Objectives Multiple myeloma (MM) is a malignant plasma cell disorder. The most widely accepted staging system for MM is the revised International Staging System based on cytogenetic and clinical biomarkers. The circulating clonal plasma cells (CPCs) were reported to have potential prognostic impact on MM. Among various diagnostic approaches, multiparametric flow cytometry (FCM) offers heightened sensitivity, minimal invasiveness and reproducibility. We conducted a meta-analysis to evaluate the prognostic value of quantifying CPCs via FCM in newly diagnosed symptomatic MM (NDMM) patients.Design Systematic review and meta-analysis.Data source PubMed, Web of Science, Embase and references of included studies.Eligibility criteria for selecting studies We included observational studies that evaluated the prognostic value of CPCs detected by FCM in NDMM.Data extraction and synthesis Data were screened and extracted independently by two investigators. The pooled results originated from random effects models. The primary endpoint was overall survival (OS). The secondary endpoint was progression-free survival (PFS). To evaluate the prognostic value of CPCs in NDMM, HRs and their 95% CI for both OS and PFS were derived using COX multivariable models. These values were then used to compute the pooled estimated effect.Results Our meta-analysis encompassed a total of 2704 NDMM patients from 11 studies up to 27 August 2022. The pooled HR for OS and PFS in CPC-positive (CPCs+) group and CPC-negative group were 1.95 (95% CI 1.24 to 3.07) and 2.07 (95% CI 1.79 to 2.39), respectively. The autologous stem cell transplantation (ASCT) failed to eliminate the adverse impact on OS and PFS. The heterogeneity may stem from the use of novel agents or traditional chemotherapy as initial treatment.Conclusion This meta-analysis indicates CPCs+ had an adverse impact on the prognosis of NDMM patients in the total population, and the adverse impact could not be eliminated by ASCT.PROSPERO registration number CRD42021272381.

目的 分析t(16;21)(p11;q22)/FUS-ERG急性髓系白血病(AML)患者的临床特点.方法 纳入2017 年1 月～2021 年 7 月我科收治的 6 例t(16;21)(p11;q22)/FUS-ERG AML患者及汇总文献报道的90 例成人t(16;21)(p11;q22)/FUS-ERG AML患者.收集其一般临床资料、免疫分型、基因检测、染色体核型分析及NGS检测结果、治疗方案及疗效、随访结果并分组进行比较.结果 6 例t(16;21)(p11;q22)/FUS-ERG AML患者占同期确诊AML的0.36%,免疫表型CD34、CD33、CD117、CD56 均为阳性.FUS-ERG融合基因均为阳性,4 例患者染色体可见t(16;21)(p11;q22).6 例患者均接受化疗,其中4 例1 个疗程完全缓解(CR),1 例 2 个疗程CR,1 例 1 个疗程因感染死亡.3 例单纯化疗患者生存期分别为16.2 个月、14.3 个月和10.7 个月;2 例化疗联合异基因造血干细胞移植(allo-HSCT)治疗,生存期分别为 9.1 个月和 19.4 个月.汇总文献结果显示,年龄＜60 岁患者1 个疗程CR率高于年龄≥60 岁患者,无髓外病变患者1 个疗程CR率高于髓外病变患者(P＜0.05);化疗联合 HSCT 患者中位总生存期(OS)高于单纯化疗患者(P＜0.001).结论 t(16;21)(p11;q22)/FUS-ERG AML应纳入预后不良组,推荐尽早行allo-HSCT改善生存质量.

