IFN-β通过STAT1诱导SARI表达抑制AML细胞增殖并促进凋亡

目的:探讨IFN-β诱导SARI表达对急性粒细胞性白血病(AML)细胞增殖、凋亡的作用,并筛选其潜在的调控分子。方法:qPCR、Western blot筛选SARI低表达的AML细胞作为实验细胞株;不同浓度IFN-β干预AML细胞,于不同时间采用qPCR、Western blot检测SARI表达,选取IFN-β作用的适当浓度和时间;采用RNA-Seq转录组测序及KEGG富集分析初步筛选IFN-β诱导AML细胞SARI表达的潜在调控分子;通过相应分子抑制剂联合IFN-β处理AML细胞,MTS法检测细胞增殖,流式细胞术检测细胞凋亡;明确该分子参与IFN-β诱导SARI表达对AML细胞增殖及凋亡的作用。结果:HL60和NB4细胞SARI表达相对较低,选为实验细胞株;1 ng/ml IFN-β作用12 h后AML细胞SARI表达升高且细胞增殖被抑制,凋亡增多;筛选STAT1为IFN-β诱导SARI表达的潜在调控分子;抑制STAT1后,IFN-β对AML细胞SARI表达、增殖抑制、凋亡促进的作用被明显逆转。结论:IFN-β可通过STAT1诱导AML细胞SARI表达,抑制细胞增殖,促进细胞凋亡。

虎杖苷对AML细胞增殖、迁移、侵袭及肿瘤生长的影响

目的探讨虎杖苷(PD)对急性髓系白血病(AML)细胞增殖、迁移、侵袭及肿瘤生长的影响。方法将人AML细胞KG-1分为正常组,低、中、高浓度PD组(10、30、60μmol/L的PD),SQ22536组[环磷酸腺苷(cAMP)抑制剂,100μmol/L],高浓度PD和SQ22536联用组(60μmol/L的PD+100μmol/L的SQ22536),考察PD对细胞活力、凋亡率、侵袭和迁移能力、cAMP水平和上皮-间充质转化(EMT)相关蛋白、蛋白激酶A(PKA)蛋白表达的影响。以BALB/c裸鼠为对象,通过皮下接种KG-1细胞悬液建立AML裸鼠移植瘤模型,并分为对照组、PD组、SQ22536组、PD+SQ22536组(每组6只),考察PD对其瘤体体积及质量的影响。结果与正常组细胞或对照组裸鼠比较,PD各浓度组的细胞活力、迁移细胞数、侵袭细胞数和波形蛋白、锌指转录因子Snail蛋白的相对表达量,以及PD组裸鼠的瘤体体积及质量均显著降低,而细胞凋亡率、cAMP水平、PKA和上皮钙黏素的相对表达量均显著升高,且呈浓度依赖性(P<0.05);SQ22536对细胞和裸鼠的作用效果与PD相反,并可显著逆转PD的抗肿瘤活性(P<0.05)。结论PD可能通过激活cAMP/PKA信号通路来抑制AML细胞的增殖、迁移、侵袭,诱导细胞凋亡,抑制EMT进程及肿瘤生长,从而发挥抗AML作用。

