GSK-3ß/ß-catenin pathway plays crucial roles in the regulation of NK cell cytotoxicity against myeloma cells.

The plasma cell malignancy, multiple myeloma (MM), has significantly improved by the application of new drugs and autologous hematopoietic stem cell transplantation. However, MM remains incurable. A number of studies have revealed an anti-MM effect of natural killer (NK) cells; however, their clinical efficacy is limited. Furthermore, glycogen synthase kinase (GSK)-3ß inhibitors show an antitumor function. In this study, we aimed to evaluate the potential roles of a GSK-3ß inhibitor (TWS119) in the regulation of NK cell cytotoxicity against MM. Our results showed that, in the presence of TWS119, the NK cell line, NK-92, and in vitro-expanded primary NK cells exhibited a significantly higher degranulation activity, expression of activating receptors, cellular cytotoxicity, and cytokine secretion when they were exposed to MM cells. Mechanistic studies indicated that TWS119 treatment markedly upregulated RAB27A expression, a key molecule for NK cell degranulation, and induced the colocalization of ß-catenin with NF-κB in the nucleus of NK cells. More importantly, GSK-3ß inhibition combined with the adoptive transfer of TWS119-treated NK-92 cells significantly reduced tumor volume and prolonged the survival time of myeloma-bearing mice. In summary, our novel findings suggest that targeting GSK-3ß through the activation of ß-catenin/NF-κB pathway may be an important approach to improve therapeutic efficacy of NK cell transfusion for MM.

Anaphylaxis caused by pegylated recombinant human granulocyte colony-stimulating factor.

INTRODUCTION: Pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF), is commonly used to prevent and/or treat neutropenia caused by tumor chemotherapy and radiotherapy with reduced clearance, increased plasma half-life, sustained biologic activity, and good safety. PEG-rhG-CSF anaphylaxis was rare. CASE REPORT: A 55-year-old male Non-Hodgkin lymphoma patient appeared with chest tightness, increased heart rate, and decreased blood pressure after taking PEG-rhG-CSF used as a primary treatment for neutropenia caused by chemoradiotherapy. The patient's anaphylaxis is likely due to PEG-rhG-CSF. MANAGEMENT AND OUTCOME: 0.9% sodium chloride 250 mL and dexamethasone sodium phosphate injection 5 mg were carried out. After close observation, the symptoms were improved. Two months later, the patient was readministered with PEG-rhG-CSF and anaphylaxis reoccurred. After the last contact with PEG-rhG-CSF, the patient was prescribed rhG-CSF for many times and did not experience any adverse reactions. DISCUSSION: PEGylated drugs are not free of risk and immune-mediated adverse events are of concern. PEG is a substance capable of triggering an immune response. The mechanism of PEG involved IgE-mediated anaphylaxis and non-IgE-mediated anaphylaxis, and requires further research. PEGylated drugs are not free of risk and immune-mediated adverse events are of concern.

Mesenchymal stem cells significantly improved treatment effects of Linezolid on severe pneumonia in a rabbit model.

The present study aimed to investigate whether co-administration of mesenchymal stromal cells (MSC) and linezolid (LZD) into a rabbit model of methicillin-resistant Staphylococcus aureus (MRSA)-infected pneumonia would bring a synergistic therapeutic effect. Human umbilical cord-derived MSCs (hUMSCs) were isolated and characterized. A rabbit model of pneumonia was constructed by delivering 1 × 1010 CFU MRSA via a bronchoscope into the basal segment of lower lobe of right lung. Through analyzing vital sign, pulmonary auscultation, SpO2, chest imaging, bronchoscopic manifestations, pathology, neutrophil percentage, and inflammatory factors, we verified that a rabbit model of MRSA-induced pneumonia was successfully constructed. Individual treatment with LZD (50 mg/kg for two times/day) resulted in improvement of body weight, chest imaging, bronchoscopic manifestations, histological parameters, and IL-10 concentration in plasma (P<0.01), decreasing pulmonary auscultation, and reduction of IL-8, IL-6, CRP, and TNF-α concentrations in plasma (P<0.01) compared with the pneumonia model group at 48 and 168 h. Compared with LZD group, co-administration of hUMSCs (1 × 106/kg for two times at 6 and 72 h after MRSA instillation) and LZD further increased the body weight (P<0.05). The changes we observed from chest imaging, bronchoscopic manifestations and pathology revealed that co-administration of hUMSCs and LZD reduced lung inflammation more significantly than that of LZD group. The plasma levels of IL-8, IL-6, CRP, and TNF-α in combined group decreased dramatically compared with the LZD group (P<0.05). In conclusion, hUMSCs administration significantly improved therapeutic effects of LZD on pneumonia resulted from MRSA infection in a rabbit model.

