Lijian Yang

Jinan University (Guangzhou, China), Shengcheng, Guangdong, China

Are you Lijian Yang?

Claim your profile

Publications (67)125.02 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Acute promyelocytic leukemia (APL) is characterized by the reciprocal translocation t(15;17), which fuses PML with retinoic acid receptor alpha (RARalpha). Although PML-RARalpha is crucially important for pathogenesis and responsiveness to treatment, the molecular and cellular mechanisms by which PML-RARalpha exerts its oncogenic potential have not been fully elucidated. Recent reports have suggested that long non-coding RNAs (lncRNAs) contribute to the precise control of gene expression and are involved in human diseases. Little is known about the role of lncRNA in APL.
    BMC Cancer 09/2014; 14(1):693. · 3.33 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Previous studies have shown that occupational lead (Pb) exposure might influence human T-lymphocyte function, including such as changes in T-cell receptor (TCR) Vβ and Vγ repertoire and in expression of the TCRζ gene. Thus, the study here further investigated expression of TCRζ-related factors and the FcεRIγ gene (whose product has a functional role complementary to the TCRζ chain) and the Elf-1 gene whose product is involved in regulation of TCR expression. Quantitative real-time RT-PCR was used to measure expression of TCRζ, FcεRIγ, and Elf-1 genes in peripheral blood mononuclear cells (PBMC) isolated from 17 Pb-exposed workers. Samples were collected before and after the workers had undergone chelation therapy regimens. Twenty-three healthy individuals served as controls. The results showed that TCRζ, FcεRIγ, and Elf-1 gene expression in Pb-exposed workers before chelation therapy was significantly lower than in PBMC from healthy individuals. After chelation therapy, expression of TCRζ appeared to trend toward normal levels; in comparison, lower expressions of FcεRIγ and Elf-1 persisted. In conclusion, the previously-documented impairment of T-lymphocyte functions and T- lymphocyte-mediated immune responses seen previously in response to occupational Pb exposure might be attributable, in part, to effects on TCR signaling pathways - including those related to TCRζ and FcεRIγ - and to any down-regulation of membrane TCRζ expression/activity that might be associated with Pb-induced effects on Elf-1 expression.
    Journal of Immunotoxicology 04/2014; · 1.57 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A20 is a repressor of NF-κB and was recently shown to be frequently inactivated by deletions or mutations in several types of lymphomas including T-cell lymphoma. Little is known about the characteristics of A20 mutations in T-cell acute lymphoblastic leukemia (T-ALL). In this study, we analyzed A20 polymorphisms and characterized their features in 11 cases with T-ALL, 30 samples from healthy Chinese individuals, and 3 cells lines including CCRF-CEM, Molt-4, and Toledo cells. Two frequent A20 polymorphisms were found: a CCT deletion at position 12384 and a nucleotide exchange (A to C) at position 13751 (rs2307859 and rs661561). The homozygous form (CC) of rs661561 was detected in all 10 cases with detectable T-ALL, while only 80% (24/30) of the healthy controls had this genotype. We found one T-ALL case without the above frequent single-nucleotide polymorphisms (SNPs) in which a T to G mutation at position 12486 was found, which results in an amino acid exchange (Phe127Cys; rs2230926). Similar results were found in Molt-4 cells, which lack the frequent SNPs but have a heterozygous polymorphism at position 13749 (C > T) (rs5029948). Interestingly, the T-ALL case with the Phe127Cys mutation and Molt-4 cells demonstrated a high A20 copy number as measured by real-time polymerase chain reaction amplification with three primer sets that cover different regions of the A20 gene, corresponding to a high A20 and low NF-κB expression level. In conclusion, we characterized the features of A20 polymorphisms in T-ALL, and found that a low frequency A20 mutation, which was thought to be involved in malignant T-ALL development, might function differently in T cell lymphomas.
