alone showed no apparent apoptosis, and were arrested at G0/G1 phase. After the treatment with Dex plus rapamycin, CEM-C1 cells demonstrated apparent apoptosis and increased the cell cycle arrested at G0/G1 phase. Rapamycin combined with Dex up-regulated GRα, phosphorylated GR（p-GR）, and pro-apoptotic protein Bim-EL in CEM-C1 cells, but inhibited the expression of p-p70S6K, a downstream target protein ofmTOR （mammalian target of rapamycin）. Conclusion After the treatment with rapamycin plus Dex, Dex resistant CEM-C1 cells induce growth inhibition and apoptosis. The underlying mechanism may involve inhibition of the mTOR signaling pathway and also be associated with up-regulation of GR expression and activation of GC-GR signaling pathway.展开更多
基金supported by Guangdong Province Basic and Applied Basic Research Fund Project(2023A1515220104)Open Fund of Key Laboratory of Hepatoaplenic Surgery,Ministry of Education(Award Number:GPKF202407).
文摘Objectives:Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia and Philadelphia-like B-cell acute lymphoblastic leukemia(Ph+/Ph-like ALL)constitute the majority of relapsed/refractory B-ALL(R/R B-ALL)cases,highlighting an urgent need to discover new therapeutic targets.This study aims to elucidate the mechanisms underlying poor prognosis in Ph+/Ph-like ALL through transcriptome sequencing and functional cytological assays,with the goal of informing new clinical treatment strategies.Results:Transcriptomic analysis of Ph+/Ph-like ALL patients revealed that low expression of P2X Purinoceptor 1(P2RX1)was associated with unfavorable outcomes.Specifically,patients with poor prognosis and low P2RX1 expression exhibited downregulation of genes involved in energy and calcium metabolism pathways,along with upregulation of genes governing key cellular processes such as cell proliferation(e.g.,MYC),cell cycle progression(e.g.,CCND2),and apoptosis inhibition(e.g.,DASP6).Cellular experiments demonstrated that SUP-B15 cells overexpressing P2RX1 displayed elevated intracellular levels of ATP,calcium,and glucose,together with enhanced glycolytic capacity,compared to empty vector controls.Treatment of SUP-B15 cells with dexamethasone(Dex),Imatinib,or their combination significantly suppressed proliferation and promoted apoptosis,which was accompanied by increases in intracellular ATP,calcium,and glucose.Moreover,exogenous ATP administration(a P2RX1 agonist)enhanced apoptosis and inhibited proliferation in control cells.Conversely,treatment with NF449(a P2RX1 inhibitor)increased proliferation in both P2RX1-overexpressing and control SUP-B15 cells.Conclusion:Our findings indicate that P2RX1 may exert this function through modulating energy metabolism and calcium homeostasis,resulting in elevated intracellular calcium levels.Sustained elevation of calcium promotes apoptosis,whereas exogenous ATP activates P2RX1,enhances calcium influx,and attenuates the suppression of apoptosis associated with P2RX1 underexpression,ultimately correlating with improved treatment response.
基金supported by Institute of Information&Communications Technology Planning&Evaluation(IITP)grant funded by the Korea government(MSIT)(RS-2024-00460621,Developing BCI-Based Digital Health Technologies for Mental Illness and Pain Management).
文摘Automatic detection of Leukemia or blood cancer is one of the most challenging tasks that need to be addressed in the healthcare system.Analysis of white blood cells(WBCs)in the blood or bone marrow microscopic slide images play a crucial part in early identification to facilitate medical experts.For Acute Lymphocytic Leukemia(ALL),the most preferred part of the blood or marrow is to be analyzed by the experts before it spreads in the whole body and the condition becomes worse.The researchers have done a lot of work in this field,to demonstrate a comprehensive analysis few literature reviews have been published focusing on various artificial intelligence-based techniques like machine and deep learning detection of ALL.The systematic review has been done in this article under the PRISMA guidelines which presents the most recent advancements in this field.Different image segmentation techniques were broadly studied and categorized from various online databases like Google Scholar,Science Direct,and PubMed as image processing-based,traditional machine and deep learning-based,and advanced deep learning-based models were presented.Convolutional Neural Networks(CNN)based on traditional models and then the recent advancements in CNN used for the classification of ALL into its subtypes.A critical analysis of the existing methods is provided to offer clarity on the current state of the field.Finally,the paper concludes with insights and suggestions for future research,aiming to guide new researchers in the development of advanced automated systems for detecting life-threatening diseases.
