The Diagnostic Value of Peripheral Blood Cell Parameters for Early Recognition of Myelodysplastic Syndrome / 中国实验血液学杂志

OBJECTIVE@#To evaluate the diagnostic value of peripheral blood cell parameters for early recognition of myelodysplastic syndrome (MDS) patients.@*METHODS@#The clinical and laboratory data of 86 patients with MDS and 72 patients with non-malignant clonal anemia treated in first diagnosed in the Second Hospital of Hebei Medical University from January 1, 2015 to December 31, 2017 was retrospectively analyzed. The peripheral blood cell parameters of the patients in two groups were analyzed, generated the receiver operator characteristic curve (ROC curve) from the statistically significant parameters, the binary logistic model was build to calculate and compare the area under the ROC curve (AUC) combined with multiple indicators and individual indicators, sensitivity, specificity, positive and negative likelihood ratio, and diagnostic accuracy, the diagnostic efficacy of the patients was analyzed.@*RESULTS@#Compared with patients in the non-malignant clonal anemia group ,white blood cell count (WBC), neutrophil percentage (NE%), eosinophil percentage (E%), eosinophil absolute value (E#), platelet count (PLT), platelet specific volume (PCT%) in the MDS patients were significantly reduced; while percentage of lymphocytes (LY%), basophilic percentage (B%), and the width of platelet distribution (PDW) significantly increased. The several ROC curves with the above indicators were established, which showed that AUC@*CONCLUSION@#PDW, B% and LY% in peripheral blood cell parameters have certain diagnostic value for early recognition of MDS.

Effect of Montelukast on T-lymphocyte subsets and advanced oxidation protein products in immune thrombopenic purpura model mice / 中国免疫学杂志

Objective:To investigate the effect of Montelukast on T-lymphocyte subsets, cytokines and advanced oxidation protein products ( AOPP ) in immune thrombopenic purpura ( ITP ) model mice. To analyze the principle of the treatment by Montelukast. Methods: Forty ITP mice were randomly divided into control group,model group,Montelukast low dose group(3 mg/kg) and Montelukast high dose group(12 mg/kg). ITP model mice were successive administration for 14 days after building models for 7 days. Platelet counts,the index of thymus and spleen were calculated. T-lymphocyte subsets were detected by flow cytometry. IL-6,TNF-α,AOPP were detected by enzyme linked immunosorbent assays. Results: Comparison with control group,the PLT,thymus index and spleen index,CD8+,IL-6,TNF-α,AOPP of model group mice were significantly increased (P＜0. 05) while CD3+,CD4+,CD4+/CD8+were significantly decreased (P＜0. 05). Comparison with model group,PLT,thymus index and spleen index,CD8+,IL-6,TNF-α,AOPP of low dose group and high douse group mice were significantly decreased (P＜0. 05) while CD3+,CD4+,CD4+/CD8+were significantly increased (P＜0. 05). Conclusion: Montelukast can cure ITP regulate immune disorders,eliminate accumulation of AOPP and reduce level of IL-6 and TNF-α.

Efficacy and Safety of Lenalidomide in the Treatment of Multiple Myeloma: A Systematic Review and Meta-analysis of Randomized Controlled Trials / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Lenalidomide has emerged as an important treatment for patients with multiple myeloma (MM). However, its role in the management of MM is still controversial and requires further clarification. The aim of this study was to evaluate efficacy and safety of lenalidomide for MM using a meta-analysis.</p><p><b>METHODS</b>We searched the electronic databases including: PubMed, EMBASE and the Cochrane Center Register of Controlled Trials. Seven randomized clinical trials were identified, which included a total of 2357 patients with MM who received lenalidomide-containing, noncontaining lenalidomide regimens or placebo as induction therapy or maintenance therapy. The outcomes included overall response (OR) rate, complete response (CR) rate, 3-year progression-free survival (PFS) rate, 3-year overall survival (OS) rate, and different types of treatment-related adverse events. We calculated the risk ratios (RRs) as well as their 95% confidence intervals of these outcomes and pooled the results using RevMan 5.2 software.</p><p><b>RESULTS</b>For patients with previously untreated MM, OR rate and CR rate was significantly higher in lenalidomide-containing group than the control group. For relapsed or refractory MM patients, lenalidomide-containing regimens significantly improved the OR rate, CR rate, 3-year PFS rate and 3-year OS rate. With regard to MM patients after autologous stem cell transplantation, lenalidomide maintenance therapy significantly improved 3-year PFS rate but did not result in improved 3-year OS rate. In terms of toxicities, lenalidomide therapy has a higher rate of Grade 3-4 grade cytopenias, infection, deep-vein thrombosis, and diarrhea. Furthermore, the incidence of second primary malignancies was significantly higher in the lenalidomide group.</p><p><b>CONCLUSIONS</b>The lenalidomide-containing regimens as induction therapy clearly increased response rates and improved intervals of survival with acceptable toxicity rates for patients with MM. However, when physicians choose to use the lenalidomide as maintenance therapy, whether the benefits outweigh the risks should be taken into account.</p>