    Hematology (Amsterdam, Netherlands) 03/2014; · 1.33 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Graft versus host disease (GVHD) is the main complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Recent data indicated that regulatory T (Treg) cells might relate to GVHD, and such functions might be mediated by certain T-cell receptor (TCR) subfamily of Treg cells. Thus, we analyzed the distribution and clonality of the TCR Vα and Vβ repertoire of Treg cells from leukemia patients with and without GVHD after allo-HSCT. Numerous TCR Vα subfamilies, including Vα1, Vα9, Vα13, Vα16-19, and Vα24-29, were absent in Treg cells after allo-HSCT. The usage numbers for the TCR Vα and Vβ subfamilies in Treg cells from patients without GVHD appeared more widely. The expression frequencies of Vα10 or Vα20 between both groups were significantly different. Moreover, the expression frequency of TCR Vβ2 subfamily in patients without GVHD was significantly higher than that in patients with GVHD. Oligoclonally expanded TCR Vα and Vβ Treg cells were identified in a few samples in both groups. Restricted utilization of the Vα and Vβ subfamilies and the absence of some important TCR rearrangements in Treg cells may be related to GVHD due to a lower regulating function of Treg subfamilies.
    DNA and cell biology 01/2014; · 2.28 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Knowledge of the oncogenic signaling pathways of T-cell acute lymphoblastic leukemia (T-ALL) remains limited. Constitutive aberrant activation of the nuclear factor kappa B (NF-κB) signaling pathway has been detected in various lymphoid malignancies and plays a key role in the development of these carcinomas. The zinc finger-containing protein, A20, is a central regulator of multiple NF-κB-activating signaling cascades. A20 is frequently inactivated by deletions and/or mutations in several B-and T-cell lymphoma subtypes. However, few A20 mutations and polymorphisms have been reported in T-ALL. Thus, it is of interest to analyze the expression characteristics of A20 and its regulating factors, including upstream regulators and the CBM complex, which includes CARMA1, BCL10, and MALT1.
    European journal of medical research 01/2014; 19(1):62. · 1.10 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Rheumatoid arthritis (RA) is an inflammatory autoimmune disorder; abnormal T cell immunity plays a critical role in the development of RA. Recently, A20 was identified as a key negative regulator for T cell activation and inflammatory signaling and may be involved in RA pathogenesis. In this study, we analyzed the expression level of A20, NF-κB, and A20 regulatory factor mucosa-associated lymphoid tissue lymphoma translocation gene 1 (MALT1) in patients with RA. Real-time PCR was used to determine the expression level of MALT1, MALT-V1, A20, and NF-κB genes in RA and healthy individuals (HI). Significantly lower A20 expression was found in RA patients compared with those in the healthy group, while NF-κB overexpression could be detected in patients with RA. Moreover, the MALT1 and MALT1-V1 expression level was downregulated in RA patients. A positive correlation between MALT1 and A20 and MALT1-V1 and A20 was found in patients with RA, and a tendency towards a negative correlation was found between MALT1 and NF-κB, MALT1-V1 and NF-κB, and A20 and NF-κB. In conclusion, we first characterized the alternative expression pattern of MALT1, A20, and NF-κB in RA, which may be related to abnormal T cell activation.
    Research Journal of Immunology 01/2014; 2014:492872.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The miR-29 family have been demonstrated acting as vital tumor suppressor in multiple cancers as well as regulators in the adaptive immune system. Little is known about their role in leukemogenesis. The purpose of this study is to analyze the expression pattern of miR-29a/29b and its target genes Mcl-1 (myeloid cell leukemia sequence 1) and B-cell lymphoma 2 (Bcl-2) in myeloid leukemia.
    Experimental hematology & oncology. 01/2014; 3:17.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Cell-mediated immunity is often suppressed in patients with hematological malignancies. Recently, we found that low T cell receptor (TCR)-CD3 signaling was related to abnormal expression of the negative regulator of nuclear factor kappa B (NF-κB) A20 in acute myeloid leukemia. To investigate the characteristics of T cell immunodeficiency in lymphomas, we analyzed the expression features of A20 and its upstream regulating factor mucosa-associated lymphoid tissue lymphoma translocation gene 1 (MALT1) and genes downstream of NF-κB in patients with different lymphoma subtypes, including T cell non-Hodgkin lymphoma (T-NHL), B cell non-Hodgkin lymphoma (B-NHL) and NK/T cell lymphoma (NK/T-CL). Real-time PCR was used to determine the expression level of the MALT1, MALT-V1 (variant 1), A20 and NF-κB genes in peripheral blood mononuclear cells (PBMCs) from 24 cases with T-NHL, 19 cases with B-NHL and 16 cases with NK/T-CL, and 31 healthy individuals (HI) served as control. Significantly lower A20 and NF-κB expression was found in patients with all three lymphoma subtypes compared with the healthy controls. Moreover, the MALT1 expression level was downregulated in all three lymphoma subtypes. A significant positive correlation between the expression level of MALT1 and A20, MALT1-V1 and A20, MALT1-V1 and NF-κB, and A20 and NF-κB was found. An abnormal MALT1-A20-NF-κB expression pattern was found in patients with lymphoma, which may result a lack of A20 and dysfunctional MALT1 and may be related to lower T cell activation, which is a common feature in Chinese patients with lymphoma. This finding may at least partially explain the molecular mechanism of T cell immunodeficiency in lymphomas.