Karyotyping of circulating tumor cells for predicting chemotherapeutic sensitivity and efficacy in patients with esophageal cancer.

BACKGROUND: Aneuploidy of chromosome 8 in circulating tumor cells (CTCs) has been reported correlates with therapeutic efficacy and prognosis in patients with advanced gastric cancer. However, it is not clear whether it is also appropriate for other cancer. Therefore, in this study, we evaluate the clinical application aneuploidy of CTCs for esophageal cancer. METHODS: Peripheral blood were collected for karyotyping analysis before and after first 4-cycles chemotherapy from seventy nine patients with newly diagnosed esophageal cancer. Karyotyping of chromosome 8 in CTCs detected by SET-iFISH (Subtraction Enrichment-Immunostaining fluorescence in situ hybridizatio) in those patients were grouped into two categories according to CTC number: triploid group and non-triploid group. Pearson Chi-Square were used to compare the association between different aneuploidy type and chemotherapeutic sensitivity and efficacy. RESULTS: Among the 16 patients with triploid of chromosome 8, 4 patients benefit, and of the 63 patients with non-triploid, 54 patients benefit. Chi-square test analysis found that clinical benefit of non-triploid patients was significantly higher than triploid patients, suggesting non-triploid patients were more sensitive to chemotherapy than triploid patients. After 4-cycles chemotherapy, it is found that chemotherapeutic efficacy was positively correlated with non-triploid proportion. These results suggest that non-triploid proportion could be used as a candidate maker for assessing chemotherapeutic efficacy. CONCLUSIONS: Monitoring aneuploidy of chromosome 8 in CTCs before and after chemotherapy may help predict sensitivity and efficacy of chemotherapy in patients with esophageal cancer.

Infusion of umbilical cord mesenchymal stem cells alleviates symptoms of ankylosing spondylitis.

The current study evaluated 5 patients with ankylosing spondylitis (AS). Patients received intravenous transfusions of umbilical cord mesenchymal stem cells (uMSCs). All therapeutic and adverse responses were assessed and recorded during uMSC therapy. No severe adverse reactions were observed in any of the patients, although a slight transient fever was observed in 3 patients within 2-6 h of intravenous administration of uMSCs. Following treatment, the Bath Ankylosing Spondylitis Disease Activity and Bath Ankylosing Spondylitis Metrology Indices decreased, however the Bath Ankylosing Spondylitis Functional Index increased. The erythrocyte sedimentation rate in 3 patients was reduced and C-reactive protein levels in 1 patient were markedly reduced. The symptoms of AS were alleviated in all patients. The present study indicates that intravenous transfusion of uMSCs is safe and well tolerated by patients and that it effectively alleviates disease activity and clinical symptoms. In the future, a larger cohort of patients with AS should be recruited to enable the systemic evaluation of uMSC therapy.

Clinical presentation of hemophagocytic lymphohistiocytosis in adults is less typical than in children.