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 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.
基金partly supported by grants from the Beijing Municipal Science and Technology Commission(No.Z221100007422008)the National Natural Science Foundation of China(No.82293630 and 82293633)。
文摘Measurable residual disease(MRD)has become a critical biomarker in the management of acute lymphoblastic leukemia(ALL),particularly for patients undergoing allogeneic hematopoietic stem cell transplantation(allo-HSCT).The incorporation of MRD-directed strategies into clinical practice can enable personalized therapy and improve outcomes in ALL patients.Growing evidence has demonstrated that MRD status not only reflects the treatment response and relapse risk but also informs clinical decisions across the transplant continuum,including transplant indications,donor selection,conditioning regimens,and post-transplant interventions.With the advent of highly sensitive technologies such as real-time polymerase chain reaction and next-generation sequencing,MRD assessment has reached unprecedented accuracy,enabling precision medicine for ALL.This review systematically addresses six key clinical questions related to the application of MRD in ALL patients undergoing transplantation.We discuss optimal MRD detection methods,timing and sampling strategies,the prognostic implications of MRD positivity or clearance,and MRD-directed approaches before and after allo-HSCT.We further highlight emerging immunotherapeutic options and research gaps that must be addressed to refine MRD-guided strategies.In summary,incorporating MRD evaluation into routine clinical practice has the potential to optimize transplant outcomes and reduce relapse in ALL patients.
基金supported by the National Natural Science Foundation of China(No.82170206 and No.82470213)Project of Disciplines of Excellence(No.20234Z0002)。
文摘Blinatumomab has demonstrated efficacy in B-cell acute lymphoblastic leukemia(B-ALL),achieving a measurable residual disease(MRD)negativity rate of 78%(1).Its addition to consolidation chemotherapy or administration prior to allogeneic hematopoietic stem cell transplantation(allo-HSCT)has been shown to significantly improve overall survival(OS)and relapse-free survival(RFS)in adult B-ALL patients(2,3).
基金supported by grants from the Department of Science and Technology of Sichuan Province,China (No.2008JY0029-1 and No.07FG002-024)research funds from the Program for Changjiang Scholars and Innovative-Research Team in University (No.IRT0935)
文摘Objective To explore the effects of resveratrol-induced apoptosis and autophagy in T-cell acute lymphoblastic leukemia （T-ALL） cells and potential molecular mechanisms. Methods The anti-proliferation effect of resveratrol-induced, apoptosis and autophagy on T-ALL cells were detected by using MTI- test, immunofluorescence, electronic microscope, and flow cytometry, respectively. Western blotting was performed for detecting changes of apoptosis-associated proteins, cell cycle regulatory proteins and state of activation of Akt, mTOR, p70S6K, 4E-BP1, and p38-MAPK. Results Resveratrol inhibited the proliferation and dose and time-dependent manner. It also induced cyclin-dependent kinase （CDK） inhibitors p21 and induced apoptosis and autophagy in T-ALL cells in a cell cycle arrest at G0/G1 phase via up regulating p27 and down regulating cyclin A and cyclin D1. Western blotting revealed that resveratrol significantly decreased the expression of antiapoptotic proteins （Mcl-1 and Bcl-2） and increased the expression of proapoptotic proteins （Bax, Bim, and Bad）, and induced cleaved-caspase-3 in a time-dependent manner. Significant increase in ratio of LC3-11/LC3-1 and Beclin 1 was also detected. Furthermore, resveratrol induced significant dephosphorylation of Akt, mTOR, p70S6K, and 4E-BP1, but enhanced specific phosphorylation of p38-MAPK which could be blocked by SB203580. When autophagy was suppressed by 3-MA, apoptosis in T-ALL cells induced by resveratrol was enhanced. Conclusion Our findings have suggested that resveratrol induces cell cycle arrest, apoptosis, and autophagy in T-ALL cells through inhibiting Akt/mTOR/p7OS6K/4E-BP1 and activating p38-MAPK signaling pathways. Autophagy might play a role as a self-defense mechanism in T-ALL cells treated by resveratrol. Therefore, the reasonable inhibition of autophagy in T-ALL cells may serve as a promising strategy for resveratrol induced apoptosis and can be used as adjuvant chemotherapy for T-ALL.
