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简介：AbstractOxidative stress is caused by the imbalance between the generation of free radicals/reactive oxygen species (ROS) and the antioxidant defense systems, which can activate various transcription factors and affect their transcriptional pathways. Oxidative stress plays an important role in the occurrence and development of leukemia and is closely related to the treatment and prognosis of leukemia. The standard chemotherapy strategies for the pre-treatment of leukemia have many drawbacks. Hence, the usage of antioxidants and oxidants in the treatment of leukemia is being explored and has been preliminarily applied. This article reviews the research progress of oxidative stress and leukemia. In addition, the application of antioxidants treatment in leukemia has been summarized.

简介：Acutemyeloidleukemia(AML)ischaracterizedbytheaccumulationofcirculatingimmatureblaststhatexhibituncontrolledgrowth,lacktheabilitytoundergonormaldifferentiation,andhavedecreasedsensitivitytoapoptosis.Accumulatingevidenceshowsthebonemarrow(BM)nicheiscriticaltothemaintenanceandretentionofhematopoieticstemcells(HSC),includingleukemiastemcells(LSC),andanincreasingnumberofstudieshavedemonstratedthatcrosstalkbetweenLSCandthestromalcellsassociatedwiththisnichegreatlyinfluencesleukemiainitiation,progression,andresponsetotherapy.Undeniably,stromalcellsintheBMnicheprovideasanctuaryinwhichLSCcanacquireadrug-resistantphenotypeandtherebyevadechemotherapyinduceddeath.YinandYang,theancientChinesephilosophicalconcept,vividlyportraystheintricateanddynamicinteractionsbetweenLSCandtheBMniche.Infact,LSC-inducedmicroenvironmentalreprogrammingcontributessignificantlytoleukemogenesis.Thus,identifyingthecriticalsignalingpathwaysinvolvedintheseinteractionswillcontributetotargetoptimizationandcombinatorialdrugtreatmentstrategiestoovercomeacquireddrugresistanceandpreventrelapsefollowingtherapy.Inthisreview,wedescribesomeofthecriticalsignalingpathwaysmediatingBMniche-LSCinteraction,includingSDF1/CXCL12,Wnt/β-catenin,VCAM/VLA-4/NF-κB,CD44,andhypoxiaasanewly-recognizedphysicaldeterminantofresistance,andoutlinetherapeuticstrategiesforovercomingtheseresistancefactors.

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简介：客观：在glucocorticoid之中调查关系受体(GCR)水平，免疫学的分类和在尖锐成淋巴细胞的白血病(所有)的化疗的临床的功效孩子。方法：静脉的血淋巴细胞的GCR水平被受体radioligand绑定试金与童年在50种情况中测量所有和41个正常孩子。有所有的32个孩子的免疫学的分类被ABCimmunoenzymatic方法分析。结果：在正常孩子的静脉的血淋巴细胞的GCR数字是4651

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简介：Objective:Toobservethelong-termeffectofhomoharringtonine(HHT)onchronicgranulocyticleukemia(CGL)anditspharmacologicalmechanism.Methods:76patientswithnewlydiagnosedearlychronicphaseCGLreceivedtreatmentofmerely1.5mg/m2dailyHHTforinductionremissionandlong-termmaintenancetreatment.TheapoptosisrateofbonemarrowCD34+cellsinducedbyHHTwasassayedwithflowcytometer.Results:86.8%patientsachievedCHR,13.2%patientsPHRand31.8%patientsgotcytogeneticresponseinHHTtreatmentgroup,whichwaslongerthan31(8-54)monthsinhydroxyurea(HU)group(P<0.05).TheeffectofapoptosisinductionHHTwasstrongeronCGL-CPpatientsbonemarrowCD34+cellsthanonnormalpersonbonemarrowCD34+cells.Conclusion:HHTisaveryeffectivedrugforremissioninductionandlong-termmaintenancetreatmentinearlychronicphaseCGLpatients.