    Cancer Cell International 01/2014; 14:36. · 2.09 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Despite significant improvement in our understanding of T-cell acute lymphoblastic leukemia (T-ALL) biology and pathogenesis, many questions remain unanswered. In previous studies, we found a T-ALL case with two malignant T-cell clones with Vδ1Dδ2Dδ3Jδ1 and Vδ2Dδ3Jδ2 rearrangements. In this study, we further characterized T-ALL cases with two malignant clones containing Vδ1Dδ3Jδ1 and Vδ2Dδ1Jδ1 rearrangements using fine-tiling array comparative genomic hybridization, ligation-mediated polymerase chain reaction (LM-PCR), sequencing, and reverse transcription polymerase chain reaction (RT-PCR) analysis. We further analyzed the distribution and clonality of the T-cell receptor (TCR) Vγ and Vδ subfamily T cells in the two T-ALL cases by RT-PCR and GeneScan. Monoclonal Vδ1 and Vδ2 subfamilies were confirmed in both samples, the Vδ3 through Vδ7 subfamilies could not be detected in the T-ALL samples, whereas the oligoclonal Vδ8 subfamily could be identified. Based on the clinical finding that both of the T-ALL cases with two malignant T-cell clones had a poor outcome, we attempted to compare the expression pattern of genes related to T-cell activation and proliferation between cases with the malignant Vδ1 and Vδ2 T-cell clones and T-ALL cases with a mono-malignant Vα T-cell clone. We selected two T-ALL cases with VαJα rearrangements and analyzed the expression level of Notch1, TAL1, and the CARMA-BCL10-MALT-A20-NF-κB pathway genes by real-time PCR. A20 had significantly higher expression in the biclonal compared with the monoclonal T-ALL group (p=0.0354), and there was a trend toward higher expression for the other genes in the biclonal group with the exception of TAL1, although the differences were not statistically significant. In conclusion, we identified two T-ALL cases with biclonal malignant T-cell clones and described the characteristics of the biclonal T-ALL subtype and its gene expression pattern. Thus, our findings may improve the understanding of biclonal T-ALL.
    DNA and cell biology 12/2013; · 2.28 Impact Factor
  • Source
    Li Shi, Shaohua Chen, Lijian Yang, Yangqiu Li
    [Show abstract] [Hide abstract]
    ABSTRACT: T-cell activation and dysfunction relies on direct and modulated receptors. Based on their functional outcome, co-signaling molecules can be divided as co-stimulators and co-inhibitors, which positively and negatively control the priming, growth, differentiation and functional maturation of a T-cell response. We are beginning to understand the power of co-inhibitors in the context of lymphocyte homeostasis and the pathogenesis of leukemia, which involves several newly described co-inhibitory pathways, including the programmed death-1 (PD-1) and PD-1 ligand (PD-L1) pathway. The aim of this review is to summarize the PD-1 and PD-L1 biological functions and their alterative expression in hematological malignancies. The role of PD-1 and PD-L1 in T-cell immune suppression and the potential for immunotherapy via blocking PD-1 and PD-L1 in hematological malignancies are also reviewed.