基金supported in part by grants from the National Technologies ResearchDevelopment Program of China during the 9th Five-Year Plan Period(A20199610396-906-01-12)+1 种基金the Ying Dong Fok Foundation for Young College Teacher(B231996001)Chinese National Major Project for New Drug Innovation(2008ZX09312,2012ZX09303012)
文摘Objective:The study evaluated the effectiveness of autologous hematopoietic stem cell transplantation(AHSCT)in the treatment of lymphoblastic lymphoma(LL).Methods:We relxospectively analyzed the data from 41 patients with chemotherapy-sensitive LL who underwent hematopoietic stem cell transplantation(HSCT)from December 1989 to December 2009 in a single institution.Results:HSCT was conducted as first-line consolidation therapy and salvage therapy in 36 and 5 patients,respectively.The median follow-up was 97.1 months(range,24.6-173.1 months).The 5-year overall survival(OS)and event-free survival(EFS)rate were 64%and 47%for the initially treated patients,respectively,and were both 20%for the relapsed ones.Bone marrow(BM)involvement and chemotherapy cycles prior to transplantation were identified as significant prognostic factors for EFS in multivariate analysis.Conclusions These results confirm that AHSCT is a reasonable option for chemotherapy-sensitive LL patients in first complete remission(CR1).
文摘Leukemia relapse is still the leading cause of treatment failure after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for B cell acute lymphoblastic leukemia (B-ALL). Relapsed patients with BALL after allo-HSCT have a very short median survival. Minimal residual disease (MRD) is predictive of forthcoming hematological relapse after hematopoietic stem cell transplantation (HSCT);furthermore, eliminating MRD effectively prevents relapse. Donor lymphoblastic infusion (DLI) is the main established approach to treat B-ALL with MRD after allo-HSCT. However, about one-third of patients with MRD are non-responsive to DLI and their prognosis worsens. Although donor-derived cluster of differentiation (CD)19-directed chimeric antigen receptor-modified (CAR) T cells (CART19s) can potentially cure leukemia, the efficiency and safety of infusions with these cells have not yet been investigated in patients with MRD after HSCT. Between September 2014 and February 2018, six patients each received one or more infusions of CART19s from HSCT donors. Five (83.33%) achieved MRD-negative remission, and one case was not responsive to the administration of CAR T cells. Three of the six patients are currently alive without leukemia. No patient developed acute graft-versus-host disease (aGVHD), and no patient died of cytokine release syndrome. Donor-derived CAR T cell infusions seem to be an effective and safe intervention for patients with MRD in B-ALL after allo-HSCT and for those who were not responsive to DLI.