AML化疗期间不同时间点流式细胞术MRD检测对预后的影响

目的:探讨AML化疗期间不同时间点流式细胞术微小残留病(MRD)检测对预后的影响。方法:回顾性分析2018年3月到2022年3月确诊并规范化疗的130例成人原发AML患者,用流式细胞术检测MRD,Kaplan-Meier曲线进行生存分析,log-rank检验进行差异性分析,Cox比例风险回归模型进行影响患者生存的单因素和多因素分析。竞争风险模型进行影响患者累计复发率(CIR)的分析,Fine-Gray进行差异性分析。结果:130例患者中,CR181例,CR226例,PR 14例,NR 9例。CR1组OS高于CR2、PR、NR组。CR2组OS高于PR组,但与NR组比较无统计学差异;PR组OS与NR组比较无统计学差异。CR1和CR2的107例患者根据流式细胞术检测的MRD分组,第一次诱导化疗后MRD~-和MRD~+组患者的4年预期RFS率分别为65.3%和27.9%,4年预期OS率分别为58.7%和41.4%,4年预计CIR率分别为34.7%和69.7%,2组比较差异均有统计学意义(χ^(2)=6.639,P=0.010;χ^(2)=6.131,P=0.013;χ^(2)=6.637,P=0.010);第二次化疗后MRD~-和MRD~+组患者的4年预期RFS率分别为50.8%和37.9%,4年预期OS率分别为49.2%和44.5%,4年预计CIR率分别为49.2%和59.5%,2组比较差异均无统计学意义(χ^(2)=1.475,P=0.225;χ^(2)=2.432,P=0.119;χ^(2)=1.416,P=0.234);巩固治疗期间MRD~-和MRD~+组患者的4年预期RFS率分别为51.9%和29.6%,4年预期OS率分别为67.5%和24.6%,4年预计CIR率分别为48.1%和70.4%,2组比较差异均有统计学意义(χ^(2)=20.982,P<0.001;χ^(2)=17.794,P<0.001;χ^(2)=19.879,P<0.001);3个时间点MRD均为阴性和任一时间点为阳性患者的4年预期RFS率分别为69.9%和33.3%,4年预期OS率分别为59.1%和44.7%,4年预计CIR率分别为30.1%和65.1%,2组比较差异均有统计学意义(χ^(2)=7.367,P=0.007;χ^(2)=6.042,P=0.014;χ^(2)=7.662,P=0.006)。单因素分析结果显示,染色体高危核型是影响患者RFS和OS的不利因素,诱导化疗2个疗程达CR、第一次诱导化疗后MRD~-和第二次化疗MRD~-是患者RFS和OS的保护因素;巩固治疗期间MRD~-和3个时间点MRD~-是患者RFS、OS和CIR的保护因素。多因素分析结果显示,诱导化疗2个疗程达CR是患者RFS和CIR的保护因素,巩固治疗期间MRD~-是RFS、OS和CIR的保护因素。结论:成人AML患者早期获得CR和MRD~-,特别是巩固治疗期间的MRD~-是预后良好的标志,流式细胞术是AML患者MRD检测最常用的方法。

地西他滨联合预激方案治疗首程标准诱导化疗未缓解初诊AML患者的效果观察

目的:探讨地西他滨联合预激方案治疗首程标准诱导化疗未缓解初诊急性髓系白血病(AML)患者的疗效及对调节性T淋巴细胞(Treg)相对含量的影响。方法:收集2013年3月-2019年3月陕西省人民医院收治的102例初诊经首程标准诱导化疗未缓解的AML患者(除急性早幼粒细胞白血病)的临床资料进行回顾性分析,根据治疗方案不同对患者进行分组,51例采用预激方案治疗为常规组,51例采用地西他滨联合预激方案治疗为联合组。比较两组疗效、毒副反应发生率、治疗前后生活质量核心量表(QLQ-C30)评分、T淋巴细胞亚群(CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)、Treg)及3年总生存率。结果:联合组治疗总有效率为80.39%,显著高于常规组的62.75%(P<0.05);治疗后联合组QLQ-C30评分为60.27±6.96,较常规组65.73±7.96低(P<0.001);两组毒副反应发生率比较,差异无统计学意义(P>0.05);治疗后联合组CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)水平较常规组高(均P<0.001),而Treg水平较常规组低(P<0.001);联合组3年总生存率为72.55%,高于常规组的52.94%(P<0.001)。结论:地西他滨联合预激方案治疗初诊首程标准诱导化疗未缓解AML患者效果显著,可通过调节Treg相对含量减少抗肿瘤免疫抑制,增强机体免疫功能,从而延长患者生存时间,提高生存质量,且未增加不良反应。

Preferential loss of mismatch repair function in refractory and relapsed acute myeloid leukemia： potential contribution to AML proqression

Acute myeloid leukemia （AML） is an aggressive hematological cancer. Despite therapeutic regimens that lead to complete remission, the vast majority of patients undergo relapse. The molecular mechanisms underlying AML development and relapse remain incompletely defined. To explore whether loss of DNA mismatch repair （MMR） function is involved in AML, we screened two key MMR genes, MSH2 and MLH1, for mutations and promoter hypermethylation in leukemia specimens from 53 AML patients and blood from 17 non-cancer controls. We show here that whereas no amino acid alteration or promoter hypermethylation was detected in all control samples, 18 AML patients exhibited either mutations in MMR genes or hypermethylation in the MLH1 promoter. In vitro functional MMR analysis revealed that almost all the mutations analyzed resulted in loss of MMR function. MMR defects were significantly more frequent in patients with refractory or relapsed AML compared with newly diagnosed patients. These observations suggest for the first time that the loss of MMR function is associated with refractory and relapsed AML and may contribute to disease Datho8enesis.