Objective To observe the expressions of hypoxia-inducible factor-1α(HIF-1α)and glycolysis-related genes in patients with acute myeloid leukemia(AML),and to explore the influence of HIF-1α on the prognosis of AML patients and its possible mechanism.Methods From July 2015 to July 2018,90 patients with initially diagnosed AML(AML group)and 18 healthy allogeneic hematopoietic stem cell transplantation donors(control group)were detected the mRNA relative expressions of HIF-1α in the bone marrow mononuclear cells and glycolysis-related genes(HK2,PFKM,ALDOA,PGK1,PDK1,LDHA)by real-time fluorescence quantitative PCR in the First Affiliated Hospital of Zhengzhou University and Children's Hospital Affiliated to Zhengzhou University.Spearman correlation analysis was done to evaluate the correlations of the relative expressions of HIF-1α mRNA with the relative expressions of HK2,PFKM,ALDOA,PGK1,PDK1 and LDHA mRNAs in AML patients.AML group received"3+7"regimen to induce chemotherapy,and 45 patients achieved complete remission and 45 patients did not achieve complete remission after one course of chemotherapy.The relative expression of HIF-1α mRNA was compared between those with and without complete remission.Taking the median relative expression of HIF-1α mRNA(2.0403)as the boundary,AML group was divided into 45 patients with HIF-1α mRNA relative expression＜2.040(low-expression group)and 45 patients with HIF-1α mRNA relative expression ≥2.040(high-expression group),and the FAB classification,white blood cell count,platelet count,hemoglobin,bone marrow original cell ratio,prognosis stratification and complete remission rate after one-course chemotherapy were compared between two groups.Univariate and multivariate Cox regression analyses were done to evaluate the influencing factors of poor prognosis of AML patients.After 1-72 months of follow-up,the survival was recorded in high-and low-expression groups.Kaplan-Meier survival curve was plotted,and the log-rank method was used to compare the event-free survival time and overall survival time between two groups.Results The relative expressions of HIF-1α,HK2,PFKM,ALDOA,PGK1,PDK1 and LDHA mRNAs were higher in AML group[2.040(0.836,4.750),1.743(0.946,3.752),1.200(0.595,2.701),4.212(2.980,6.941),3.254(1.612,5.443),2.160(1.140,5.724),2.621(1.425,6.094)]than those in control group[1.000(0.945,1.074),1.000(0.881,1.095),1.000(0.600,1.238),1.000(0.841,1.256),1.000(0.921,1.220),1.035(0.842,1.200),1.035(0.829,1.209)](P＜0.05).The relative expression of HIF-1α mRNA in AML group was positively correlated with the relative expressions of HK2,PFKM,ALDOA,PGK1,PDK1 and LDHA mRNAs(P＜0.05).The relative expression of HIF-1α mRNA after one-course chemotherapy was lower in patients with complete remission[1.800(0.793,3.075)]than that in patients without complete remission[2.919(0.838,5.812)](Z=2.719,P=0.008).There were no significant differences in the gender ratio,age,FAB classification,white blood cell count,platelet count,hemoglobin,bone marrow original cell ratio,prognosis stratification and rate of complete remission after one-course chemotherapy between high-expression group and low-expression group(P＞0.05).Prognosis stratification(HR=1.840,95％CI:1.245-2.719,P=0.002),complete remission after one-course chemotherapy(HR=2.074,95％CI:1.155-3.725,P=0.015)and relative expression of HIF-1α mRNA(HR=1.863,95％CI.1.063-3.265,P=0.030)were the influencing factors of poor prognosis of AML patients.The median follow-up time was 21 months.The event-free survival time and overall survival time were shorter in high-expression group[(10.67±9.26),(12.78± 11.39)months]than those in low-expression group[(21.60±15.29),(21.22±15.47)months](x2=22.450,P＜0.001;x2=4.720,P=0.030).Conclusions The expression of HIF-1α increases in AML patients.The patients have higher risk of poor prognosis when the expression of HIF-1α is high,the pretreatment prognosis stratification is poor,and the patients achieve no complete remission after one-course chemotherapy.HIF-1α may accelerate AML progression and drug resistance by activating glycolysis.

