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Leukemia & lymphoma 12/2012; · 2.40 Impact Factor
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Xin Li, Xiaoqing Li,
Wei Xie,
Yanjie Hu,
Juan Li,
Wen Du,
Wei Liu,
Hongrui Li,
Xiangjun Chen,
Lannan Zhang,
Junfeng Wang,
Shiang Huang
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ABSTRACT: Diagnostic cytogenetic and molecular analysis is recognized as the most valuable prognostic factor in acute myeloid leukemia (AML). Among 2516 consecutive Chinese patients with de novo AML, 2308 patients had successful cytogenetic results including 61 subclasses of cytogenetic abnormalities and 27 kinds of additional cytogenetic abnormalities. The incidence of t(15;17)(q22;q12) was highest (16.7% of 2308 patients), followed by t(8;21)(q22;q22) (15.1%), trisomy 8 (5.5%), loss of Y (4.5%), trisomy 21 (2.4%), inv(16)(p13q22) or t(16;16)(p13;q22) (2.1%), etc. In comparison to children, adults had higher incidence of normal karyotype (41.5% vs. 29.1%, P<0.001) and lower incidences of t(8;21)(q22;q22) (13.4% vs. 25.8%, P<0.001), t(9;11)(p22;q23) (0.2% vs. 1.2%, P=0.001) and other 11q23 rearrangements (1.0% vs. 3.4%, P<0.001). Among 349 AML patients with t(8;21)(q22;q22), 310 (35.5%) were found in 873 patients with M2. The t(15;17)(q22;q12) was exclusively observed in 386 (71.0%) of 544 patients with M3. In 48 AML patients with inv(16)(p13q22) or t(16;16)(p13;q22), 42 (15.2%) were detected in 276 patients with M4. Our study displayed the cytogenetic characteristics in a large series of Chinese patients with de novo AML. Our results revealed the similarities and differences of cytogenetic abnormalities existing between Chinese and western AML patients.
Blood Cells Molecules and Diseases 06/2012; 49(2):107-13. · 2.35 Impact Factor
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ABSTRACT: The human ether-a-go-go-related (herg) gene encoding K+ channels (HERG) belongs to an evolutionarily conserved multigene family of voltage activated K+ channels. The functional properties of HERG K+ channels are complex and their contribution to the repolarization of the cardiac action potential are well understood. Recent
studies revealed that HERG K+ channels are preferentially expressed in different histogenesis of tumor cells. Leukemia is a cancer that originates in the
bone marrow hematopoietic stem cells (HSCs). Leukemia stem cells (LSCs) are critical in the perpetuation of the disease. A
better understanding of LSCs and molecular biology will allow the design of more effective therapies. We report in this study
that herg was expressed in CD34+/CD38−/CD123high LSCs but not expressed in normal bone marrow CD34+/CD38− HSCs. In addtion, herg is also expressed in leukemia cell lines K562 and HL-60 and almost all the primary leukemia cells
whereas not in the normal bone marrow cells. In addition, the expression of herg mRNA was not associated with the clinical
and cytogenetic feature of leukemia. Moreover, HERG K+ channels can regulate leukemia cells proliferation and cell cycle. These data provide evidence for the oncogenic potential
of HERG K+ channels and it may be a novel, potential pharmacological target for leukemia therapy in the future.
International Journal of Hematology 04/2012; 87(4):387-392. · 1.27 Impact Factor
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ABSTRACT: Direct electrochemistry of hemoglobin (Hb) entrapped in the dextran (De) film on the surface of a room temperature ionic liquid
1-butyl-3-methylimidazolium hexafluorophosphate (BMIMPF6) modified carbon paste electrode (CILE) has been investigated. UV-Vis and FT-IR spectroscopy showed that Hb retained its
native structure in the De film. Scanning electron microscopy (SEM) indicated an uniform film was formed on the electrode
surface. Cyclic voltammetric experiments indicated that the electron transfer efficiency between Hb and the electrode was
greatly improved due to the presence of the De film and ionic liquid, which provided a biocompatible and higher conductive
interface. A pair of well-defined and quasi-reversible redox peak was obtained with the anodic and cathodic peaks located
at −0·195 V and −0·355 V in pH 7·0 phosphate buffer solution, respectively. The electrochemical parameters were calculated
by investigating the relationship of the peak potential with the scan rate. The fabricated De/Hb/CILE showed good electrocatalytic
ability to the reduction of H2O2 with the linear concentration range from 4·0 × 10−6 to 1·5 × 10−5 mol/L and the apparent Michaelis-Menten constant (K
M
app) for the electrocatalytic reaction was calculated as 0·17 µM.