简介：白血病是造血的房间开发的混乱并且被一房间增长和区别解开描绘。当常规处理经常有严重不利副作用，对为白血病治疗的新奇战术的发展有紧迫的需要。Tryptanthrin(6,12-dihydro-6,12-dioxoindolo-(2,1-b)-quinazoline)是从药用的靛青植物(Ban-Lan-Gen)的弄干的根孤立的自然地发生的、弱基本的碱。有被报导了各种各样生物并且药理学活动包括抗菌剂，反煽动性，immunomodulatory和反肿瘤效果。然而，它房间糟糕仍然是的myeloid上的调节效果和行动机制理解。在这研究，tryptanthrin被显示在一个剂量依赖者和时间依赖者举止压制鼠科的myeloid白血病WEHI-3BJCS房间的增长。它显著地也在syngeneicBALB/c老鼠在vivo减少了WEHI-3BJCS房间的生长。然而，它没在正常的鼠科的腹巨噬细胞上展出重要直接cytotoxicity。流动cytometric分析在G0/G1阶段显示出对待tryptanthrin的WEHI-3BJCS房间的明显的房间周期拘捕。cyclinD2的表示，D3，Cdk2，在WEHI-3BJCS房间的4和6基因被发现在由RT-PCR测量了的24h下面调整。词法、功能的研究表明tryptanthrin能在WEHI-3BJCS房间导致区别，由vacuolation的增加出现在对待tryptanthrin的房间的细胞的颗粒度和减少NBT活动。一起，我们的调查结果建议tryptanthrin可能由引起房间周期拘捕并且由触发房间区别在鼠科的myelomonocytic白血病WEHI-3BJCS房间上施加它的反肿瘤效果。

简介：AbstractIntroduction:There is a known association between primary mediastinal germ cell tumor (PMGCT) and hematologic malignancy that is not linked to treatment. They are exceptionally rare entities with a low morbidity and a poor prognosis.Case presentation:An 11-year-old boy presented with an anterior mediastinal mass diagnosed as a malignant germ cell tumor on the basis of an excisional biopsy. He was found to have acute myeloid leukemia (AML) two years after the chemotherapy for his germ cell tumor. The clinical course was very aggressive with a survival time of only 1 week after diagnosis of AML associated with PMGCT.Conclusion:AML associated with PMGCT needs to be diagnosed correctly. Relevant examinations should be carried out in patients with PMGCTs during and after chemotherapy, and long-term follow-up is still necessary to reduce the risk of morbidity and mortality.

简介：AbstractAdult T-cell leukemia/lymphoma (ATLL) is an aggressive peripheral T-cell lymphoma caused by the human T lymphotropic virus type-1. The skin is affected in approximately half of ATLL patients, and skin lesions may be the first manifestation of the disease. The skin lesions of ATLL are polymorphous, and depend on the type of skin eruption, which makes it possible for doctors to predict the prognosis of the disease based on the characteristics of skin lesions. In this review article, we describe the clinical manifestations and histopathological patterns of skin lesions in ATLL, focus on its diagnostic and prognostic significance, and also summarize the advances in the treatment of ATLL.

简介：AbstractImportance:Burkitt lymphoma with bone marrow involvement and Burkitt leukemia behave aggressively. Thus far, there are limited data concerning survival and toxicity in Chinese children with Burkitt lymphoma or Burkitt leukemia who have undergone treatment with the non-Hodgkin’s lymphoma Berlin-Frankfurt-Münster-90/95 (NHL-BFM-90/95) protocol.Objective:To analyze outcomes and toxicity in pediatric patients who exhibit Burkitt lymphoma with bone marrow involvement or Burkitt leukemia following treatment with the NHL-BFM-90/95 protocol.Methods:Patients aged <18 years with bone marrow involvement/leukemia who were treated with the NHL-BFM-90/95 protocol, with or without rituximab, in Sun Yat-Sen University Cancer Center from April 2004 to December 2018 were included in this retrospective analysis.Results:Twenty-five patients were eligible. Burkitt lymphoma with bone marrow involvement and Burkitt leukemia were present in 10 and 15 patients, respectively. Central nervous system infiltration was not observed in any patients. All patients underwent chemotherapy involving NHL-BFM-90/95 protocol. Six courses of treatment were administered to each patient (v-AA-BB-CC-AA-BB-CC). The BFM-90/95 plus rituximab protocol was administered to 13 patients. The median follow-up interval was 31.9 months (range, 2.5-158 months). Of the 25 patients, four died: three died of tumor progression and one died of therapy abandonment after relief of tumor lysis syndrome. The estimated 5-year event-free survival and overall survival rates were both 85.8% ± 5.0%.Interpretation:Chinese pediatric patients who exhibit Burkitt lymphoma with bone marrow involvement or Burkitt leukemia can achieve optimal treatment outcomes and exhibit good tolerance when using the NHL-BFM-90/95 protocol.