OBJECTIVE: Hemophagocytic lymphohistiocytosis in adults is largely underdiagnosed. To improve the rate and accuracy of diagnosis in adults, the clinical and laboratory characteristics of hemophagocytic lymphohistiocytosis were analyzed in and compared between adults and children in a Chinese cohort. METHOD: Data from 50 hemophagocytic lymphohistiocytosis patients, including 34 adults and 16 children who fulfilled the 2004 hemophagocytic lymphohistiocytosis diagnostic criteria, were collected and analyzed. RESULTS: 1. Etiological factors: The proportion of Epstein-Barr virus infection was lower in adults compared with children, whereas fungal infection and natural killer/T cell lymphoma were more frequent in adults (P<0.05). 2. Clinical manifestations and laboratory findings: Over 90% of adults and pediatric patients presented with fever, thrombocytopenia and high serum ferritin levels. However, in adults, the proportions of hepatomegaly, splenomegaly and jaundice were much lower (P<0.01) than in children, and serous cavity effusion was more frequent in adult patients (P<0.05). More children had hemoglobin <90 g/L, total bilirubin >19 mmol/L and lactate dehydrogenase >500 U/L compared with adults (P<0.05). 3. The time interval from the onset of symptoms to clinical diagnosis was significantly shorter in pediatric patients than in adults (P<0.05). CONCLUSIONS: Certain clinical features were different between the two groups. The less characteristic clinical presentation of hemophagocytic lymphohistiocytosis in adults may make the disease more difficult to diagnose. Our findings suggest that hemophagocytic lymphohistiocytosis should be considered when an adult patient presents with the above-mentioned symptoms.

Clinical presentation of hemophagocytic lymphohistiocytosis in adults is less typical than in children

OBJECTIVE: Hemophagocytic lymphohistiocytosis in adults is largely underdiagnosed. To improve the rate and accuracy of diagnosis in adults, the clinical and laboratory characteristics of hemophagocytic lymphohistiocytosis were analyzed in and compared between adults and children in a Chinese cohort. METHOD: Data from 50 hemophagocytic lymphohistiocytosis patients, including 34 adults and 16 children who fulfilled the 2004 hemophagocytic lymphohistiocytosis diagnostic criteria, were collected and analyzed. RESULTS: 1. Etiological factors: The proportion of Epstein-Barr virus infection was lower in adults compared with children, whereas fungal infection and natural killer/T cell lymphoma were more frequent in adults (P<0.05). 2. Clinical manifestations and laboratory findings: Over 90% of adults and pediatric patients presented with fever, thrombocytopenia and high serum ferritin levels. However, in adults, the proportions of hepatomegaly, splenomegaly and jaundice were much lower (P<0.01) than in children, and serous cavity effusion was more frequent in adult patients (P<0.05). More children had hemoglobin <90 g/L, total bilirubin >19 mmol/L and lactate dehydrogenase >500 U/L compared with adults (P<0.05). 3. The time interval from the onset of symptoms to clinical diagnosis was significantly shorter in pediatric patients than in adults (P<0.05). CONCLUSIONS: Certain clinical features were different between the two groups. The less characteristic clinical presentation of hemophagocytic lymphohistiocytosis in adults may make the disease more difficult to diagnose. Our findings suggest that hemophagocytic lymphohistiocytosis should be considered when an adult patient presents with the above-mentioned symptoms.

Predictive value of microRNAs as novel biomarkers in detection of lymphoma.