KeywordsHemoglobin-dextran-direct electrochemistry-ionic liquid-cyclic voltammetry
Journal of Chemical Sciences 04/2012; 122(2):271-278. · 1.18 Impact Factor
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Xin Li,
Juan Li,
Yanjie Hu,
Wei Xie,
Wen Du,
Wei Liu, Xiaoqing Li,
Xiangjun Chen,
Hongrui Li,
Junfeng Wang,
Lannan Zhang,
Shiang Huang
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ABSTRACT: Cytogenetics and molecular cytogenetics of 1466 Chinese patients with de novo acute lymphoblastic leukemia (ALL) were studied. Cytogenetic results were available in 1175 patients. Cross-correlations of 23 subclasses of cytogenetic abnormalities were described. Childhood cases had higher incidences of normal karyotype, t(1;19), +8, 12q-, +21, +22 and high hyperdiploidy with 51-65 chromosomes, and lower incidences of t(9;22) and -5/5q- than adult ones (all p<0.05). Relationships of cytogenetic subclasses with immunophenotyping subgroups of ALL were studied. Our study presents the cytogenetic characteristics of a large series of Chinese ALL patients.
Leukemia research 01/2012; 36(6):720-6. · 2.36 Impact Factor
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ABSTRACT: The signaling pathways associated with the Toll-like receptors (TLRs) and nuclear factor-kappaB (NF-κB) are essential to pro-inflammatory cytokine and chemokine expression, as well as initiating innate epithelial immune responses. The TLR/NF-κB signaling pathways must be stringently controlled through an intricate network of positive and negative regulatory elements. MicroRNAs (miRNAs) are non-coding small RNAs that regulate the stability and/or translation of protein-coding mRNAs. Herein we report that miR-16 promotes NF-κB-regulated transactivation of the IL-8 gene by suppression of the silencing mediator for retinoid and thyroid hormone receptor (SMRT). LPS stimulation activated miR-16 gene transcription in human monocytes (U937) and biliary epithelial cells (H69) through MAPK-dependent mechanisms. Transfection of cells with the miR-16 precursor promoted LPS-induced production of IL-8, IL-6, and IL-1α, without a significant effect on their RNA stability. Instead, an increase in NF-κB-regulated transactivation of the IL-8 gene was confirmed in cells following transfection of miR-16 precursor. Importantly, miR-16 targeted the 3'-untranslated region of SMRT and caused translational suppression of SMRT. LPS decreased SMRT expression via upregulation of miR-16. Moreover, functional manipulation of SMRT altered NF-κB-regulated transactivation of LPS-induced IL-8 expression. These data suggest that miR-16 targets SMRT and modulates NF-κB-regulated transactivation of the IL-8 gene.
PLoS ONE 01/2012; 7(1):e30772. · 4.09 Impact Factor
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ABSTRACT: The tyrosine kinase domain (TKD) mutations of receptor tyrosine kinase C-KIT are associated with a poor prognosis in acute myeloid leukemia (AML). However, the underlying mechanisms are not fully understood. We found the activity of protein phosphatase 2A (PP2A), a human tumor suppressor whose dysfunction contributes to malignant cell behavior, was significantly decreased in AML subgroups harboring C-KIT/D816V and AML cell line Kasumi-1 bearing C-KIT/N822K mutation. Primary AML cells and various AML cell lines were treated with PP2A activator FTY720. FTY720 showed a toxic effect in all leukemic cells, especially for cells harboring C-KIT/TKD mutation. Furthermore, FTY720-induced toxicity in AML leukemic cells was mediated by restoration of PP2A activity, via down-regulation of PP2A inhibitor SET, dephosporylation of PP2A-C(TYR307), and up-regulation of relevant PP2A subunit A and B55α. Our research indicates that the decreased PP2A activity in AML harboring C-KIT/TKD mutation may make the restoration of PP2A activity a novel therapy for AML patients with C-KIT/TKD mutation.