    Journal of Hematology & Oncology 09/2013; 6(1):74. · 4.46 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Despite the success of imatinib and other tyrosine kinase inhibitors (TKIs), chronic myeloid leukemia (CML) remains largely incurable, and a number of CML patients die due to Abl mutation-related drug resistance and blast crisis. The aim of this study was to evaluate proliferation inhibition and apoptosis induction by down-regulating PPP2R5C gene expression in the imatinib-sensitive and imatinib-resistant CML cell lines K562, K562R (imatinib resistant without an Abl gene mutation), 32D-Bcr-Abl WT (imatinib-sensitive murine CML cell line with a wild type abl gene) and 32D-Bcr-Abl T315I (imatinib resistant with a T315I Abl gene mutation) and primary cells from CML patients by RNA interference. PPP2R5C siRNAs numbered 799 and 991 were obtained by chemosynthesis. Non-silencing siRNA scrambled control (SC)-treated, mock-transfected, and untreated cells were used as controls. The PPP2R5C mRNA and protein expression levels in treated CML cells were analyzed by quantitative real-time PCR and Western blotting, and in vitro cell proliferation was assayed with the cell counting kit-8 method. The morphology and percentage of apoptosis were revealed by Hoechst 33258 staining and flow cytometry (FCM). The results demonstrated that both siRNAs had the best silencing results after nucleofection in all four cell lines and primary cells. A reduction in PPP2R5C mRNA and protein levels was observed in the treated cells. The proliferation rate of the PPP2R5C-siRNA-treated CML cell lines was significantly decreased at 72 h, and apoptosis was significantly increased. Significantly higher proliferation inhibition and apoptosis induction were found in K562R cells treated with PPP2R5C-siRNA799 than K562 cells. In conclusion, the suppression of PPP2R5C by RNA interference could inhibit proliferation and effectively induce apoptosis in CML cells that were either imatinib sensitive or resistant. Down-regulating PPP2R5C gene expression might be considered as a new therapeutic target strategy for CML, particularly for imatinib-resistant CML.
    Journal of Hematology & Oncology 09/2013; 6(1):64. · 4.46 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Recently, alterations in the expression pattern of PPP2R5C associated with malignant transformation have been characterized, and PPP2R5C overexpression was demonstrated in leukemias. To confirm the role of PPP2R5C in proliferation and its molecular mechanism, three PPP2R5C-siRNAs and a scrambled nonsilencing siRNA control were used to treat Molt-4 and Jurkat T cells. After nucleofection, PPP2R5C expression and biological consequences based on a highly efficient and specific PPP2R5C-siRNA were demonstrated by qRT-PCR, CCK-8 assay, Annexin V/PI, and flow cytometry. The global gene expression profile of PPP2R5C-siRNA-treated Jurkat T cells was established. A significant reduction in the PPP2R5C mRNA level was observed at 24 to 72 h in Molt-4 and Jurkat T cells with all of the PPP2R5C-siRNAs. The proliferation rate of Molt-4 and Jurkat T cells transfected with different PPP2R5C-siRNAs was significantly decreased at 72 h compared with the control (p<0.05). However, the transfected cells did not show a significant increase in Annexin V/PI-positive cells (apoptosis). The highly efficient PPP2R5C-siRNA2 was used to treat Jurkat T cells for gene expression profile analysis. In total, 439 genes were upregulated, and 524 genes were downregulated at least twofold in PPP2R5C-siRNA-treated Jurkat T cells. Changes in signaling pathway genes closely related to the TCR, Wnt, calcium, MAPK, and p53 signaling pathways were observed. In conclusion, the suppression of PPP2R5C by RNA interference could effectively inhibit the proliferation of leukemic T cells, the PPP2R5C-siRNA treatment altered gene expression profiles, and the differential expression of the glycogen synthase kinase 3 beta (GSK-3β), ataxia telangiectasia mutated (ATM), and Mdm2 p53 binding protein homolog (MDM2) genes may play an important role in the effects of PPP2R5C knockdown in Jurkat T cells.
    DNA and cell biology 08/2013; · 2.28 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective To investigate c-Cbl and Cbl-b gene expressions in peripheral blood mononuclear cells (PBMCs) from multiple myeloma (MM) patients. Methods SYBR(R); Green PCR technique was used to detect c-Cbl and Cbl-b gene expressions in PBMCs from 23 MM patients and 22 healthy individuals, and RT-PCR and DNA sequence analysis were performed to analyze the mutations of 7-10 exons of c-Cbl. Results The expression of c-Cbl gene in MM patients (median: 0.798%) significantly decreased as compared with that in healthy controls (median: 2.443%) (P<0.05). The expression of Cbl-b gene in MM patients (median: 0.714%) also dropped significantly as compared with that in healthy controls (median: 2.179%) (P<0.05). The 7-10 exons of c-Cbl gene had two different sizes of fragments in 2 MM patients: 483 bp and 148 bp which were wild-type and deletion mutants type of c-Cbl gene. c-Cbl gene mutations were not found in all MM patients. Conclusion The expressions of c-Cbl and Cbl-b genes in PBMCs from MM patients are down-regulated.
    Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology 08/2013; 29(8):842-5.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To improve the outcome of patients with T-cell acute lymphoblastic leukemia (T-ALL), characterization of the biological features of T-ALL blast cells and the immune status of patients with T-ALL is needed to identify specific therapeutic strategies. Using a novel approach based on the combination of fine-tiling comparative genomic hybridization (FT-CGH) and ligation-mediated PCR (LM-PCR), we molecularly identified a malignant gammadelta + T cell clone with a Vdelta5Ddelta2Jdelta1 rearrangement that was paired with a T cell receptor (TCR) VgammaI and comprised a Vgamma1Vdelta5 T cell clone in a relapse T-ALL patient. This malignant Vdelta5 T cell clone disappeared after chemotherapy, but the clone was detected again when disease relapsed post allogeneic hematopoietic stem cell transplantation (allo-HSCT) at 100 weeks. Using PCR and GeneScan analyses, the distribution and clonality of the TCR Vgamma and Vdelta subfamilies were examined before and after allo-HSCT in the patient. A reactive T cell clone with a Vdelta4Ddelta3Jdelta1 rearrangement was identified in all samples taken at different time points (i.e., 4, 8, 68, 100 and 108 weeks after allo-HSCT). The expression of this Vdelta4+ T cell clone was higher in the patient during complete remission (CR) post allo-HSCT and at disease relapse. This study established a sensitive methodology to detect T cell subclones, which may be used to monitor minimal residual disease and immune reconstitution.
    Molecular Cancer 07/2013; 12(1):73. · 5.13 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To elucidate the characteristics of T-cell receptor (TCR) signal transduction in T-cells from acute myeloid leukemia (AML), the mucosa-associated-lymphoid-tissue lymphoma-translocation gene 1 (MALT1), A20, NF-kappaB and MALT1-V1 gene expression levels in CD3+ T cells sorted from the peripheral blood of patients with AML were analyzed by real-time PCR. A significantly lower MALT1 and A20 expression level was found in T cells from patients with AML compared with healthy controls (p = 0.045, p < 0.0001); however, the expression level of MALT1-V1 (variant 1) was significantly higher in the AML group than in the healthy control group (p = 0.006), and the expression level of NF-kappaB was increased in the AML group. In conclusion, the characteristics of the expression pattern of MALT1-A20-NF-kappaB and the distribution of MALT1 variants in T cells from AML were first characterized. Overall, low TCR-CD3 signaling is related to low MALT1 expression, which may related to T cell immunodeficiency, while the up-regulation of MALT1-V1 may play a role in overcoming the T cell activity by downregulating A20 in patients with AML, which may be related to a specific response to AML-associated antigens.
    Cancer Cell International 04/2013; 13(1):37. · 2.09 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: INTRODUCTION: SALL4 and BMI-1 are important factors in hematopoiesis. Placental tissue (PT) and umbilical cord blood (CB) are rich in hematopoietic stem/progenitor cells (HSCs/HPCs), but their SALL4 and BMI-1 expression levels remain unknown. METHOD: Real-time PCR was used to determine the expression level of these genes in PT and CB from ten cases, and ten healthy donors were used as control. RESULTS: A significantly higher BMI-1 and SALL4 gene expression level was found in PT (median: 17.548 and 34.362, respectively) than in cord blood mononuclear cells (CBMCs) (median: 2.071 and 11.300, respectively) (P = 0.0001 and P = 0.007) and healthy peripheral blood mononuclear cells (PBMCs) (median: 0.259 and 0.384, respectively) (P = 0.001 and P < 0.0001), and their expression level was lower in PBMCs than in CBMCs (P = 0.029 and P = 0.002). A positive correlation between the BMI-1 and SALL4 genes was found in the PT and CB groups, while there was no significant correlation between these genes in the healthy group. There was also no significant correlation between the expression level of each gene in PT and CB. CONCLUSIONS: These results describe the characteristic features of the BMI-1 and SALL4 gene expression pattern in placental tissue and cord blood. Placental tissue with higher expression level of both genes may be considered as a potential resource for SALL4-related HPC expansion.