Objective:To explore the expression of fructose bisphosphate aldolase A (ALDOA) in the bone marrow of patients with acute myeloid leukemia (AML) and the correlation with clinical features and prognosis.Methods:The bone marrow samples of 90 newly diagnosed AML (non-acute promyelocytic leukemia) patients and 18 allogeneic hematopoietic stem cell transplantation donors who were treated from January 2013 to December 2015 in the First Affiliated Hospital of Zhengzhou University and the Children's Hospital Affiliated to Zhengzhou University were collected. The relative expression level of ALDOA mRNA in bone marrow samples was detected by using real-time quantitative polymerase chain reaction (qRT-PCR). Clinical data of these patients were retrospectively analyzed, and the patients were divided into continuous complete remission (CR) group and refractory recurrent (RR) group according to the clinical response and follow-up results. The differences of the relative expression level of ALDOA mRNA between AML group and the normal control group, CR group and RR group were analyzed. Univariate and multivariate Cox regression risk model were used for analysis of factors influencing prognosis of AML patients.Results:The relative expression level of ALDOA mRNA in AML group was higher than that in normal control group [(5.71±0.44) vs. (1.10±0.08), t = 4.74, P<0.001]. The relative expression level of ALDOA mRNA in the RR group was higher than that in the CR group [(6.69±0.67) vs. (4.30±0.36) , t = 2.79, P < 0.001]. In addition, there were statistically significant differences in the proportion of patients with ALDOA mRNA high expression and those with ALDOA mRNA low expression stratified by the number of white blood cell, the proportion of bone marrow blasts and whether complete remission could be achieved or not after 1 course of induction therapy (all P < 0.05). Overall survival in patients with ALDOA high expression was worse than that in patients with ALDOA low expression ( χ2 = 5.59, P = 0.018). Multivariate analysis showed that white blood cell count, prognosis stratification, whether complete remission could be achieved or not after 1 course of induction therapy and ALDOA expression were the independent prognostic factors for the death of AML patients (all P < 0.05). Conclusions:ALDOA may play an important role in the development and progression of AML, and the expression level of ALDOA in the bone marrow can be used as an index for the prognosis assessment of AML patients and may be a potential therapeutic target for AML.

[This retracts the article DOI: 10.21037/atm-20-4558.].

Objective Acute lymphoblastic leukemia (ALL) is a malignant disease most commonly diagnosed in adolescents and young adults. This study aimed to explore potential signatures and their functions for ALL. Methods Differentially expressed mRNAs (DEmRNAs) and differentially expressed long non-coding RNAs (DElncRNAs) were identified for ALL from The Cancer Genome Atlas (TCGA) and normal control from Genotype-Tissue Expression (GTEx). DElncRNA–microRNA (miRNA) and miRNA–DEmRNA pairs were predicted using online databases. Then, a competing endogenous RNA (ceRNA) network was constructed. Functional enrichment analysis of DEmRNAs in the ceRNA network was performed. Protein–protein interaction (PPI) network was then constructed. Hub genes were identified. DElncRNAs in the ceRNA network were validated using Real-time qPCR. Results A total of 2,903 up- and 3,228 downregulated mRNAs and 469 up- and 286 downregulated lncRNAs were identified for ALL. A ceRNA network was constructed for ALL, consisting of 845 lncRNA-miRNA and 395 miRNA–mRNA pairs. These DEmRNAs in the ceRNA network were mainly enriched in ALL-related biological processes and pathways. Ten hub genes were identified, including SMAD3, SMAD7, SMAD5, ZFYVE9, FKBP1A, FZD6, FZD7, LRP6, WNT1, and SFRP1. According to Real-time qPCR, eight lncRNAs including ATP11A-AS1, ITPK1-AS1, ANO1-AS2, CRNDE, MALAT1, CACNA1C-IT3, PWRN1, and WT1-AS were significantly upregulated in ALL bone marrow samples compared to normal samples. Conclusion Our results showed the lncRNA expression profiles and constructed ceRNA network in ALL. Furthermore, eight lncRNAs including ATP11A-AS1, ITPK1-AS1, ANO1-AS2, CRNDE, MALAT1, CACNA1C-IT3, PWRN1, and WT1-AS were identified. These results could provide a novel insight into the study of ALL.