Effects of As2O3 on the Proliferation, Differentiation and Apoptosis of HL-60 Cells and Its Related Mechanisms / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the effects of arsenic trioxide (As2O3) on the proliferation, differentiation and apoptosis of HL-60 cells in vitro and explore the underlying mechanisms.</p><p><b>METHODS</b>After HL-60 cells were treated with different concentration of As2O3, the cell proliferation was determined by MTS/PES method, the differentiation state was detected by the nitroblue tetrazolium (NBT) reduction test; flow cytometry was used to analyze the apoptosis and expression of CD11b. In addition, SYBR Green real-time RT-PCR was used to measure the mRNA levels of C-FES, BCL-2, BAX, survivin , P21 and P27.</p><p><b>RESULTS</b>As2O3 could obviously inhibit the proliferation of HL-60 cells, and the effect was in dose- and time-dependent manners (r=-0.967; r=-0.954). Low concentration (0.1, 0.5 and 1.0 µmol/L) of As2O3 could significantly promote the differentiation of HL-60 cells, the cells exhibited a higher NBT-reducing ability and expressed far more CD11b antigens. High concentration (2.5 and 5.0 µmol/L) of As2O3 induced HL-60 cell apoptosis, but the ability of promoting differentiation decreased. The expression of C-FES mRNA significantly increased after being treated with As2O3 at the concentrations 1.0 and 5.0 µmol/L, and the former is more obvious, which confirmed that C-FES mRNA level paralleled the cell differentiation degree. Also, the expression of BCL-2 and survivin significantly decreased, while the expression of BAX, P21 and P27 was significantly upregulated in HL-60 cells after being treated with 5.0 µmol/L As2O3.</p><p><b>CONCLUSION</b>As2O3 can significantly suppress cell proliferation, promote the differentiation and induce the apoptosis in HL-60 cells, and the mechanism of As2O3 anti-tumor activity may be involved in the regulation of C-FES, cell cycle and apoptosis-related genes.</p>

Expression of c-fes gene in leukemia cells and its clinical significance / 中国实验血液学杂志

This study was purposed to investigate the expression of c-fes gene in leukemia patients and its clinical significance. The expression of c-fes mRNA in bone marrow cells from 121 cases of acute and chronic leukemia patients, and the expression of c-fes mRNA in peripheral blood mononuclear cells of 20 normal persons were detected by real time-quantitative reverse transcription polymerase chain reaction (RQ-PCR). The results showed that the level of c-fes mRNA in AML patients was higher than that in normal controls [(48.017 +/- 57.170) x 10(-3) vs (0.152 +/- 0.398) x 10(-3)] (p < 0.0001); but there was no significant differences of level of c-fes mRNA between samples of ALL and normal controls(0.047 +/- 0.068) x 10(-3) vs(0.152 +/- 0.398) x 10(-3) (p>0.05); the level of c-fes mRNA in CML patients was higher than that in normal persons (21.605 +/- 24.818) x 10(-3) vs (0.152 +/- 0.398) x 10(-3) (p < 0.0001). The positive expression rate of c-fes gene in CML-CP patients (80%) was higher than that in CML-AP patients (66.7%) and CML-BP (28.6%) patients. In AML patients, c-fes gene was expressed higher in M(2) (80.77%) and M(3) (92.86%) patients. The remission rate of AML (except M(3))patients who had expression of c-fes gene was 81.08%, which was higher than that of patients with no expression of c-fes gene (40.00%). It is concluded that c-fes gene expression was found in myeloid leukemias, whereas low or no expression in lymphocytic leukemias. The differentiation of myelocytic cells may be related to c-fes gene. All AML (except M(3))patients with high level of c-fes mRNA may get good prognosis.