TEL-AML1融合基因在儿童急性淋巴细胞白血病中的表达及对其疗效及预后的影响

目的探讨TEL-AML1融合基因在儿童急性淋巴细胞白血病中的表达及对其疗效及预后的影响。方法收集儿童急性淋巴细胞白血病106例,应用巢式PCR技术检测TEL-AML1基因表达,根据TEL-AML1基因是否表达,分为TEL/AML1+组、TEL/AML1-组。结果两组患儿年龄、发热率比较,差异有统计学意义(P<0.05),两组患儿其他临床特征比较,差异无统计学意义(P>0.05)。TEL/AML1+组与TEL/AML1-组临床疗效比较,差异具有统计学意义(χ^(2)=7.617,P=0.022)。第12周MRD水平可能为TEL-AML1融合基因阳性儿童急性淋巴细胞白血病患者预后的影响因素(P<0.05)。结论TEL-AML1融合基因阳性儿童急性淋巴细胞白血病患儿生存率更高,第12周MRD水平可能是影响患儿预后因素。

A Newly Developed Serum-free Culture System: Clonal Growth of Human Acute Myelogeneous Leukemia (AML) Progenitors──A Report of 14 AML Cases

A new serum-free culture (SFC) system for human AML-CFU was established and the colony-promoting activity of four recombinant human hematopoietic growth factors (rhHGFs) including granulocyte-macrophage colony-stimulating factor (rhGM-CSF), interleukin-3 (rhIL-3 ),erythropoietin (rhEPO) and newly developed stem cell factor (rhSCF) were investigated in this .SFC system. Under the orthogonal design condition, it was found that human AML-CFU presented optimal clonal growth in an environment of bovine serum albumin (0. 6 %), saturated human transferrin (2×10-5mol/L),cholesterol (2.8 μg/ml) , bovine insulin (15 μg/ml ) . bovine hemin (0. 05 mmol/L), linoleic acid (2.8 μg/ml) , and IMDM. Spontaneously growing colonies were observed in 11 out of 14 cases studied. The plating efficiencies obtained by culturing with rhGM-CSF, rhIL-3, and rhSCF were 0. 776±0. 621 %, 0. 574±0. 510%, and 0. 647±0. 543 %(x±s), respectively. There was one case (M3b) showing no response to all HGFs in both SFC ad SCC. The clonal growth of AML-CFU obtained from peripheral blood of the patient with M6 was unexpectedly marked. As a whole,the newly designed SFC system has been demonstrated to be useful for culture of human AML-CFU from both bone marrow and peripheral blood.

Parametric and Non-Parametric Survival Analysis of Patients with Acute Myeloid Leukemia (AML)

Background: Acute Myeloid leukemia (AML) is the most prominent acute leukemia in adults. In the United States, we experience over 20,000 cases per year. Over the past decade, improvements in the diagnosis of subtypes of AML and advances in therapeutic approaches have improved the outlook for patients with AML. However, despite these advancements, the survival rate among patients who are less than 65 years of age is only 40 percent. Purpose: The purpose of the paper is to study if there exists any significant difference in the survival probabilities of male and female AML patients. Also, we want to investigate if there is any parametric probability distribution that best fits the male and female patient survival and compare the survival probabilities with the non-parametric Kaplan-Meier (KM) method. Methods: We used both parametric and non-parametric statistical methods to perform the survival analysis to assess the survival probabilities of 2015 patients diagnosed with AML. Results: We found evidence of a statistically significant difference between the mean survival time of male and female patients diagnosed with AML. We performed parametric survival analysis and found a Generalized Extreme Value (GEV) distribution best fitting the data of the survival time for male and female patients. We then estimated the survival probabilities and compared them with the frequently used non-parametric Kaplan-Meier (KM) survival method. Conclusion: The comparison between the survival probability estimates of the two methods revealed a better survival probability estimate by the parametric method than the Kaplan-Meier. We also compared the median survival time of male and female patients individually with descriptive, parametric, and non-parametric methods of analysis. The parametric survival analysis is more robust and efficient because it is based on a well-defined parametric probabilistic distribution, hence preferred over the non-parametric Kaplan-Meier estimate. This study offers therapeutic significance for further enhancement to treat patients with Acute Myeloid Leukemia.