MicroRNAs (miRNAs) have attracted many attentions in lymphoma diagnostic research. The inconsistence of diagnostic performance in these existed literatures leading us to conduct this meta-analysis. In order to have a scientific and reliable study, all related articles were screened from Medline, Embase, CNKI and other databases. The sensitivity and specificity of each involved research were used to plot the summary receiver operator characteristic (SROC) curve and calculate the area under the curve (AUC). The QUADAS-2 tool was applied to estimate the quality of included studies. In addition, Deeks' funnel plot asymmetry test was performed to estimate publication bias. Overall, 14 studies from 6 articles were included to evaluate the whole test performance. The overall pooled results were as follows: sensitivity was 0.91 (95% CI: 0.83-0.95), specificity was 0.84 (95% CI: 0.75-0.90), the AUC was 0.93 (95% CI: 0.91-0.95), positive likelihood ratio-PLR was 5.5 (95% CI: 3.5-8.8), negative likelihood ratio-NLR was 0.11 (95% CI: 0.06-0.21), and diagnostic odds ratio-DOR was 50 (95% CI: 19-128). In summary, results from meta-analysis showed that miRNAs analysis might significantly increase the diagnostic accuracy of lymphoma. Further massive prospective studies still needed to validate our conclusion before clinical application.

CIP2A is overexpressed and involved in the pathogenesis of chronic myelocytic leukemia by interacting with breakpoint cluster region-Abelson leukemia virus.

To detect the expression of cancerous inhibitor of phosphatase 2A (CIP2A) in chronic myelocytic leukemia (CML) and investigate the mechanism underlying CIP2A knockdown-mediated cell proliferation and apoptosis as well as the interaction of CIP2A with breakpoint cluster region-Abelson leukemia virus (BCR-ABL). CIP2A mRNA and protein expression in chronic myelocytic leukemia-chronic (CML-CP) patients and healthy controls were determined by RT-PCR and Western blot. In vivo, c-Myc expression, PP2A activity, cell proliferation, and apoptosis of CML cells were detected with CIP2A depletion. In addition, the relationship among CIP2A, BCR-ABL, and tyrosine phosphatase SHP-1 was explored by depleting/overexpressing CIP2A or inhibiting BCR-ABL. The level of CIP2A mRNA was higher in CML-CP patients than healthy controls (56/74, 75.7 % vs. 1/35, 2.9 %, P < 0.001), and CIP2A protein was overexpressed in corresponding specimens. CIP2A knockdown by siRNA reduced the level of c-Myc protein and clonogenic formation, inhibited the activity of PP2A, K562 cell proliferation, and promoted cell apoptosis. Suppressing BCR-ABL by imatinib mesylate (IM) significantly decreased CIP2A expression. CIP2A knockdown decreased BCR-ABL but increased SHP-1 expression, and CIP2A overexpression had the reverse effect. CIP2A is overexpressed in CML-CP patients, and its expression may promote CML pathogenesis. CIP2A and BCR-ABL can regulate each other in a positive feedback loop. CIP2A may be a useful therapeutic target in CML-CP, particularly in patients with IM resistance. However, further studies are needed to validate the interaction between CIP2A and BCR-ABL using other tyrosine kinase inhibitors than IM.

Umbilical cord mesenchymal stem cell transfusion ameliorated hyperglycemia in patients with type 2 diabetes mellitus.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a serious threat to human health and remains incurable. Insulin deficiency seems to be attributed to the progressive failure of pancreatic islet ß-cells and immune cells such as T cells mediated cytotoxicity may be involved in the loss of pancreatic islet ß-cells in T2DM. Targeting on the immune system to maintain functional activity of pancreatic islet ß-cells could be an attractive way to treat T2DM. Mesenchymal stem cells (MSCs) exert potent capacity of immunomodulation. MSCs have been successfully applied for the treatment of several types of autoimmune diseases. So, the aim of this study is to evaluate the safety and potential therapeutic effects of UMSC on T2DM. METHODS: UMSCs were separated, expanded, and identified on the basis of the previous description. 18 patients of T2DM were recruited according to our experimental protocol. UMSC was intravenously transfused three times. All patients were followed up in the first, third, and sixth month. Age, gender, diabetes duration and medications as well as weight, height, and BMI were recorded. Fasting plasma glucose (FPG), postprandial blood glucose (PBG), HbA1c, C-peptide, and subsets of T cells were measured. All adverse reactions were carefully documented. Effective criteria were made and data was analyzed using SPSS 19.0 software. RESULTS: UMSCs were successful obtained. Baseline clinical characteristics between the efficacy and inefficacy groups were not statistically different (p > 0.05). FBG and PBG of the patients in efficacy group were significantly reduced (p < 0.05) after UMSC transfusion. Plasma C-peptide levels and regulatory T (Treg) cell number in the efficacy group were numerically higher after UMSC transfusion; however, the difference of both parameters did not reach significance (p > 0.05). During the treatment course only 4 out of 18 patients (22.2%) had slight transient fever. Up to 6 months after UMSC transfusion, all patients continued to have a feeling of well-being and were physically more active. CONCLUSIONS: UMSC transfusion is safe and well tolerated, effectively alleviates blood glucose, and increases the generation of C-peptide levels and Tregs in a subgroup of T2DM patients. This pilot study provides fundamental data for further study of UMSC transfusion on control of blood glucose as well as morbidity of T2DM in a larger cohort.