Effects of imatinib on the expression of SHIP gene and apoptosis of K562 cells / 肿瘤

Objective: To observe the changes of SHIP, caspase-1, caspase-3, caspase-9 and bcl-2 gene expression levels in K562 cells after mesylate imatinib (MI) treatment and explore the possible mechanism for apoptosis-inducing effects of imatinib. Methods: K562 cells were cultured with MI at different concentrations. The cells were collected at different time points. Real-time quantitative PCR was used to detect the expression level of SHIP gene. Semi-quantitative reverse transcriptase PCR was used to detect the mRNA transcription of anti-apoptotic gene bcl-2 and pro-apoptotic genes caspase-1, caspase-3 and caspase-9. The cell proliferation was measured by MTT assay. The cell apoptosis was analyzed by Annexin V/PI double staining flow cytometry. Results: MI significantly increased the expression of SHIP gene in a time-and dose-dependent manner. Caspase-9 gene was also up-regulated after MI treatment and had linear correlation with SHIP gene expression. The expression levels of caspase-1, caspase-3 and bcl-2 had no significant changes. MI down-regulated the proliferation and induced the apoptosis of K562 cells. The morphological changes of typical of apoptosis were observed. Conclusion: MI significantly increases the expressions of SHIP gene and caspase-9 gene and induces apoptosis of K562 cells. The mechanism for the apoptosis-inducing effects of imatinib may be associated with the up-regulation of SHIP and caspase-9 gene.

Expressions of cyclin E2 and survivin in acute leukemia and their correlation / 中国实验血液学杂志

Cyclin E2 is present in solid tumors, while its expression and clinical value in acute leukemia is unknown. This study was aimed to investigate the expression of cyclin E2 and survivin gene in bone marrow cells from patients with acute leukemia and their relationship. Reverse transcription polymerase chain reaction was used for detection of the expression of cyclin E2 and survivin mRNA in 84 adult patients with acute leukemia which included 16 cases of relapse, 60 cases of de novo acute leukemia, 8 cases of continuously complete remission, and 20 normal persons as controls. The results showed that (1) positive expression of cyclin E2 (70.24%) in acute leukemia patients was significantly higher than that (0%) in controls, positive expression of survivin (72.62%) in acute leukemia patients was higher than that (30%) in control. (2) the expression of cyclin E2 positively correlated with that of survivin in acute leukemia patients. (3) remission rate in cyclin E2-positive patients (55.81%) was lower than that (88.24%) in cyclin E2-negative patients, the rate of cyclin E2 expression in relapse group was the highest among the three groups; while that in continuously complete remission group was the lowest among the three groups. (4) positive rate of cyclin E2 expression (59.32%) in patients with acute myelocytic leukemia was lower than that (96%) in patients with acute lymphocytic leukemia, no correlation between cyclin E2 expression and white blood cell counts of patients was found. It is concluded that the overexpression of cyclin E2 has been confirmed for the first time to positively correlate with the expression of the survivin in acute leukemia patients, and implicate the poor prognosis. Cyclin E2 may be used as a marker for examination of minimal residual disease.

Expression and significance of X-linked inhibitor of apoptosis protein and its antagonized proteins in acute leukemia / 中国实验血液学杂志

To investigate the expression and significance of X-linked inhibitor of apoptosis protein (XIAP) and XIAP-associated factor 1 (XAF1) in acute leukemia, the expression of XIAP, XAF1, Smac, and HtrA2 mRNA in the bone marrow aspirates from 87 newly diagnosed AL patients, 23 patients in remission, 6 patients in relapse, and 17 normal controls were detected by means of reverse transcriptase polymerase chain reaction (RT-PCR), and their relationship with clinical therapeutic efficiency was analyzed. The results showed that the expression level of XIAP mRNA in newly diagnosed AL patients (0.990 +/- 0.337) was significantly higher than that in normal controls (0.395 +/- 0.148) (P < 0.01); the positive rate and expression level of XAF1 mRNA in newly diagnosed AL patients (56.32%, 0.246 +/- 0.267) were significantly lower than that in normal controls (100%, 0.964 +/- 0.387) (P < 0.01). In 69 out of 87 newly diagnosed AL patients, efficacy remained evaluable. AL patients with high level of XIAP achieved a lower complete remission (CR) rate than patients with low level of XIAP (54.55% and 86.11%, respectively) (P < 0.01). XAF1 positive patients achieved a higher CR rate than XAF1 negative patients (86.84% and 51.61%, respectively) (P < 0.01). It is concluded that the overexpression of XIAP and negativity of XAF1 may be two adverse prognostic factors in AL patients.