简介：Acutemyeloidleukemia(AML)isaclonaldisordercharacterizedbytheaccumulationofcomplexgenomicalterationsthatdefinethediseasepathophysiologyandoveralloutcome.RecentadvancesinsequencingtechnologieshavedescribedthemolecularlandscapeofAMLandidentifiedseveralsomaticalterationsthatimpactoverallsurvival.Despitealltheseadvancement,severalchallengesremainintranslatingthisinformationintoeffectivetherapy.HereinwewillreviewthemolecularlandscapeofAMLanddiscusstheimpactofthemostcommonsomaticmutationsondiseasebiologyandoutcome.

简介：AbstractImportance:In low resource countries, there has been scarcity of research on the risk factors associated with neutropenic enterocolitis, a serious complication that commonly develops during treatment of cancer patients.Objective:To identify the pattern of intestinal complications in pediatric leukemia patients treated with intensive chemotherapy, including those with neutropenic enterocolitis; to assess the outcome; and to evaluate the risk factors associated with the mortality in these patients.Methods:During the period from June 2015 to December 2016, a prospective study was carried out on pediatric patients diagnosed with acute leukemia who received induction/or re-induction phases of chemotherapy at South Egypt Cancer Institute. Patients with documented episodes of intestinal complications were included in the study. Recovery or death from an episode of intestinal complication was utilized as the primary outcome measure for the study. Using univariable and multivariable methods, potential risk factors associated with mortality were delineated by logistic regression analysis, both for the entire intestinal complications episodes as a whole and for those episodes of neutropenic enterocolitis only.Results:Out of 88 documented episodes of intestinal complications from 77 patients; 58 episodes were identified as neutropenic enterocolitis from 47 patients. In those patients who were having episodes of neutropenic enterocolitis, the presence of abdominal tenderness (OR 4.529, 95%CI 1.062-19.317, P = 0.041); a longer duration of neutropenia (OR 1.215, 95%CI 1.030-1.434, P = 0.021); and hemodynamic instability (OR 17.023, 95%CI 4.095-70.772, P < 0.001), were found to be independently associated with worse outcome.Interpretation:In Upper Egypt, the use of intensive systemic chemotherapy during the induction phase of acute leukemia was found to be associated with potentially lethal intestinal complications. A high index of clinical suspicion is warranted.

简介：AbstractBackground:TOSO, also named Fas inhibitory molecule 3 (FAIM3), has recently been identified as an immunoglobulin M (IgM) Fc receptor (FcμR). Previous studies have shown that TOSO is specifically over-expressed in chronic lymphocytic leukemia (CLL). However, the functions of TOSO in CLL remain unknown. The B-cell receptor (BCR) signaling pathway has been reported to be constitutively activated in CLL. Here, we aimed to investigate the functions of TOSO in the BCR signaling pathway and the pathogenesis of CLL.Methods:We over-expressed TOSO in B-cell lymphoma cell lines (Granta-519 and Z138) by lentiviral transduction and knocked down TOSO by siRNA in primary CLL cells. The over-expression and knockdown of TOSO were confirmed at the RNA level by polymerase chain reaction and protein level by Western blotting. Co-immunoprecipitation with TOSO antibody followed by liquid chromatography coupled with tandem mass spectrometry (IP/LCMS) was used to identify TOSO interacting proteins. Western blotting was performed to detect the activation status of BCR signaling pathways as well as B-cell lymphoma 2 (BCL-2). Flow cytometry was used to examine the apoptosis of TOSO-over-expressing B lymphoma cell lines and TOSO-down-regulated CLL cells via the staining of Annexin V and 7-AAD. One-way analyses of variance were used for intergroup comparisons, while independent samples t tests were used for two-sample comparisons.Results:From IP/LCMS, we identified spleen tyrosine kinase (SYK) as a crucial candidate of TOSO-interacting protein and confirmed it by co-immunoprecipitation. After stimulation with anti-IgM, TOSO over-expression increased the phosphorylation of SYK, and subsequently activated the BCR signaling pathway, which could be reversed by a SYK inhibitor. TOSO knockdown in primary CLL cells resulted in reduced SYK phosphorylation as well as attenuated BCR signaling pathway. The apoptosis rates of the Granta-519 and Z138 cells expressing TOSO were (8.46 ± 2.90)% and (4.20 ± 1.21)%, respectively, significantly lower than the rates of the control groups, which were (25.20 ± 4.60)% and (19.72 ± 1.10)%, respectively (P < 0.05 for both). The apoptosis rate was reduced after knocking down TOSO in the primary CLL cells. In addition, we also found that TOSO down-regulation in primary cells from CLL patients led to decreased expression of BCL-2 as well as lower apoptosis, and vice versa in the cell line.Conclusions:TOSO might be involved in the pathogenesis of CLL by interacting with SYK, enhancing the BCR signaling pathway, and inducing apoptosis resistance.

