Dan-Dan Zhao

Tianjin Medical University Cancer Institute and Hospital, T’ien-ching-shih, Tianjin Shi, China

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Publications (13)0 Total impact

  • Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi 10/2013; 34(10):900-3.
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    ABSTRACT: Lymphoblastic lymphoma (LBL) comprises 2% to 4% of non-Hodgkin lymphomas cases in adults, of which 85% to 90% of LBL in adults is of T-cell phenotype. This study was aimed to evaluate the clinical characteristics and prognostic factors of patients with mediastinal T-LBL. Based on the retrospective analysis of the clinical data of 35 patients with mediastinal T-LBL during the period from January 1998 to January 2011, the clinical characteristics and prognostic factors of mediastinal T-LBL were summarized. The results showed that the total of 35 patients were identified (male 24 and female 11), with a median age of 19 (5 - 52) years. The majority of patients were in stage III/IV, 16 cases (45.7%) presented bulky mediastinal mass. Intrathoracic effusions (pleural, pericardial) were not uncommon (62.9%). Overall survival rate (OS) and progression-free survival rate (PFS) at 3 years for the entire cohort were 36% and 24%, respectively. OS and PFS at 5 years were 25% and 16.7%, respectively. Anemia at diagnosis were an important, independent predictor of OS (P = 0.048). Bulky mass (P = 0.048), superior vena cava syndrome (P = 0.021), and abnormal PLT count at diagnosis was the independent prognostic factors for PFS (P = 0.021). It is concluded that the patients with primary mediastinal T-LBL are characterized by a low incidence, bad prognosis, and short survival. For patients accompanying with anemia, bulky mass and superior vena cava syndrome, their prognosis is worse.
    Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology 03/2013; 21(2):377-82.
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    ABSTRACT: Alteration in the balance between cell apoptosis and proliferation is one of the pathophysiological mechanisms of the myelodysplastic syndromes (MDS). The question of whether the excessive apoptosis and/or proliferation predominantly involve the subset of progenitor cells (CD34(+) cells) or mature cells (CD34(-) cells) remains a controversial issue. This study was purposed to analyze the apoptosis and proliferation status of CD34(+) and CD34(-) cells in bone marrow (BM) of patients with MDS, to investigate the pathogenesis of MDS and to determine the relation of apoptosis and proliferation status of CD34(+) and CD34(-) cells with prognosis of MDS. The proprotion of CD34(+) cells, the apoptosis and proliferation ratio (A/P) of CD34(+) and CD34(-) cells in BM of 40 patients with MDS, including 20 cases of high-risk MDS and 20 cases of low-risk MDS, and 10 normal persons as control were detected by flow cytometry; the influence of CD34(+) and CD34(-) cell apoptosis and proliferation levels on prognosis of MDS was evaluated by unvariate and multivariate analysis of survival. The results showed that the proportion of CD34(+) cells in BM of high-risk MDS patients was significantly higher than that in BM of low-risk MDS patients and in normal BM [(1.92 ± 0.10)%, (1.09 ± 0.04)%, (1.03 ± 0.05)% respectively]. The apoptotic rates (AR) of both CD34(+) and CD34(-) cells were significantly higher in low-risk MDS [(54.75 ± 2.18)%, (80.36 ± 1.68)%] than in high-risk MDS [(24.87 ± 2.69)%, (23.12 ± 1.23)%] and in normal BM [(18.51 ± 2.74)%, (20.98 ± 2.21)%]. When compared between CD34(+) cells and CD34(-) cells in low-risk MDS, a greater AR of CD34(-) cells was found. However, the higher proliferative rate of CD34(+) cells was observed in high-risk MDS. In low-risk MDS, a higher A/P ratio was found in CD34(-) cells than in CD34(+) cells; whereas this ratio was equalized or inverted in high-risk MDS. In addition, the survival and prognosis correlated significantly with AR of CD34(+) cells. It is concluded that the early MDS is predominantly associated with excessive apoptosis of the mature CD34(-) cells. The proliferation rate of cells increases with the disease progression in MDS subsets, especially, in the subset of CD34(+) cells. Surprisingly, the apoptosis of CD34(+) cells may be a useful prognostic factor, and the inhibition of apoptotic mechanisms may induce the transformation of MDS to leukemia.
    Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology 11/2012; 20(6):1392-7.
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    ABSTRACT: To explore the role of SHP-1 promoter methylation on the pathogenesis and progression in myelodysplastic syndromes (MDS) and its related mechanism. 63 MDS patients were divided into low-grade (LG) group and high-grade (HG) group according to IPSS score system. Bone marrow samples were collected. Methylation specific-PCR (MSP) were used to detect the status of SHP-1 promoter methylation in bone marrow (BM) samples from different risk MDS patients and MDS cell line, SKK-1. Western blot was used to detect signal transduction and activator of transcription (STAT3) activation in SKK-1 cell line and MDS patients. No SHP-1 promoter methylation could be detected in healthy controls BM. Partially methylation was found in SKK-1 cell line. Methylation rate of SHP-1 gene promoter was found in BM of 24.2% of low-grade MDS patients and 63.3% of high-grade MDS patients, the difference between these two groups was statistically significant (P < 0.05); Patients were divided into different groups according to WHO subtype, chromosomal karyotype and blast cells in bone marrow, methylation rates of SHP-1 were significantly higher in RAEB-II, poor karotype group and samples with 0.11-0.19 blast cells (P < 0.05); The phosphorylation protein of STAT3 was detected in SKK-1 cell line. The expression of phosphorylation STAT3 was significantly higher in HG group than in LG group (66.7% vs 18.2%) (P < 0.05). There was a significant correlation between SHP-1 promoter methylation and STAT3 phosphorylation. Abnormal methylation of SHP-1 gene promoter might have tentative role in the pathogenesis and progression of MDS, which may be involved in STAT3 activation. Detection of SHP-1 promoter methylation may be helpful to evaluate the prognosis of MDS.
    Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi 02/2012; 33(2):108-12.
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    ABSTRACT: To explore the expression of stromal cell derived factor-1 (SDF-1) and its receptor CXCR4 in myelodysplastic syndromes (MDS). A total of 59 patients with a diagnosis of MDS were divided into low-grade (n = 33) and high-grade (n = 26) groups according to international prognostic scoring system (IPSS). Bone marrow (BM) samples were collected. The SDF-1 and VEGF levels in BM plasma, CXCR4 expression on BM CD34(+) cell and the apoptosis of CD34(+) cells were measured. The SDF-1 levels in MDS patients were significantly higher than those of normal controls [(689 ± 190) ng/L, P < 0.05]. And the low-grade group was significantly higher than that of high-grade group [(2301 ± 413) vs (1173 ± 501) ng/L]. CXCR4 expression on CD34(+) cells were significantly higher in high-grade group (68.1% ± 18.8%) than that of both low-grade (21.0% ± 9.7%) and control groups (19.4% ± 5.3%) (P < 0.05). Apoptotic rate of CD34(+) cells were 54.8% ± 10.2% in low-grade group, 24.3% ± 7.9% in high-grade group and 18.5% ± 8.7% in control group. It significantly increased in low-grade group versus other groups (P < 0.05). VEGF levels were significantly higher in MDS patients in low-grade group [(286 ± 97) ng/L] and high-grade group [(407 ± 168) ng/L] versus control group [(157 ± 46) ng/L, P < 0.05]. A positive correlation was found between apoptosis of CD34(+) cells and SDF-1 levels in low-grade group (r = 0.805, P < 0.05), VEGF levels and CXCR4 expression rate in high-grade group (r = 0.683, P < 0.05). The expression of SDF-1/CXCR4 is significantly abnormal in MDS patients. And it is correlated with apoptosis and angiogenesis. Intervention of SDF-1/CXCR4 axis may provide a new therapeutic target.
    Zhonghua yi xue za zhi 12/2011; 91(46):3275-7.