Relationship between resistance to chemotherapy and expression of breast cancer resistance protein (BCRP) gene in patients with acute leukemia / 中国实验血液学杂志

In order to investigate the relationship between the expression of breast cancer resistance protein (BCRP) gene and drug resistance in patients with acute leukemia (AL), semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to examine the expression of BCRP mRNA in AL patients and 15 normal subjects. Beta(2)-microglobin (beta(2)-MG) was used as positive reference. BCRP/beta(2)-MG ratio >or= 0.5 was defined as BCRP mRNA positive. The results showed that the positive percentage of BCRP gene expression in newly diagnosed group was 37.6%. The first complete remission rate was 79.3% and 31.6% in BCRP mRNA negative and BCRP mRNA positive patients respectively. The difference was significant (P = 0.001). The expression levels of BCRP mRNA in drug resistance group and drug sensitive group were 0.962 +/- 0.426 and 0.315 +/- 0.296 respectively (P = 0.0001). The expression level of BCRP mRNA in relapsed/refractory group was significantly higher than that in newly diagnosed group (P = 0.0025). The expression level of BCRP gene in normal individuals and long-term survival group was very low and correlated with FAB subtypes. It is concluded that high expression of BCRP mRNA leads to clinical drug resistance and is an unfavorable factor for prognosis of AL patients except acute promyelocytic leukemia.

Blastic natural killer cell leukemia--one case report and review of literature / 中华血液学杂志

<p><b>OBJECTIVE</b>To report a case of blastic natural killer cell leukemia with an aggressive clinical course.</p><p><b>METHODS</b>The characteristics of blastic NK cell leukemia and its treatment were discussed with review of literatures.</p><p><b>RESULTS</b>After combination chemotherapy and spinal cord segmental radiotherapy, the patient entered hematological remission, but the extramedullary lesion remained unchanged.</p><p><b>CONCLUSION</b>Blastic NK cell leukemia has an aggressive clinical course with poor response to treatment and unfavorable prognosis.</p>

Expression of survivin, Fas, bcl-2 and bax in bone marrow cells from acute myeloid leukemia patients and its clinical significance / 中国实验血液学杂志

<p><b>UNLABELLED</b>To study the clinical significance of the expression of antiapoptosis gene, survivin and bcl-2, and proapoptosis gene, Fas and bax, in acute myeloid leukemia (AML), RT-PCR was used to examine the expression of survivin and flow cytometry (FCM) to detect the expression of Fas, bcl-2, bax and bcl-2/bax ratio in 68 cases of AML. The results demonstrated that: (1) The positivity of survivin mRNA expression was significantly higher in AML compared to control (70.6% vs 30%, P < 0.05). (2) The expression of Fas and bcl-2 in AML before treatment was significantly higher than that in control (P < 0.001), but the bax expression did not (P > 0.05). (3) The survivin-positive AML cases showed a significantly lower Fas and higher bcl-2 expression in comparison with survivin-negative ones (P < 0.01 and P < 0.001, respectively), but the bax did not (P > 0.01). (4) Survivin-positive AML cases had a lower CR rate as compared with survivin-negative cases (64.6% vs 90%, P < 0.05). (5) The survivin-positive CR cases showed a decreased expression of Fas and bcl-2 after treatment in comparison with pretreatment expression (P < 0.001), but the bax expression remained unchanged before and after therapy. The survivin-positive NR cases showed a significantly decreased Fas and increased bcl-2 expression as compared with pretreatment expression (P < 0.001). bcl-2/bax ratio was also significantly higher in NR cases.</p><p><b>IN CONCLUSION</b>70.6% AML cases showed positive for survivin expression with a lower CR rate, the survivin-positive AML showed a low Fas with high bcl-2 expression and bcl-2/bax ratio as compared to the survivin-negative cases.</p>