Identifying new prognostic biomarkers and selecting treatment regimens based on them can improve outcomes of adult patients with B-cell acute lymphoblastic leukemia (B-ALL). Extracellular matrix protein 1(ECM1) is a glycoprotein involved in many biologic processes. Here we aimed to determine the expression and the prognostic value of ECM1 in B-ALL. One hundred and six newly-diagnosed B-ALL patients (seventy-one adult patients and thirty-five children patients) were enrolled from March 2013 to December 2018. The ECM1 transcript levels were significantly different among different disease state. Among 71 adult B-ALL patients, ECM1-high group has a higher initial platelet count( p =0.004)，more BCR-ABL fusion positive patients ( p =0.004) and poor risk patients ( p =0.021) than ECM1-low group, whereas no significant relationship with any other clinical characteristics was observed. ECM1-high group had significantly lower 3-year OS (11.4% vs. 36.1%, p =0.015) and 3-year RFS (9.7% vs. 29.4%, p =0.047) compared to ECM1-low group. In the multivariate Cox regression model, high ECM1 expression was an independent adverse prognostic factor for OS(HR=3.0(1.4-6.6), p =0.007). Our data demonstrated that the expression of ECM1 could serve as a novel prognostic biomarker for adult patients with B-ALL.

The imbalance between the proliferation and apoptosis of B-cell precursors is an important contributor to the pathogenesis of B-cell precursor acute lymphoblastic leukemia (BCP-ALL), while its specific regulatory mechanism remains perplexing. This study aimed to expound the underlying mechanism of the proliferation and apoptosis of BCP-ALL cells from the perspective of non-coding RNA. In this study, long non-coding RNA colorectal neoplasia differentially expressed (LncRNA CRNDE) was upregulated in the bone marrow of BCP-ALL patients and BCP-ALL cell lines (NALM-6 and RS4;11). Functionally, LncRNA CRNDE knockdown restrained cell proliferation and boosted cell apoptosis in NALM-6 and RS4;11 cells. The subsequent investigation confirmed that LncRNA CRNDE bound to miR-345-5p and negatively regulated miR-345-5p expression. The overexpression of miR-345-5p suppressed cell proliferation and boosted cell apoptosis in NALM-6 and RS4;11 cells. Further experiments revealed that miR-345-5p downregulated cyclic AMP response element-binding protein (CREB) expression by targeting its mRNA directly. CREB overexpression reversed the effect of miR-345-5p mimic on cell proliferation and apoptosis in NALM-6 and RS4;11 cells. Finally, in vivo experiments showed that LncRNA CRNDE knockdown prolonged the survival of mice xenotransplanted with NALM-6 cells. In conclusion, LncRNA CRNDE upregulated CREB expression by suppressing miR-345-5p, thus promoting cell proliferation and reducing cell apoptosis in BCP-ALL.