Bortezomib and IL-12 produce synergetic anti-multiple myeloma effects with reduced toxicity to natural killer cells.

The aim of this study was to examine the hypothesis that a combination of proteasome inhibition by bortezomib and immune therapy with interleukin-12 (IL-12) can produce enhanced antitumor efficacy relative to the effects of either of these agents alone. A mouse xenograft model of myeloma was developed. The mice were randomly divided into saline control (NS), IL-12 (0.4 µg/animal; intraperitoneal), bortezomib (0.75 mg/kg; intravenous), and bortezomib+IL-12 groups. Effects of treatments on tumor growth were assessed by before and after treatment comparisons and group comparisons. The effects of various treatments on the number of peripheral blood lymphocytes and natural killer (NK) cells were assessed by complete blood count and flow cytometry analysis. The cell-killing function of NK cells in splenocytes was evaluated using the lactate dehydrogenase release assay. IL-12 treatment alone produced a mild decrease in tumor volume compared with control (P>0.05). Bortezomib alone resulted in substantial inhibition of tumor growth at varying time points, reaching ~65 and ~60% reduction in tumor volume after 15 and 21 days of therapy, respectively. At the same time points, the combination therapy produced ~75 and ~84% decreases in tumor growth, respectively, which were significantly greater than the reduction produced by bortezomib monotherapy. Tumors resumed growth upon termination of bortezomib treatment at 2 weeks, although the tumor volume was still significantly smaller than that in the time-matched NS and IL-12 animals. This rebound of tumor growth was completely prevented with the combination therapy, and tumor volume continued to decrease throughout the time course. The percentage and total number of NK cells were significantly decreased after bortezomib monotherapy and combination therapy; however, they remained unaltered after IL-12 treatment compared with no treatment. Further, combination therapy significantly restored the bortezomib-induced functional impairment of the cell-killing capability of NK cells, relative to bortezomib alone. We conclude that the bortezomib-IL-12 combination therapy offers superior antitumor efficacy over monotherapy with either bortezomib or IL-12 in a mouse model of myeloma. Restoration of bortezomib-induced functional impairment of NK cells by IL-12 may be a mechanism for the synergetic effects of the two agents. Therefore, a combination of the two agents may represent a more rational therapeutic approach for myeloma.

Characterization of Th1- and Th2-associated chemokine receptor expression in spleens of patients with immune thrombocytopenia.