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简介：Objective:Correctnutritionalassessmentisessentialforleukemiapatientsafterhematopoieticstemcelltransplantation(HSCT).ThisstudyaimedtoinvestigatethebestnutritionalassessmentmethodforleukemiapatientsafterHSCT,andfindthepossiblenutritionalriskofthepatientsduringthetransplantationprocessinordertointerveneinthepatientswithnutritionalrisksandundernourishedpatientstimely,sothattheentiretransplantationprocesscouldbesuccessfullycompleted.Methods:Aprospectivestudywasperformedin108leukemiapatientsafterHSCT,anddifferentnutritionalassessmentmethods,includingnutritionalriskscreening2002(NRS2002),mininutritionalassessment(MNA),subjectiveglobeassessment(SGA)andmalnutritionaluniversalscreeningtools(MUST),wereused.Theassociationsbetweennutritionalstatusofthesepatientsandnutritionalassessmentmethodswereanalyzed.Results:Atotalof108patientscompletedSGA,and99patientscompletedNRS2002,MNAandMUST.Duringthetreatmentprocess,85.2%ofthepatientslostweight,wherein,50%lostweightgreaterthan5%,and42.6%hadsignificantlyreducedfoodintake.Fornutritionalriskassessment,thepositiveratesofNRS2002,MNAandMUSTwere100%,74.7%and63.6%,respectively.Therewasasignificantdifference(P<0.05)amongthepositiveratesofNRS2002,MNAandMUST.Inundernutritionassessment,thepositiverateofSGA(83.3%)wassignificantlyhigherthanthatofMNA(17.2%)(P<0.05),andtheincidencerateofnutritionalriskamongleukemiapatients≤30yearsoldwasgreaterthanthatofpatients>30yearsold(P<0.05).Conclusions:PatientswithleukemiawereinpoornutritionalstatusduringandafterHSCT.Theleukemiapatients≤30yearsoldhadagreaterincidencerateofnutritionalrisk.Asnutritionalriskscreeningtool,thespecificityofNRS2002isnothigh,butitcanbeusedforevaluatingnutritionaldeficiencies.MNAisagoodnutritionalriskscreeningtool,butnotanadequatetoolfornutritionalassessment.Ifassessmentofundernutritionisneces