OBJECTIVE To compare the gene mutational spectrum between elderly and young adults with acute myeloid leukemia(AML) based on next generation sequencing(NGS). METHODS The specimens of 250 AML patients in first affiliated hospital of Zhengzhou University from January 2018 to November 2018 were collected and analyzed retrospectively. The mutation of 22 related genes were detected by using AML NGS chips. Then, the differences between elderly (≥60 years old) and young adults (＜60 years old) were compared. RESULTS The most frequent mutations of 250 patients were as follows: NPM1(22.4%), FLT3-ITD(18.8%), NRAS(17.2%), DNMT3A(14.4%), TET2(11.6%), IDH2(9.6%), Biallelic CEBPA(8.8%), Moallelic CEBPA(8.4%), KIT(8.4%), RUNX1(7.6%), IDH1(7.6%), ASXL1(6.0%), U2AF1(5.2%), SRSF2 (3.2%), SF3B1(3.2%), TP53(2.4%), KRAS(2.0%). The NPM1, CEBPA, DNMT3A mutation significantly increased in intermediate prognosis group while KIT significantly increased in favourable prognosis group. The TET2 and IDH2 mutation rate in elderly patients were significantly higher than that in young patients (21.8% vs 8.7%) (χ2=7.180, P=0.007) and (20.0% vs 6.7%) ( χ2=8.788, P=0.003) respectively. Compared with young patients, the frequencies of DNA methylation and demethylation mutations (including DNMT3A, TET2, IDH1, IDH2) and RNA splicing enzyme mutations (inc-luding SRSF2, SF3B1, U2AF1, ZRSR2) in elderly patients significantly increased(67.3% vs 36.4%) (χ2=16.653, P=0.000) and (23.6% vs 8.7%)(χ2=9.041, P=0.003) respectively. CONCLUSION The gene mutational spectrum in elderly and young adult AML shows heterogeneity. Compared with young adults, the frequencies of DNA methylation and demethylation mutations and RNA splicing enzyme mutations in elderly patients significantly increase.

Acute myeloid leukemia (AML) is a hematological malignancy derived from immature myeloid cells, which have the characteristics of abnormal proliferation and differentiation. Glycolysis has been a popular topic of research in recent years, with increasing uptake and consumption of glucose. The present study aimed to investigate the glycolysis of tumor cells in patients with AML; in particular, how programmed cell death 1 ligand 1 (PD‑L1) regulates tumor cells glycolysis using real time PCR (RT‑PCR), western blotting and flow cytometry. PD‑L1 high expression predicted poor outcome in patients with AML in the public database Gene Expression Profiling Interactive Analysis. PD‑L1 expression was decreased in the samples from patients with AML with complete remission compared to that in patients with relapsed or refractory AML. In AML cell lines, glycolysis‑associated genes ALDOA, PGK1, LDHA and HK2 were highly expressed in a PD‑L1 high‑expressed cell line. Overexpressed PD‑L1 enhanced glucose consumption and the extracellular acidification rate, accompanied by decreased apoptosis and accumulation of cells in the S phase. In contrast, the apoptosis rate of tumor cells and the percentage of cells in the S phase were significantly increased following PD‑L1 knockdown in the THP1 cell line. HK2 and LDHA expression decreased after AML tumor cells were treated with Akt inhibitor or rapamycin. In addition, the PD‑L1‑overexpressed cell line (PD‑L1‑OV) MOLM‑13 exhibited rapid tumor progression. Glycolysis‑associated genes were highly expressed in tumor tissues of PD‑L1‑OV MOLM‑13, with increased Ki67. Based on these findings, PD‑L1 may be considered as a suitable marker for prognosis and treatment in the clinical setting.

Background: Leukemia is characterized by the presence of highly malignant tumors formed in the hematopoietic system. Artesunate (Art), a semi-synthetic derivative of artemisinin, is commonly used as an antimalarial drug and has been proven to possess anticancer potential. Methods: In this study, the effect of Art on the proliferation and stemness of human acute promyelocyte leukemia HL-60 cells and acute myeloid leukemia KG1a cells was investigated. Flow cytometry, colony formation assay, the protein expressive levels of survivin, P21, cleaved caspase 3, Bax, Bcl-2, Ki67 were detected the effect of Art on HL-60 and KG1a cells proliferation and apoptosis. At the same time, cell sphere formation assay and the protein expressive levels of CD44, SOX2, ALDH1 and OCT4 were used to analyze the effects of Art on cancer stem cell-like property in vitro. The orthotopic xenograft mouse models were established by using KG1a cells in BALB/c athymic nude mice. Tumor weigh was detected. The protein levels of survivin and Ki67 were detected by immunohistochemistry assays. Results: Art induced cell apoptosis and inhibited cell proliferation and stemness in a dose-dependent manner. In the meantime, the results exhibited that Art inhibited the growth and stemness of transplanted tumors via the suppression of the MEK/ERK and PI3K/Akt pathway. Conclusions: Our present study provides new insights into the mechanisms of Art's anticancer potential in leukemia.