Polymorphisms in XRCC5,XRCC6,XRCC7 genes are involved inDNA double-strand breaks(DSBs) repair associated with the risk ofacute myeloid leukemia(AML) in Chinese population

Objective：To investigate the association between the X-ray repair cross complementing（XRCC） group 5, XRCC6 and XRCC7 polymorphisms and risk of acute myeloid leukemia（AML）. Methods：This hospital-based case-control study included 120 AML patients and 210 cancer-free controls in a Chinese population. Three polymorphisms of XRCC5, XRCC6 and XRCC7 were genotyped using the polymerase chain reaction（PCR） or polymerase chain reaction-restriction fragment length polymorphism（PCR-RFLP） method. Results： We found that there was a significant decrease in risk of AML associated with the XRCC6 -61 CG/GG genotype（adjusted odd ratio （OR） = 0.55; 95% confident interval（CI） = 0.34-0.89） compared with the -61CC genotype. For the novel tandem repeat polymorphism （VNTR） in the XRCC5 promoter, we found when the XRCC5 six genotypes were dichotomized（i.e., 2R/2R, 2R/1R versus 2R/0R, 1R/1R, 1R/0R and 0R/0R）, the latter group was associated with increased risk of AML（adjusted OR = 1.67; 95% CI = 1.00-2.79） compared to 2R/ 2R＋2R/1R genotype. However, the XRCC7 6721G〉T polymorphism had no effect on risk of AML. Conclusion：The XRCC6 -61C 〉 G and XRCC5 2R/1R/0R polymorphisms, but not XRCC7 6721G 〉 T polymorphism, could play an important role in the development of AML. Larger scale studies with more detailed data on environment exposure are needed to verify these findings.

Study of Contributing Factors for Cure Response in Patients with Acute Myeloblastic Leukemia （AML）

Leukemia comprises a diverse group of malignancies which is accompanied with genetic disorderliness in hematopoietic cells. We evaluated effective risk factors in recovery process of under treatment patients suffering from acute myeloblastic leukemia （AML）. This study conducted a cross-sectional descriptive-analytical study on a population of 76 samples obtained non-randomly from patients in Taleghani Hospital （Tehran, Iran）. 30.3% patients resulted in death. According to logistic regression results, sexes [OR = 6.40, 95% CI = （0.27, 3.45）], ALT [OR = 1.03, 95% CI = （0.01, 0.05）] and HCT [OR = 0.55, 95% CI = （-1.12, -0.06）] were recognized as significant in prognoses. We predicted the probability of death with an error of 20.03% based on a prognoses system using support vector machine （SVM） classifier. Using this theory, we experienced an error of 20.03%. 46.6% patients with a positive and 20.8% patients without positive drug history resulted in death, which shows a significant correlation between patients＇ drug history and their death.

Impact of comorbid subthreshold depressive symptoms on cancerrelated fatigue and complications in adults with leukemia