基金supported by grants from the National Natural Science Foundation of China(No.81300412 and No.81470333)
文摘Relapse after allogeneic hematopoietic stem cell transplantation（allo-HSCT） remains a main question on treatment failure. Current strategies for management that usually include salvage chemotherapy, donor lymphocytic infusion and second transplantation. Our study assessed the efficacy of decitabine（DAC） for treating patients with acute lymphoblastic leukemia（ALL） who relapsed after allogeneic hematopoietic stem cell transplantation（allo-HSCT）. We retrospectively analyzed the outcomes of 12 patients with relapsed ALL after allo-HSCT who received DAC therapy. Nine patients received DAC combined with chemotherapy and donor stem cell infusion, and 3 patients received single-agent DAC. Ten of the 12 patients achieved complete remission（CR）, 1 achieved a partial remission（PR）, and 1 had no response（NR） after treatment at the latest follow-up（LFU）, the median survival was 11.2 months（range, 3.8–34, 7 months）. The 1-and 2-year overall survival（OS） rates were 50%（6/12） and 25%（3/12）, respectively. Five patients were still alive; 4 had maintained CR and 1 was alive with disease. Patients with Philadelphia chromosome-positive ALL had higher survival rate than patients with Philadelphia chromosome-negative ALL（57.1% vs. 20%）. No aggravated flares of graft-versus-host disease（GVHD） were observed during DAC treatment. Therefore, DAC may be a promising therapeutic agent for ALL recurrence after allo-HSCT.
基金supported by grants from the National Basic Research Program of China (No.2007CB947802)the Natural Science Foundation of China to H.X. (No.30771228) and to X.M. (No.30771227)
文摘Immunophenotype is critical for diagnosing common B-cell acute lymphoblastic leukemia (common ALL) and detecting minimal residual disease. We developed a protocol to explore the immunophenotypic profiles of common ALL based on the expression levels of the antigens associated with B lymphoid development, including IL-7Rα (CD127), cytoplasmic CD79a (cCD79a), CD19, VpreB (CD179a), and sIgM, which are successive and essential for progression of B cells along their developmental pathway. Analysis of the immunophenotypes of 48 common ALL cases showed that the immunophenotypic patterns were highly heterogeneous, with the leukemic cell population differing from case to case. Through the comprehensive analysis of immunophenotypic patterns, the profiles of patient-specific composite leukemia cell populations could provide detailed information helpful for the diagnosis, therapeutic monitoring, and individualized therapies for common ALL.
基金supported by the research funds from the University Program for Changjiang Scholars and Innovative Research Team(No.IRT0935)the National Natural Science Fund Project(No.30973237)grants from the Department of Science and Technology of Sichuan Province(No.2008JY0029-1,No.07FG002-024,and No.2010JY0004)
文摘Objective To explore the role of glucocorticoid （GC） receptor （GR） in rapamycin＇s reversion of GC resistance in humanGC-resistant T-acute lymphoblastic leukemia （ALL） CEM-C1 cells. Methods CEM-C1 cells were cultured in vitro and treated with rapamycin at different concentrations with or without 1 μmol/L dexamethasone （Dex）. 3-（4, 5-dimethylthiazol-2-yl）-2, 5-diphenyltetrazolium bromide （MTT） test was performed to assess cell proliferation. The cell cycle and cell apoptosis were analyzed by flow cytometry. The expression of GRα mRNA was determined by real-time quantitative RT-PCR. The expression of GR, p-70S6K, Mcl-1, and Bim proteins was detected by Western blot. Results When incubated with rapamycin at different concentrations, CEM-C1 cells showed significant growth inhibition in a time- and concentration-dependent manner. The growth inhibition was synergistically increased when CEM-C1 cells were treated with rapamycin plus 1 μmol/L Dex. CEM-C1 cells treated with rapamycin alone showed no apparent apoptosis, and were arrested at G0/G1 phase. After the treatment with Dex plus rapamycin, CEM-C1 cells demonstrated apparent apoptosis and increased the cell cycle arrested at G0/G1 phase. Rapamycin combined with Dex up-regulated GRα, phosphorylated GR（p-GR）, and pro-apoptotic protein Bim-EL in CEM-C1 cells, but inhibited the expression of p-p70S6K, a downstream target protein ofmTOR （mammalian target of rapamycin）. Conclusion After the treatment with rapamycin plus Dex, Dex resistant CEM-C1 cells induce growth inhibition and apoptosis. The underlying mechanism may involve inhibition of the mTOR signaling pathway and also be associated with up-regulation of GR expression and activation of GC-GR signaling pathway.