简介：AbstractBackground:Compared with human leukocyte antigen (HLA)-matched sibling donor (MSD) transplantation, it remains unclear whether haploidentical donor (HID) transplantation has a superior graft-versus-leukemia (GVL) effect for Philadelphia-negative (Ph-) high-risk B-cell acute lymphoblastic leukemia (B-ALL). This study aimed to compare the GVL effect between HID and MSD transplantation for Ph- high-risk B-ALL.Methods:This study population came from two prospective multicenter trials (NCT01883180, NCT02673008). Immunosuppressant withdrawal and prophylactic or pre-emptive donor lymphocyte infusion (DLI) were administered in patients without active graft-versus-host disease (GVHD) to prevent relapse. All patients with measurable residual disease (MRD) positivity posttransplantation (post-MRD+) or non-remission (NR) pre-transplantation received prophylactic/pre-emptive interventions. The primary endpoint was the incidence of post-MRD+.Results:A total of 335 patients with Ph- high-risk B-ALL were enrolled, including 145 and 190, respectively, in the HID and MSD groups. The 3-year cumulative incidence of post-MRD+ was 27.2% (95% confidence interval [CI]: 20.2%-34.7%) and 42.6% (35.5%-49.6%) in the HID and MSD groups (P = 0.003), respectively. A total of 156 patients received DLI, including 60 (41.4%) and 96 (50.5%), respectively, in the HID and MSD groups (P= 0.096). The 3-year cumulative incidence of relapse was 18.6% (95% CI: 12.7%-25.4%) and 25.9% (19.9%-32.3%; P = 0.116) in the two groups, respectively. The 3-year overall survival (OS) was 67.4% (95% CI: 59.1%-74.4%) and 61.6% (54.2%-68.1%; P = 0.382), leukemia-free survival (LFS) was 63.4% (95% CI: 55.0%-70.7%) and 58.2% (50.8%-64.9%; P= 0.429), and GVHD-free/relapse-free survival (GRFS) was 51.7% (95% CI: 43.3%-59.5%) and 37.8% (30.9%-44.6%; P= 0.041), respectively, in the HID and MSD groups.Conclusion:HID transplantation has a lower incidence of post-MRD+ than MSD transplantation, suggesting that HID transplantation might have a superior GVL effect than MSD transplantation for Ph- high-risk B-ALL patients.Trial registration:ClinicalTrials.gov: NCT01883180, NCT02673008.

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简介：Acutemyeloidleukemia(AML)isageneticallyheterogeneousmyeloidmalignancythatoccursmorecommonlyinadults,andhasanincreasingincidence,mostlikelyduetoincreasingage.PrecisediagnosticclassificationofAMLrequiresclinicalandpathologicinformation,thelatterincludingmorphologic,immunophenotypic,cytogeneticandmoleculargeneticanalysis.RiskstratificationinAMLrequirescytogeneticsevaluationasthemostimportantpredictor,withgeneticmutationsprovidingadditionalnecessaryinformation.AMLwithnormalcytogeneticscomprisesabout40%-50%ofallAML,andhasbeenintensivelyinvestigated.Thecurrentlyused2008WorldHealthOrganizationclassificationofhematopoieticneoplasmshasbeenproposedtobeupdatedin2016,alsotoincludeanupdateontheclassificationofAML,duetothecontinuouslyincreasingapplicationofgenomictechniquesthathaveledtomajoradvancesinourknowledgeofthepathogenesisofAML.ThepurposeofthisreviewistodescribesomeoftheserecentmajoradvancesinthediagnosticclassificationandriskstratificationofAML.

简介：biflavonoidisochamaejasmin主要在StellerachamaejasmeL的根被散布。(Thymelaeaceae)那在繁体中文药(TCM)被使用治疗肿瘤，肺结核，和干癣。此处，isochamaejasmin被发现对Bcl-2家庭蛋白质显示出类似的bioactivity到参考Bcl-2ligand(−)通过3D类似搜索的-gossypol。它有选择地跳了到Bclx有K和Mcl-1>是的i价值1.93±0.13mol·L−1和9.98±0.21mol·L−1,分别地。另外，isochamaejasmin显示出细微生长对有是的IC50价值的HL-60的禁止的活动50.40±1.21mol·L−1和中等生长对有IC50价值的K562细胞的禁止的活动是24.51±1.62mol·L−1。而且，isochamaejasmin由增加在Bcl-2-inducedapoptosis小径包含了的caspase-9，caspase-3，和PARP的劈开的蛋白质的细胞内部的表示层次导致了K562房间的apoptosis。这些结果显示isochamaejasmin由禁止Bcl-2家庭蛋白质的活动在白血病房间导致apoptosis，提供为进一步学习S的内在的反癌症机制的证据。chamaejasmeL。