BACKGROUND Patients not only experience symptoms caused by cancer but also suffer from the accompanying psychological pain.Therefore,these patients do not have high quality of life.According to the World Health Organization,the incidence of leukemia in China in 2020 was 5.1/100000,the mortality rate was 3.3/100000,and the prevalence rate was 16.7/100000.Therefore,it is important to examine the influence of comorbid subthreshold depressive symptoms on leukemia patients.AIM To determine the impact of comorbid subthreshold depressive symptoms on cancer-related fatigue and complications in leukemia patients,thereby providing a basis for early diagnosis and treatment in clinical practice.METHODS A questionnaire survey was conducted among leukemia patients admitted to a tertiary hospital in Xi'an,Shaanxi Province,China,from August 2022 to December 2023.Patients with a score>16 on the Chinese Classification of Mental Disorders(CCMD-3)and a Hamilton Depression Rating Scale score of 8-17 were classified as the subthreshold depressive group(n=95),while 100 leukemia patients admitted during the same period were classified as the control group.Data were collected using Epidata 3.1 software,and comparisons were made between the two groups regarding general clinical data,the Piper Fatigue Scale(PFS),the Pittsburgh Sleep Quality Index(PSQI),the Numeric Rating Scale for pain assessment,laboratory indicators,and the occurrence of complications.RESULTS In this survey,120 leukemia patients with depression were preliminarily screened,95 patients with subthreshold depression were ultimately selected as the subthreshold depression group,and 100 leukemia patients admitted during the same period were enrolled as the normal group.Comparison of basic clinical data between the two groups revealed no significant differences in age,sex,body mass index,cognitive function,or comorbidity with other chronic diseases.However,there were statistically significant differences in the use of radiotherapy and regular exercise between the two groups(P<0.05).Comparisons of scales and laboratory indicators revealed no significant differences in albumin or PSQI scores between the two groups,but there were statistically significant differences in pain scores,PSQI scores,PFS scores,hemoglobin levels,and C-reactive protein levels(P<0.05).Spearman’s correlation analysis indicated that cancer-related fatigue was correlated with age,hemoglobin levels,C-reactive protein levels,pain,and regular exercise among leukemia patients with subthreshold depression.Multivariate regression analysis revealed that advanced age,combined radiotherapy,pain,and low hemoglobin levels were risk factors for cancer-related fatigue in leukemia patients with comorbid subthreshold depression,while regular exercise was a protective factor against cancer-related fatigue.Follow-up comparisons revealed a significantly lower overall incidence of complications in the control group(4%)than in the depressive group(24.21%;P<0.001).CONCLUSION Leukemia patients with comorbid subthreshold depressive symptoms experience more severe cancer-related fatigue and a higher incidence of complications.These findings may be related to advanced age,combined radiotherapy,pain,and low hemoglobin levels,while regular exercise may effectively alleviate symptoms.

Identification of cell surface markers for acute myeloid leukemia prognosis based on multi-model analysis

Given the extremely high inter-patient heterogeneity of acute myeloid leukemia(AML),the identification of biomarkers for prognostic assessment and therapeutic guidance is critical.Cell surface markers(CSMs)have been shown to play an important role in AML leukemogenesis and progression.In the current study,we evaluated the prognostic potential of all human CSMs in 130 AML patients from The Cancer Genome Atlas(TCGA)based on differential gene expression analysis and univariable Cox proportional hazards regression analysis.By using multi-model analysis,including Adaptive LASSO regression,LASSO regression,and Elastic Net,we constructed a 9-CSMs prognostic model for risk stratification of the AML patients.The predictive value of the 9-CSMs risk score was further validated at the transcriptome and proteome levels.Multivariable Cox regression analysis showed that the risk score was an independent prognostic factor for the AML patients.The AML patients with high 9-CSMs risk scores had a shorter overall and event-free survival time than those with low scores.Notably,single-cell RNA-sequencing analysis indicated that patients with high 9-CSMs risk scores exhibited chemotherapy resistance.Furthermore,PI3K inhibitors were identified as potential treatments for these high-risk patients.In conclusion,we constructed a 9-CSMs prognostic model that served as an independent prognostic factor for the survival of AML patients and held the potential for guiding drug therapy.

儿童t(8;21)/AML1-ETO阳性急性髓系白血病预后相关基因突变的研究进展

近年来儿童急性髓系白血病(acute myeloid leukemia,AML)的发病率逐渐升高,尽管在诊断和治疗方面已取得实质性的进展,但AML的治疗效果仍不及急性淋巴细胞白血病。随着分子生物学技术的不断发展,发现儿童AML不同基因突变对疾病的发生发展起重要作用,影响患儿预后,特别是t(8;21)/AML1-ETO阳性的AML患儿。本文旨在探讨t(8;21)/AML1-ETO阳性AML患儿相关基因突变对预后的影响,以期为临床治疗及预后预测提供依据。

Sunitinib Reduces Acute Myeloid Leukemia Clonogenic Cells in Vitro and Has Potent Inhibitory Effect on Sorted AML ALDH+ Cells