目的 提高对慢性中性粒细胞白血病(CNL)的认识.方法 对郑州大学第一附属医院收治的1例合并左下肢动脉血栓的CNL患者的诊疗经过进行分析总结,并复习相关文献.结果 该患者以左下肢动脉血栓为首发临床表现,白细胞持续性升高,以中性分叶核及杆状核为主,CSF3R基因突变检测阳性,确诊为CNL.患者最终因左下肢截肢术后伤口愈合差且合并感染而死亡.结论 CNL早期诊断困难,需与类白血病反应及其他骨髓增殖性疾病等相鉴别,CSF3R基因突变检测有助于诊断.

Objective To investigate the efficacy and safety of domestic bortezomibˉbased chemotherapy for patients with multiple myeloma (MM). Methods The clinical data of 60 MM patients treated with domestic bortezomibˉbased chemotherapy regimen (the observation group) in the First Affiliated Hospital of Zhengzhou University from April 2018 to October 2018 were retrospectively analyzed, which were compared with 112 MM patients treated with original treatment regimen (the control group) at the same hospital from November 2010 to November 2014. According to the disease stage, the patients were divided into newly diagnosed MM (NDMM) group and relapsed refractory MM (RRMM) group, and efficacy and adverse reactions of domestic bortezomib were evaluated. Results The total response rate (ORR) of the observation group was 71.7% (43/60), severe complete response (sCR) + complete response (CR) rate was 16.7% (10/60), very good partial response (VGPR) rate was 18.3% (11/60), and partial response (PR) rate was 36.7% (22/60). The ORR of NDMM group (45 cases) and RRMM group (15 cases) was 82.2% (37/45) and 40.0% (6/15), respectively, and the difference was statistically significant (χ2＝ 9.877, P < 0.05). There was no significant difference between ISS stage Ⅰ+Ⅱ and stage Ⅲ [ORR: 75.7% (28/37) vs. 65.2% (15/23), respectively; χ2＝0.764, P >0.05]. ORR and CR rates in the NDMM group and RRMM group of the observation group and the control group were not statistically different (all P>0.05). In the treatment of bortezomibˉbased chemotherapy, the common adverse reaction was peripheral neuropathy, mostly belonging to grade 1-2. Other side effects included hematocytopenia, gastrointestinal events and herpes zoster, which could be alleviated or restored to normality after supportive treatments. One patient died of pulmonary infection, respiratory failure and septic shock during the intermittent period of chemotherapy. Conclusion ORR of domestic bortezomibˉbased chemotherapy in treatment of the patients with MM is high, and the incidence of adverse reactions shows no significant increase compared with original drugs.

目的 探讨血清维生素D3水平在多发性骨髓瘤(MM)患者血清中的变化及其临床意义.方法 选择76例初治MM患者(MM组)及同期体检科的18例健康志愿者(对照组)作为研究对象,检测血清维生素D3水平,并结合患者的β2微球蛋白(β2-MG)、血浆白蛋白、肌酐、乳酸脱氢酶等疾病活动相关指标进行分析.结果 MM组患者血清维生素D3水平明显低于对照组,差异有统计学意义(P＜0.05);Ⅲ期β2-MG患者血清维生素D3水平明显低于Ⅰ、Ⅱ期患者,差异均有统计学意义(P均＜0.05),而Ⅰ、Ⅱ期患者血清维生素D3水平比较差异无统计学意义(P＞0.05);血清维生素D3水平与β2-MG患者β2-MG、肌酐、浆细胞比例、血红蛋白、血清白蛋白有关(P均＜0.05).结论 MM患者血清维生素D3水平明显降低,血清维生素D3可以反映MM患者疾病的严重程度,对MM患者辅助诊断及预后分析有一定的价值.