    Stem Cell Research & Therapy 04/2013; 4(2):49. · 3.65 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: A previous study has demonstrated a significant decrease in the TCRzeta gene expression level in chronic myeloid leukemia (CML); thus, we further investigated the expression of TCRzeta-regulating factors, the distribution of the TCRzeta 3' untranslated region (3'-UTR) splice variants, and the expression level and correlation of the alternative splicing factor/splicing factor 2 (ASF/SF-2), FcepsilonRIgamma and ZAP-70 genes. TCRzeta 3'-UTR splice variants were identified in peripheral blood mononuclear cells (PBMCs) from 14 healthy individuals, 40 patients with CML and 22 patients with CML in complete remission (CML-CR) by RT-PCR. The expression level of the TCRzeta, FcepsilonRIgamma, ASF/SF-2 and ZAP-70 genes was analyzed by real-time quantitative PCR. While the expression of TCRzeta gene in the CML group was significantly lower than that in the healthy individual and CML-CR groups, a significantly higher expression of the FceRIgamma and ASF/SF-2 genes was found in the CML group. Two types of splicing forms were detected in all of the healthy individual CML-CR cases: wild type (WT) TCRzeta 3'-UTR and alternatively splieced (AS) TCRzeta 3'-UTR which have been alternatively splieced in the WT TCRzeta 3'-UTR . However, 35% of the CML cases contained only the wild type TCRzeta 3'-UTR isoform. Based on the TCRzeta 3'-UTR isoform expression characteristic, we divided the patients with CML into two subgroups: the WT+AS- CML group, containing patients that express only the wild type TCRzeta 3'-UTR, and the WT+AS+ CML group, which contained patients that expressed two TCRzeta 3'-UTR isoforms. A significantly different ASF/SF-2 and FcepsilonRIgamma gene expression pattern was found between the WT+AS- and WT+AS+CML groups. We concluded that defective TCRzeta expression may be characterized in the WT+AS-and WT+AS+CML subgroups by the different gene expression pattern. The overexpression of ASF/SF2, which alternatively splices the TCRzeta [unknown]3'-UTR, is thought to participate in feedback regulation. The characteristics of TCRzeta 3'-UTR alternative splicing may be a novel immunological marker for the evaluation of the CML immune status.
    Journal of Hematology & Oncology 12/2012; 5(1):74. · 4.46 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The B-cell chronic lymphocytic leukemia (CLL)/lymphoma 11B (BCL11B) gene plays a critical role in T-cell differentiation and proliferation. However, little is understood about the role of BCL11B in human hematopoietic stem/progenitor cells. Small interfering RNA (siRNA)-mediated suppression of the BCL11B was shown to induce apoptosis in human T-cell acute lymphoblastic leukemia cells. To further characterize the role of BCL11B in hematopoietic stem/progenitor cells and assess the safety of siRNA-mediated targeted therapy, the in vitro differentiation and proliferation of CD34(+) cells after BCL11B-siRNA935 treatment were studied. CD34(+) cells were sorted from three cases of umbilical cord blood by the magnetic activated cell sorting technique, and the purity was identified by flow cytometry. BCL11B-siRNA935 was delivered into CD34(+) cells by nucleofection and the BCL11B expression level was analyzed by quantitative real-time polymerase chain reaction. Erythroid burst-forming units (BFU-E), granulocyte/macrophage colony-forming units (CFU-GM), and megakaryocyte colony-forming units (CFU-Meg) were assessed using BCL11B-siRNA935-treated CD34(+) cells by the methylcellulose semi-solid culture method. The BCL11B expression level in CD34(+) cells was significantly lower than that in Molt-4 cells and peripheral blood mononuclear cells from healthy individuals. An approximate one-fold reduction in the BCL11B mRNA level was observed 24 hours post-transfection with BCL11B-siRNA935. However, there was no significant difference on the colony formation ability of BFU-E, CFU-GM, and CFU-Meg for CD34(+) cells between the BCL11B-siRNA935-treated and mock-transfected groups (P > 0.05). BCL11B suppression by RNA interference had no significant influence on the differentiation and proliferation of CD34(+) cells. In conclusion, the BCL11B-siRNA935 used in this study may be safe, and BCL11B may be considered a new candidate for targeted gene therapy in T-cell malignancies.