PURPOSE: In view of the numerous clinical observations and laboratory studies that suggest a critical role for the spleen in immune thrombocytopenia (ITP) pathophysiology, we aimed to characterize Th1-associated chemokine receptors CXCR3 and CCR5 and Th2-associated chemokine receptor CCR3 in spleens of ITP patients and assess the significance of their differential expression in the clinical setting. METHODS: The histopathology of spleens was observed using hematoxylin-eosin staining (HE), and the positive rate of CXCR3, CCR5 and CCR3 expression in spleens of 24 ITP patients and 12 patients with traumatic splenic rupture as normal controls was detected by immunohistochemistry using the SP method. CXCR3, CCR5 and CCR3 protein expression was analyzed by Western blot and mRNA levels were investigated by real-time polymerase chain reaction (RT-PCR). RESULTS: Reactive hyperplasia could be seen in follicles of the white pulp, the germinal central zone was enlarged and the marginal zone was thickened, the central arteries were thickened and fibrotic, and the density of the capillary vessel was increased in ITP patients. ITP group displayed a higher rate of expression of Th1-associated chemokine receptors CXCR3 and CCR5 (83.3% vs. 75%, 100% vs. 83.3%) but lower rate of expression of Th2-associated chemokine receptor CCR3 (50% vs. 66.7%) compared with the controls (P < 0.05, respectively). Western blot analysis revealed that CXCR3 and CCR5 protein expression was significantly increased in ITP patients while CCR3 was significantly reduced (P < 0.05, respectively). Meanwhile, ITP patients displayed increased mRNA levels of CXCR3 and CCR5 but decreased gene expression of CCR3 (P < 0.05, respectively). CONCLUSION: The data suggested that the abnormal expression of Th1/Th2 chemokine receptors may participate in splenic immune disorder in patients with ITP. Using corresponding inhibitors may inhibit Th1-dominant expression and mitigate the progress of the disease.

[Expression of CXCR3 and CCR5 chemokine receptor in spleens of patients with primary immune thrombocytopenia].

OBJECTIVE: To study CXCR3 and CCR5 chemokine receptor expression in spleens of patients with primary immune thrombocytopenia (ITP) and its clinical significance. METHODS: The splenectomy specimens from 10 ITP patients (ITP group) and 8 patients with traumatic splenic rupture (normal control group) were studied. Immunohistochemistry (IHC) was used to study the positive rate of CXCR3 and CCR5. Western blot was performed to detect CXCR3 and CCR5 protein expression, while real-time polymerase chain reaction (RT-PCR) was conducted to analyze their mRNA expression. RESULTS: The positive rate of CXCR3 and CCR5 were both higher in ITP group (90% and 100%, respectively) than those in control group (75% and 87.5%, respectively)(P < 0.05). The differences were statistically significant (P < 0.05). Protein and mRNA level of CXCR3 in ITP group were 3.0 and 3.5 times as high as those in control group, respectively. Those of CCR5 in ITP group were 1.2 and 1.7 times as high as those in control group, respectively. CONCLUSION: High expression of CXCR3 and CCR5 may play a part in the splenic immune disorders in patients with ITP.

[In vitro activation of bone marrow natural killer T cells of aplastic anemia patients].

OBJECTIVE: To investigate the quantitative and qualitative changes of TCRVα24(+)Vß11(+) natural killer T (NKT) cells from bone marrow (BM) of aplastic anemia (AA) after in vitro stimulation of α-galactosylceramide (α-Galcer). METHODS: NKT cells in the bone marrow mononuclear cells (BMMNCs) from either AA patients or healthy controls were enumerated with flow cytometry. BMMNCs were cultured in RPMI1640 medium supplemented with either α-Galcer and rhIL-2 or α-Galcer, rhIL-2 and rhG-CSF. The proliferative capacity of NKT cells was determined by NKT cell numbers before and after in vitro culture. Expression of intracellular IFNγ and IL-4 in activated NKT cells was analyzed with flow cytometry. RESULTS: In AA group, the percentage of NKT cells in BMMNCs was (0.19 ± 0.09)%. Addition of rhG-CSF into the α-Galcer/rhIL-2 culture medium resulted in significantly reduced expansion of NKT cells (67.45 ± 29.42-fold vs 79.91 ± 40.56 fold, P < 0.05). Meanwhile, addition of rhG-CSF reduced IFNγ positive NKT cells \[(37.45 ± 7.89)% vs (62.31 ± 14.67)%, P < 0.01\] and increased IL-4 positive NKT cells \[(55.11 ± 12.13)% vs (27.03 ± 9.88)%, P < 0.01\]. In healthy control group, the percentage of NKT cells in BMMNCs was (0.25 ± 0.12)%. Addition of rhG-CSF into the α-Galcer/rhIL-2 culture medium also significantly reduced expansion of NKT cells (97.91 ± 53.22-fold vs 119.58 ± 60.49-fold, P < 0.05), reduced IFNγ positive NKT cells \[(28.65 ± 10.63)% vs (50.87 ± 12.66)%, P < 0.01\], and increased IL-4 positive NKT cells \[(66.53 ± 14.96)% vs (31.11 ± 10.07)%, P < 0.01\]. CONCLUSION: Compared to those from healthy controls, BMMNCs from AA patiants have a reduced fraction of NKT cells, which possesses a decreased potential to expand in vitro in response to α-Galcer stimulation, and produce more IFNγ(+) NKT1 cells. rhG-CSF, in combination with α-Galcer, confers polarization of NKT cells towards IL-4(+) NKT2 subpopulation.