Leukemia is the most frequent malignancy in children with acute myeloid leukemia (AML) as the second commonest type. Long non-coding RNA zinc finger antisense 1 (ZFAS1) has been widely reported as an oncogenic factor in multiple malignancies including AML. However, the roles and molecular mechanisms of ZFAS1 in the tumorigenesis of AML are poor defined till now. In the present study, RT-qPCR assay showed that ZFAS1 was highly expressed in bone marrow of acute leukemia patients and AML cell lines. Loss-of-function analyses revealed that ZFAS1 knockdown inhibited proliferation and promoted apoptosis in AML cells and curbed AML xenograft growth in vivo. Bioinformatics analysis and luciferase reporter assay unveiled that microRNA-150 (miR-150) could interact with ZFAS1, Myb 3' UTR and Sp1 3' UTR. Moreover, ZFAS1 acted as a molecular sponge of miR-150, giving rise to the downregulation of miR-150 level and upregulation of Myb and Sp1 levels. Moreover, miR-150 overexpression resulted in the reduction of AML cell proliferative ability and the increase of cell apoptotic rate. Additionally, the inhibition of miR-150 abrogated ZFAS1 loss-mediated anti-leukemia effects. In summary, our data demonstrated that ZFAS1 knockdown hampered AML progression by regulating miR-150/Myb and miR-150/Sp1 pathways, providing some potential biomarkers or targets for the diagnosis and treatment of leukemia.

>神经钙黏蛋白(N-cadherin)是经典的钙黏蛋白超家族成员之一,表达于神经细胞、内皮细胞、肌肉细胞和造血干细胞在内的多种正常组织中。它不仅是胚胎发育过程中原肠胚形成和神经嵴发育的重要分子,而且在结直肠癌、前列腺癌、胃癌、乳腺癌等实体肿瘤中参与调控肿瘤的浸润和转移、细胞周期和凋亡等病理过程,并与肿瘤的恶性程度和侵袭性呈

Introduction: Minichromosome maintenance 10 (MCM10) is deregulated in several malignancies including cervical cancer and urothelial carcinoma. However, the expression and biologic role of MCM 10 in esophageal squamous cell carcinoma (ESCC) is still unknown. Methods: In this study, we performed immunohistochemistry and real-time polymerase chain reaction (PCR) analysis to examine the expression of MCM10 in ESCC and adjacent normal esophageal tissues. The associations of MCM10 expression with clinicopathologic parameters of ESCC were analyzed. Ablation of MCM10 through the CRISPR/Cas9 technology was conducted and its impact on ESCC cell growth and migration was investigated. Results: The mRNA and protein expression levels of MCM10 were significantly greater in ESCC than in normal tissues (P < 0.001). The expression of MCM10 was significantly associated with age at diagnosis (P = 0.033), but not with gender, differentiation grade, invasion status, or tumor-node-metastasis (TNM) stage. Knockout of MCM10 significantly suppressed the proliferation, colony formation, and migration capacity of EC109 ESCC cells, compared to control cells harboring wild-type MCM10. Mechanistically, MCM10 depletion markedly reduced the phosphorylation of Akt. Overexpression of constitutively active Akt significantly restored the aggressive phenotype of MCM10-null EC109 cells. Conclusion: In conclusion, these results suggest that MCM10 acts as an oncogene in ESCC through activation of Akt signaling and represents a promising therapeutic target for this malignancy.