Journal of Cellular Biochemistry 11/2011; 113(4):1314-22. · 2.87 Impact Factor
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ABSTRACT: The BCR-ABL tyrosine kinase has been implicated in the dysregulation of oncogenes and tumor suppressor genes involved in chronic myelogenous leukemia (CML). Suppressor of activator protein-1, regulated by interferon (SARI), is a recently identified tumor suppressor gene whose expression has been reported to be suppressed in several malignant neoplasms. However, the expression of SARI in leukemia and the underlying regulatory mechanism remain elusive. In this study, we demonstrated that SARI mRNA expression was low in CML patients. In vitro, BCR-ABL kinase inhibitor imatinib mesylate or siRNA specific to BCR-ABL upregulated SARI mRNA expression in human leukemia cells. In addition, JAK/STAT signaling inhibitor AG490 and RAS/MAPK signaling inhibitor PD98059 upregulated SARI mRNA expression, but PI3K/AKT pathway inhibitor LY294002 had no such effect. Functionally, silencing of SARI in CML-derived cell line K562 partially decreased imatinib mesylate-induced apoptosis. Taken together, these data demonstrate that SARI mRNA expression is suppressed by BCR-ABL through the downstream signaling pathways, suggesting SARI as a potential therapeutic target in CML.
Tumor Biology 09/2011; 32(6):1191-7. · 1.94 Impact Factor
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ABSTRACT: Ikaros is a zinc-finger transcription factor that plays an important role in the differentiation and proliferation of lymphocytes. Dominant-negative Ikaros isoform 6 (Ik6), one of its common subtypes, is overexpressed in leukemia patients and is associated with unfavorable prognosis in childhood B-cell progenitor acute lymphoblastic leukemia (ALL). This study was to identify specific isoforms, especially Ik6, in Chinese pediatric patients with ALL. The mRNA expression of Ikaros was detected in 88 children with previously untreated ALL by nested reverse transcription-polymerase chain reaction (RT-PCR). Sequencing of the PCR products was performed to identify specific isoforms. The expression of fusion genes was determined by using multiplex RT-PCR. The functional isoforms Ik1, Ik2/3, and dominant negative isoforms Ik4, 6, 8, 9, 10 identified by nested RT-PCR were further confirmed by sequence analysis. In the 88 cases, the Ik6 was found to be overexpressed in 8 of 70 cases of B-lineage ALL and in 1 of 18 cases of T-lineage ALL patients. Among Ik6 B-lineage ALL patients, 3 had expression of BCR/ABL fusion gene and 1 had HOX11 expression. Ik6 overexpression was independent of age, white blood cell count at diagnosis, risk group, and expression of the fusion genes currently measured in China except BCR/ABL (P<0.01). And it was strongly associated with elevated levels of minimal residual disease at day 28 (P<0.01). Ik6 can be included as a high-risk factor at diagnosis. In developing countries with limited resources, it can be economically detected by nested RT-PCR.
Journal of Pediatric Hematology/Oncology 08/2011; 33(6):429-32. · 1.16 Impact Factor
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ABSTRACT: The relationship between the expression of vascular endothelial growth factor (VEGF) and microvascular density (MVD) marked by CD105 (CD105-MVD), and that between CD105-MVD and the clinicopathological characteristics of primary pterygium were investigated. The streptavidin-biotin complex (SABC) immunohistochemical staining in paraffin-embedded tissues was used to detect the expression of VEGF in 23 cases of primary pterygia and 7 normal conjunctival specimens. The antibody against CD105 was used to display vascular endothelial cells, and MVD was examined by counting the CD105-positive vascular endothelial cells. The correlations of VEGF and CD105-MVD, and those of CD105-MVD and clinicopathological data were analyzed by using SPSS 12.0. The expression of VEGF was significantly increased in epithelia (P=0.000), endothelia and stroma cells (P=0.005) in primary pterygia as compared with normal conjunctivae. The CD105-MVD in pterygia (mean 19.22±6.68) was higher than that in normal conjunctivae (mean 4.00±2.15, P=0.000). MVD in pterygia was significantly associated with the Tan classification (P=0.000) and the VEGF expression level in the stroma (P=0.020), but not with sex (P=0.61), age (P=0.150) or the VEGF expression level in the epithelia (P=0.518). Our results suggest that over-expression of VEGF and high CD105-MVD in primary pterygium may contribute to the progression by increasing angiogenesis and growth of primary pterygium.