    Hematology (Amsterdam, Netherlands) 11/2012; 17(6):329-33. · 1.33 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background and methodsIn order to characterize the expression pattern of SALL4, BMI-1 and ABCA3 genes in patients with myeloid leukemia and those who achieved complete remission (CR) after chemotherapy. Real-time PCR was used to determine the expression level of these genes in peripheral blood mononuclear cells from 24 patients with AML, eight patients with AML-CR, 13 patients with CML in the chronic phase (CML-CP), 12 patients with CML in blast crisis (CML-BC), 13 patients with CML-CR and 11 healthy individuals (HI). RESULTS: Overexpression of the BMI-1 gene was found in the AML, CML-CP and CML-BC groups as compared with HI group, while the BMI-1 expression level was lower in patients who achieved CR. In contrast, significantly increased SALL4 expression was only found in AML group, additionally, SALL4 expression was lower in the CML-CP and CML-CR groups compared with the HI group, while the SALL4 expression level in the CML-BC group was higher and significantly greater than that in the CML-CP and CML-CR groups. Moreover, a positive correlation between the expression of SALL4 and BMI-1 genes was found in samples from most groups. There was no significant difference of ABCA3 expression level in AML and CML-BC group in comparison with HI group. Interestingly, the ABCA3 expression level was significantly decreased in the CML-CP, AML-CR and CML-CR in comparison with the HI group. Moreover, the ABCA3 expression level in all of the CR groups was lower than that in their corresponding groups. CONCLUSIONS: These results describe the altered SALL4, ABCA3 and BMI-1 expression pattern in different phases of myeloid leukemia, which may relate to the development and progression to different diseases. SALL4 expression was strongly correlated with BMI-1 in most of the myeloid leukemia patient groups, providing a potential link between SALL4 and BMI-1 in leukemogenesis.
    Cancer Cell International 10/2012; 12(1):42. · 2.09 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: T-cell immunodeficiency is a common feature in patients with chronic myeloid leukemia (CML), and deficiency in CD3 levels was detected in T cells from these patients, which may represent a characteristic that is related to a lower T cell activation. In this study, we explored the possibility that forced TCRζ gene expression may upreg-u-late T cell receptor (TCR) signaling activation and reverse interleukin-2 (IL-2) production in T cells from patients with CML. A recombinant eukaryotic vector expressing TCRζ was transfected into T cells by nucleofection. Phosphorylated TCRζ, phosphorylated NF-κB, and the IL-2 level in TCRζ-transfected CD3+T cells that were activated with anti-CD3 and anti-CD28 antibodies were measured by Western blot and enzyme-linked immunosorbent assay (ELISA). Significantly increased TCRζ levels were found in TCRζ-transfected CD3+T cells. After CD3 and CD28 antibody stimulation, a significantly higher phosphorylated TCRζ chain level was demonstrated, and an increased IL-2 production in TCRζ-upregulated T cells was associated with the increased expression of the phosphorylated NF-κB. In conclusion, TCRζ gene transfection could restore TCRζ chain deficiency and enhance IL-2 production in T cells from patients with CML. It is possible that TCRζ chain reconstitution in leukemia-specific, clonally expanded T cells will effectively increase their activation of antileukemia cytotoxicity.
    DNA and cell biology 10/2012; 31(11):1628-35. · 2.28 Impact Factor

Publication Stats

219 Citations
125.02 Total Impact Points

Institutions

  • 2002–2014
    • Jinan University (Guangzhou, China)
      • Department of Biochemistry
      Shengcheng, Guangdong, China
  • 2012
    • Monash University (Australia)
      • Faculty of Medicine, Nursing and Health Sciences
      Melbourne, Victoria, Australia
    • Guangdong Academy of Medical Sciences and General Hospital
      Shengcheng, Guangdong, China
  • 2011
    • Guangzhou University
      Shengcheng, Guangdong, China
  • 2010
    • University of Jinan (Jinan, China)
      Chi-nan-shih, Shandong Sheng, China
    • Guangzhou Medical University
      Shengcheng, Guangdong, China