OBJECTIVE:To investigate the expression of long non coding RNA RP11-69I8.3 in acute leukemia and its clinical significance.METHODS:lncRNA RP11-69I8.3 expression was detected by RT-PCR in bone marrow samples from 17 healthy controls, 32 newly diagnosed AML patients and 32 newly diagnosed ALL patients, and 25 ALL patients of complete remission after chemotherapy. Meanwhile, the clinical data were collected and the relation of lncRNA RP11-6918.3 expression with the clinical characteristics was analyzed.RESULTS:Compared with the control group, there was no significant difference in the expression of lncRNA RP11-69I8.3 in AML group(P>0.05). lncRNA RP11-69I8.3 lowly expressed in untreated ALL group(P=0.001). Compared with the de novo ALL group, lncRNA RP11-69I8.3 was highly expressed in complete remission ALL group (P<0.013). In 32 de novo ALL patients,the expression of lncRNA RP11-69I8.3 in children was significantly lower than that in adult(P=0.017). There was no correlation of the expression of lncRNA RP11-69I8.3 with the sex, WBC count, HB level, Plt count, LDH level, T or B type, ratio of bone marrow blast cell, BCR/ABL and WT1 fusion gene expression, chromosome karyotype, extramedullary infiltration, whether complete remission after one chemotherapy, whether relapse. In 26 B-ALL patients, there was no correlation between lncRNA RP11-69I8.3 and the immunophenotype.CONCLUSION:The expression of lncRNA RP11-69I8.3 in the untreated AML is not significantly different from the control group. lncRNA RP11-69I8.3 is low expressed in ALL group, highly expressed in ALL group with complete remission. In untreated ALL, the expression of lncRNA RP11-69I8.3 in children is significantly lower than that in adult. In B-ALL patients, the lncRNA RP11-69I8.3 is not relevant with the immunophenotype.

Objective To explore the risk factors for death in patients with acute leukemia complicated with multidrug resistant Escherichia coli (MDR-E.coli) bloodstream infection.Methods A total of 106 acute leukemia patients complicated with MDR-E.coli bloodstream infection received appropriate antibiotic treatment for 2 weeks according to the drug sensitivity test results,and were divided into survival group (n=82) and death group (n=24) according to the survival status after 30 d treatment.Multivariate regression analysis was used to analyze the risk factors for death after 30 d treatment.Results The proportion of ＞45-year old patients (45.83％),incidence of septic shock (62.50％),and glucocorticoid therapy application rate in 30 d before treatment (45.83 ％) in death group were significantly higher than those in survival group (23.17％,3.66％,24.39％) (P＜0.05).Multivariate regression analysis results showed septic shock during treatment (OR=47.33,95 ％ CI:10.14-220.83,P=0.000) and glucocorticoid therapy application rate in 30 d before treatment (OR=4.13,95％CI:1.05-16.20,P=0.042) were the risk factors for death after 30 d treatment in patients with acute leukemia complicated with MDR-E.coli bloodstream infection.Conclusion Septic shock during treatment and glucocorticoid therapy before treatment are involved in death after 30 d treatment in patients with acute leukemia complicated with MDR-E.coli bloodstream infection.

OBJECTIVE:To explore the differences of CD146 expression in adult and children's acute B cell lymphoblastic leukemia(B-ALL), and its relation with clinical features, molecular biological and cytogenctic claracteristics.METHODS:The expression of CD146 in bone marrow samples from adult and children's B-ALL patients were detected by flow cytometry (FCM) and the relation of CD146 abnormal high expression with the patients' clinical features, molecular biological and cytogenetical characteristics, as well as other antigens were analyzed.RESULTS:The abnormal high expression rates of CD146 in adult and children's B-ALL patients were 29.17% and 9.09% respectively, showing that the expression rate of CD146 in adult patients was higher than that in children's patients(P<0.05). In adult B-ALL, CD146 was positively related with CD64 and CD117, while in children's B-ALL CD146 was positively related with CD71 and CD58 (P<0.05). After 1 course of standardized chemotherapy, the complete remission rates in adult and children's B-ALL patients with abnormal high expression of CD146 both were low as compared with adult and children's B-ALL without abnormal high expression of CD146 (P<0.05).CONCLUSION:The expression rate of CD146 in adult B-ALL is higher than that in children's B-ALL. The CD146 positively relates with poor prognostic antigens, the CD146 may be one poor prognosis marker.