Journal of Huazhong University of Science and Technology 08/2011; 31(4):560-4. · 0.38 Impact Factor
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ABSTRACT: Immunophenotyping is one of the independent prognostic factors in acute myeloid leukemia (AML). Relevance of immunophenotypes to prognostic subgroups of age, white blood cells (WBC), platelet count, and cytogenetics in de novo AML was comprehensively investigated in this study for the first time. Human leukocyte antigen (HLA)-DR and CD14 expression associated with the elderly, highest WBC count, and unfavorable-risk cytogenetics; CD4, CD7, and CD11b expression correlated with highest WBC count and unfavorable-risk cytogenetics; CD64 expression was associated with higher WBC count while that of CD13 was associated with lower platelet count; CD22, CD34, CD123, and terminal deoxynucleotidyl transferase (TdT) expression correlated with unfavorable-risk cytogenetics; CD5 expression was associated with normal platelet count while that of CD19 was associated with children and favorable-risk cytogenetics; CD117 expression was associated with low WBC and lower platelet counts; myeloperoxidase (MPO) expression correlated with lower platelet count; and MPO and glycophorin A (Gly-A) expression was associated with lower WBC count and favorable-risk cytogenetics. The results of the relevance analysis revealed the distribution characteristics of antigen expression in different AML prognostic subgroups. The majority of antigens associated with good or poor prognostic subgroups were in accordance with the previous reports of correlation of expression of these antigens with prognosis. Antigens associated with good (or poor) prognostic subgroups were defined as good (or poor)-risk antigens.
Apmis 01/2011; 119(1):76-84. · 1.99 Impact Factor
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ABSTRACT: Multiparameter flow cytometry (MFC) plays a vital role in the detection of minimal residual disease (MRD) and diagnosis of relapse in acute leukemia. However, application of a limited panel of antibodies in MFC leads to high rates of false-negative and false-positive results. Thirteen patients with acute lymphoblastic leukemia (ALL) and 12 patients with acute myeloid leukemia (AML) were immunophenotyped by MFC at diagnosis and at relapse using a comprehensive panel of monoclonal antibodies (McAbs) to 27 antigens and CD45/SSC gating. In 23 of 25 patients (92.3%), changes in at least one of progenitor-associated, myeloid and lymphoid antigens between diagnosis and relapse were observed. Antigen changes were observed in 92 of 239 antigens (38.5%) expressed in 25 patients, in 49 of 117 antigens (41.9%) expressed in 13 ALL patients, and in 43 of 122 antigens (35.2%) expressed in 12 AML patients. Phenotypic changes were characterized by the expression of cross-lineage antigens. The intralineage change was observed in the majority of patients. However, myeloid lineage shift was identified by MFC in two patients with T-ALL. Multiple panels of three or more McAbs are likely to be required in the monitoring of MRD and diagnosis of relapse in acute leukemia by MFC.
Apmis 05/2010; 118(5):353-9. · 1.99 Impact Factor
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British Journal of Haematology 03/2010; 150(2):242-4. · 4.94 Impact Factor
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ABSTRACT: Deregulation of insulin-like growth factor-1 receptor (IGF-1R) is closely associated with malignant transformation and tumor cell survival in various cancers. We found that IGF-1R expression level in leukemia cells positively correlated with the percentage of blast in bone marrow from de novo acute myeloid leukemia (AML) patients. Moreover, we showed that NVP-ADW742, a novel small weight molecular inhibitor of IGF-IR, could induce apoptosis in both HL-60 cell line and primary AML blasts. However, no significant alteration of cell cycle was observed in HL-60 cells. Further studies revealed that NVP-ADW742 induced Akt dephosphorylation, which might subsequently induce p38 phosphorylation and decrease antiapoptotic protein Bcl-2 expression in HL-60 cells. Finally, we demonstrated that NVP-ADW742 could synergize with Ara-C to induce the kill in a subset of drug-resistant AML specimens. We suggested that IGF-lR targeting might be therapeutically beneficial for some AML patients.
Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics 01/2010; 19(1):35-43. · 1.30 Impact Factor
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ABSTRACT: A new electrochemical biosensor was constructed by immobilization of hemoglobin (Hb) on a DNA modified carbon ionic liquid electrode (CILE), which was prepared by using 1-ethyl-3-methylimidazolium tetrafluoroborate (EMIMBF4) as the modifier. UV-vis absorption spectroscopic result indicated that Hb remained its native conformation in the composite film. The fabricated Nafion/Hb/DNA/CILE was characterized by scanning electron microscopy (SEM), electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). A pair of well-defined redox peaks was obtained on the modified electrode, indicated that the Nafion and DNA composite film provided an excellent biocompatible microenvironment for keeping the native structure of Hb and promoting the direct electron transfer rate of Hb with the basal electrode. The electrochemical parameters of Hb in the composite film were further calculated with the results of the charge transfer coefficient () and the apparent heterogeneous electron transfer rate constant (ks) as 0.41 and 0.31 s−1. The proposed electrochemical biosensor showed good electrocatalytic response to the reduction of trichloroacetic acid (TCA), H2O2, NO and the apparent Michaelis–Menten constant (KMapp) for the electrocatalytic reaction was calculated, respectively.
Electroanalysis 10/2009; 21(22):2454 - 2460. · 2.87 Impact Factor
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European Journal Of Haematology 10/2009; 84(1):87-8. · 2.61 Impact Factor
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Leukemia research 10/2009; 34(1):e30-1. · 2.36 Impact Factor
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ABSTRACT: Aberrant epigenetic regulation has recently been implicated in the downregulation of tumour suppressor microRNAs (miRNAs). Histone modification and DNA methylation can have different roles in gene silencing in cancer. To investigate whether histone modifications would contribute to the dysregulation of miRNAs in acute lymphoblastic leukaemia (ALL), the effect of a histone deacetylase inhibitor, trichostatin A (TSA), on miRNA expression profile was analysed by microarray assay in a precursor B-cell ALL cell line NALM-6. A total of 10 miRNAs were downregulated and 31 were upregulated significantly following TSA treatment. Among TSA-upregulated miRNAs, MIR22 is an extronic miRNA and resides in the second exon of the non-coding transcript MGC14376. Upregulation of MIR22 transcription was found in both NALM-6 cells and primary human ALL malignant cells treated with TSA. Whereas a CpG island was identified within the promoter element of MIR22, no promoter DNA methylation was detected in these cells. In contrast, accumulation of the repressive histone marker H3K27 trimethylation (H3K27triM) was identified around the transcriptional start point of the gene, which was reduced by TSA treatment. Thus, accumulation of H3K27triM independent of promoter DNA methylation may be a novel epigenetic mechanism for MIR22 silencing in ALL.
British Journal of Haematology 10/2009; 148(1):69-79. · 4.94 Impact Factor
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Analytical Letters 10/2009; 42(15):2460-2473. · 1.02 Impact Factor
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ABSTRACT: The electrochemical deposition of Co nanoparticles on carbon ionic liquid electrode (CILE) was described and further used as the platform to construct a myoglobin (Mb) electrochemical biosensor. CILE was prepared by mixing a certain ratio of carbon powder, 1-ethyl-3-methylimidazolium tetrafluoroborate (EMIMBF4), and liquid paraffin together. The presence of ionic liquid on the electrode surface facilitated the formation of Co nanoparticles, and a layer of Co nanoparticles was deposited on the surface of CILE with the average diameter of 300 nm after the cyclic voltammetic scan in the CoCl2 solution. The formed Co/CILE was used as a new basal electrode for the investigation on the direct electrochemistry of protein. Mb molecules were further cast on the surface of Co/CILE and immobilized with Nafion film. The fabricated Nafion/Mb/Co/CILE showed good electrochemical behaviors with a pair of well-defined quasi-reversible redox peaks of Mb obtained, which was attributed to the electrochemical reaction of heme Fe(III)/Fe(II) redox couples. The results indicated that the presence of Co nanoparticles exhibited great promotion to the direct electron transfer of Mb. The Mb electrochemical biosensor showed good electrocatalytic activity to the reduction of hydrogen peroxide and trichloroacetic acid (TCA). The modified electrodes showed good stability and reproducibility, which had potential application in third generation biosensor.
06/2009;