Sunitinib is an orally administered, multi-target tyrosine kinase inhibitor that has been approved by the FDA for the treatment of renal cell carcinoma and imatinib resistant gastro-intestinal tumors. Anti-leukemic activity of sunitinib has been examined in early clinical trials with limited success. However, recent trials on acute myeloid leukemia (AML) patients carrying FLT3 mutations have shown promising results. Effects of sunitinib on leukemic clonogenic cells and potential leukemic stem cells have not been examined so far. We analyzed the anti-proliferative and apoptotic properties of sunitinib on AML-derived cell lines. We also tested the effect of sunitinib on AML patient derived clonogenic cells (AML-CFC), as well as flow-sorted potential leukemic progenitors. Peripheral blood or bone marrow samples were obtained from newly diagnosed AML patients and flow sorted for CD34+ CD133+ or ALDH+ cells. Umbilical cord blood derived CD34+ cells were used as normal controls. Sunitinib induced growth arrest and apoptosis in AML derived cell lines. In addition, 7 μM sunitinib induced 75% reduction of AML-CFC as compared to DMSO treated control (±6.79%;n = 4). In contrast, 7 μM sunitinib treatment of umbilical cord blood derived normal CD34+ cells showed 29% reduction in AML-CFC (±6.77%;n = 5). Treatment of ALDH+ cells sorted from 2 AML cases and CD34+ CD133+ cells from one patient showed reduction of AML-CFC on treatment with sunitinib. Our study highlighted a potent anti-proliferative and proapoptotic effect of sunitinib on AML cell lines, AML patient derived clonogenic cells and potential leukemic stem cells.

RNA splicing and SR protein phosphorylation under stress in acute myeloid leukemia (AML)

SR proteins are essential splicing factors required for constitutive splicing and serving as key regulators of alternative RNA splicing. SR proteins purified from late vaccinia virus infected cells (SR-VV) are hypo-phosphorylated and functionally inactivated as splicing regulatory proteins by a virus-induced partial dephosphorylation, similar to that seen late during an adenovirus infection [Kanopka et al., Nature 393, 185-187, 1998; Huang et al., submitted). In addition, incubating SR-VV or SR-Ad under conditions which restores the phospho-epitopes to the SR proteins regains their activity as splicing represser proteins. Here, we showed that that several genes were up-regulated in at least 50% chemoresistant AML patients, of

长链非编码RNA LINC00987通过细胞色素P450途径促进AML细胞凋亡的机制研究

目的:探讨长链非编码RNA LINC00987在抗肿瘤药物诱导的急性髓系白血病(acute myeloid leukemia,AML)细胞凋亡中的作用及分子机制。方法:通过RT-qPCR检测AML中的LINC00987表达水平。构建稳定敲减LINC00987基因的Molm13细胞(shLINC00987),通过Annexin V/PI检测LINC00987低表达对阿糖胞苷诱导AML细胞凋亡的影响。对LINC00987共表达基因进行信号通路富集,分析LINC00987的表达对细胞色素家族基因的影响。结果:与健康对照组相比,lncRNA LINC00987在AML细胞系和AML病人标本中均显著降低,而在抗AML治疗后缓解组中高表达;此外,低表达LINC00987与AML患者预后不良有关。抗肿瘤药物阿糖胞苷、阿霉素、三氧化二砷和维奈托克可显著诱导AML细胞系Molm13和MV411的LINC00987表达。下调LINC00987的表达可抑制阿糖胞苷诱导的Molm13细胞凋亡。进一步研究发现,LINC00987共表达基因可富集于细胞色素P450(cytochrome,P450,CYP450)介导的氧化应激通路/网络,且LINC00987的表达与CYP450家族基因CYP11B1、CYP2U1和CYP2C9的表达水平呈正相关。下调LINC00987的表达则可抑制阿糖胞苷诱导的CYP11B1、CYP2U1和CYP2C9的mRNA表达。结论:LINC00987可以作为AML的预后标志物,其可能通过CYP450介导的氧化应激途径促进阿糖胞苷诱导的AML细胞凋亡。

Bone marrow microRNA-34a is a good indicator for response to treatment in acute myeloid leukemia