[Changes of gene expression profile in homoharringtonine-induced leukemia multi-drug resistant cell line K562/HHT].

OBJECTIVE: To study the resistant related molecules of human leukemia drug resistant K562 cells (K562/HHT) induced by homoharringtonine (HHT). METHODS: Gene expression profiles on K562/HHT, K562 and K562/HHT/RU486 (K562/HHT reversed by RU486) cells were detected by DNA microarray. The bone marrow tyrosine kinase gene in chromosome X (BMX) which changed dynamically among the three cells was confirmed by RT-PCR and Western blot. Then, BMX was transfected into K562 and K562/HHT cells, and the changes of daunorubicin (DNR) concentrations in these two cells were observed for BMX overexpression. RESULTS: As compared with K562, there were changes in 117 gene expressions in K562/HHT, 57 of which were up-regulated and 60 down-regulated. The mdrl gene was significantly up-regulated. When compared with K562/HHT, 50 significantly differently expressed genes were screened out in the K562/HHT/RU486 cells, of which up- and down-regulated genes were 13 and 37 respectively. These genes involved in drug resistance, cell signaling, cell differentiation, cell proliferation, transcription regulator, ion transport and so on. Four genes [NM-001721 (BMX), NM-031459 (SESN2), NM-033642 (FGF13) and AL-049309 (SFRS12)] expressed significantly differently in the two group cells, BMX gene expression was higher in K562/HHT, than in K562, but lower than in K562/HHT/RU486 as confirmed by RT-PCR and Western blot. After the plasmid pCI-neo-BMX was transfected into K562 and K562/HHT cells, DNR concentration was significantly lower (79.28 +/- 4.04, 29.84 +/- 2.67) than those before transfection (158.52 +/- 8.08, 58.58 +/- 6.53). CONCLUSION: BMX is associated with multi-drug resistance of K562/HHT cell line.

[Expression of specific antibodies against platelet glycoproteins in patients with mds and its significance].

The aim of this study was to find platelet specific autoantibodies against glycoproteins in myelodysplastic syndrome (MDS) and to explore its role in pathogenesis of MDS. The plasma autoantibodies against GP IIb/IIIa and GP Ib/IX were measured by using a modified monoclonal antibody specific immobolization platelet antigens assay (MAIPA). Absorbance greater than mean value plus tripled standard deviation recorded from the normal controls were regarded as positive. The results indicated that the total positive rate in patients with MDS was 16.67% (5/30), the total positive rate in patients with ITP was 46.67% (14/30), the difference between MDS group and ITP group was significant (P < 0.05). It is concluded that partial patients with MDS have plasma specific autoantibodies against platelet GP II b/III a and GP Ib/IX, indicating correlation of thrombocytopenia of patients with immune factors and the autoantibody-mediated platelet destruction may be involved in the pathogenesis of MDS. It provides a new basis for immunosuppression therapy for MDS.