Background:microRNA 34a(miR 34a)had been reported to have a diagnostic role in acute myeloid leukemia(AML).However,its value in the bone marrow(BM)of AML patients,in addition to its role in response to therapy is still unclear.The current study was designed to assess the diagnostic,prognostic,and predictive significance of miR 34a in the BM of AML patients.Methods:The miR.34a was assed in BM aspirate of 82 AML patients in relation to 12 normal control subjects using qRT-PCR.The data were assessed for correlation with the relevant dinical critenia,response to therapy,disease-free survival(DFS),and overall survival(OS)rates.Results:miR.34a was significantly downregulated in AML patients[0.005(3.3×10^(-6)-1.32)],compared to the control subjects[0.108(3.2× 10^(-4)-1.64),p=0.021].The.median relative quantification(RQ)of miR-34a was 0.106(range;0-32.12).The specifaity,sensitivity,and area under the curve(AUC)for the diagnosis of AML were(58.3%,69.5%,0.707,respectively,p=0.021).patients with upregulated miR-34a showed decreased platelets count<34.5 × 10^(9)/L,and achieved early complete remission(CR,p=0.031,p=0.044,respectively).Similarly,patients who were refractory to therapy showed decreased miR 34a levels in comparison to those who achieved CR[0.002(0-0.01)and 0.12(0-32.12),respectively,p=0.002].Therefore,miR 34a could significantly identify patients with CR with a specificity of 75%and sensitivity of 100%at a cut-off of 0.014(AUC=0.927,p=0.005).There was no considerable association between miR-34a expression and survival rates of the induded AML patients.Condusion:miR-34a could be a beneficial diagnostic biomarker for AML patients.In addition,it serves as a good indicator for response to therapy,which could possibly identify patients who are refractory to treatment with 100%sensitivity and 75%specificity.

50岁以上AML患者总体生存及预后影响因素分析

目的:探讨50岁以上急性髓系白血病患者生存情况和预后影响因素。方法:回顾性分析本院2016年1月至2021年6月收治的50岁以上急性髓系白血病患者共222例的临床资料,采用Kaplan-Meier方法评估总体生存率,Cox回归模型评估预后影响因素。结果:全部患者1、3年总体生存率分别为46.8%、28.8%,随访时间段内获得缓解的患者复发率为57%。单因素及多因素分析结果均显示,年龄大、MLL家族融合基因、PHF6基因突变、TP53基因突变、不耐受标准的治疗方案、未获得完全缓解、复杂染色体核型、+mar染色体核型、inv(3)染色体核型与不良预后显著相关(均P<0.05)。融合基因阴性、AML-ETO融合基因阳性在本研究人群中无明显生存优势。在获得完全缓解的患者中,是否获得MRD阴性的患者总体生存率无显著差异。结论:50岁以上急性髓系白血病患者总体预后差,复发率高,预后受多因素影响且有该人群自身特点。

基于AML的分布式开放控制系统的虚拟调试技术研究

目前,制造系统对单件小批量产品生产柔性及智能化要求越来越高,虚拟调试作为数字孪生在工业界的重要应用,通过在虚拟空间中对制造系统进行数字化验证及仿真优化,从而实现实际物理系统一次调试成功。文章研究虚拟调试的体系架构和实现方法,基于自动化标记语言(Automation Markup Language,AML)及IEC61499标准实现了生产单元的虚拟调试,并给出实际应用案例。

Acute Leukemia in Niger: Epidemiological, Diagnostic and Therapeutic Aspects

Objective: Improve the care of patients followed for acute leukemia in the Oncohematology department of the National Hospital of Niamey. Methods: This was a prospective study, over a period of 2 years from January 1, 2018 to December 31, 2019, in patients with acute leukemia in the Oncohematology department of the National Hospital of Niamey (HNN), whose diagnosis was made on a blood smear associated with a myelogram and immunophenotyping and who were consenting. Results: We collected 25 cases of acute leukemia confirmed by myelogram and immunophenotyping. The mean age of the patients was 31.32 years, with a predominance of women, a sex ratio of 0.92. Pupils and students were in the majority with 40% and most came from the Niamey region, i.e. 68%. Anemic syndrome was the most common clinical sign in 96%. ALL predominated in 64% of cases. On the blood count, the hyperleukocytosis was more marked in AML (mean white count: 197256.6 elts/mm3) than in ALL (137891.6 elts/mm3), it was the same for thrombocytopenia which is more marked in AML (75588.89/mm3) than in ALL (52156.25/mm3). Therapeutically, 52% of patients received chemotherapy. The mean overall survival was 16.223 ± 3.191 months, including a mean survival for AML of 6.853 ± 1200 months compared to 21.720 ± 5.920 months for ALL. Conclusion: Acute leukemia still remains a major problem in our context, due to the precariousness of limited financial, diagnostic and therapeutic resources. Thus reflecting in our results, the increasing number of cases, the diagnostic delay and the guarded prognosis. This is the reality in several other countries in the sub-region and even in certain developed countries.