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    ABSTRACT: The study was aimed to investigate the expression of stromal cell derived factor (SDF-1) in bone marrow (BM) and its relation with apoptosis of BM CD34(+) cell and angiogenesis in myelodysplastic syndrome (MDS). 40 patients with MDS were divided into low-risk group and high-risk group according to IPSS score system. BM samples were collected. SDF-1 levels, the apoptosis of CD34(+) cells and microvessel density (MVD) of BM were detected by ELISA, flow cytometry and immunochemistry, respectively. The results showed that the SDF-1 level in MDS patients was significantly higher than that in normal controls(p < 0.05), and SDF-1 level in low-risk group was significantly higher than that in high-risk group. Apoptosis of CD34(+) cells significantly increased in low-risk group compared with other groups (p < 0.05). MVD in BM biopsy significantly increased in high-risk MDS group (p < 0.05), compared with low-risk MDS group which also had higher MVD than the control group (p < 0.05). Positive correlation was found between apoptosis of CD34(+) cells and SDF-1 levels in low-risk group, and SDF-1 level and MVD in high-risk group. It is concluded that the expression of SDF-1, apoptosis of BM CD34(+) cells and MVD were significantly abnormal in MDS patients, especially in different risk group, suggesting that SDF-1 level is related to cell apoptosis and angiogenesis.
    Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology 12/2011; 19(6):1438-42.
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    ABSTRACT: The aim of this study was to investigate the effect of haploidentical allogeneic bone marrow or peripheral blood hematopoietic stem cell transplantation (allo-HSCT) combined with umbilical cord blood mesenchymal stem cell (MSC) infusion in treatment of severe aplastic anemia (SAA). Five SAA patients received haploidentical allo-HSCT combined MSC infusion. HSC and MSC were collected from bone marrow or peripheral blood of haploidentical donors and umbilical cord blood respectively. After transplantation, the clinical hematopoietic reconstitution and early complications were monitored. The results indicated that all the 5 patients achieved hematopoietic reconstitution. The average time for WBC count > 2×10(9)/L was 13.8 days, and average time for Plt level > 20×10(9)/L was 17.8 days. The STR-PCR detection of patient peripheral blood at day 30 after transplantation showed that engraftment was complete donor's gene type. The communication with 1 patient was broken off because of his epillpsy, other 4 patients are all alive in diseases-free state. In conclusion, the haploidentical allo-HSCT combined with umbilical cord MSC infusion is an effective approach to cure SAA, which needs to be further studied in a large number of cases.
    Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology 10/2011; 19(5):1241-5.
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    ABSTRACT: This study was aimed to investigate the role of sequence similar matching (SSM) method in prediction of GVHD after HLA unmatched allogeneic hematopoietic stem cell transplantation (allo-HSCT). The data from 23 patients undergoing HLA unmatched allo-HSCT were analyzed and calculated by SSM method. The results showed that the incidence of acute and severe GVHD were significantly less in the allo-HSCT cases with total SSM value less than 55. In conclusion, the SSM method can be used to predict GVHD in the HLA-unmatched allogeneic hematopoietic stem cell transplantation.
    Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology 06/2010; 18(3):740-3.
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    ABSTRACT: This study was aimed to explore the value of dual-color dual-fusion fluorescence in situ hybridization (DC-DF-FISH) for the detection of bcr/abl fusion gene in chronic myeloid leukemia (CML). The karyotypes of chromosomes and bcr/abl fusion gene in 41 cases of CML including 18 cases of de-novo CML, 18 treated CML cases and 5 cases of CML received PBSCT were detected by conventional R-banding technique, DC-DF-FISH and RT-PCR. The results indicated that the Ph chromosome was found in 17 out of 18 cases of de novo CML by R-banding technique, with positive rate of 94.4%; DC-DF-FISH detection showed same result (94.4%). The R-banding technique was adopted to detect 18 treated patients and showed that 14 cases had metaphase for analysis, the Ph chromosome existed in 11 out of 14 cases with positive rate of 78.6% (11/14), however, DC-DF-FISH detection also showed positive rate of 94.4% (17/18) for these treated patients. The Ph chromosome in 5 cases after PBSCT did not found by R-banding technique, meanwhile FISH detection indicated that 1 case had bcr/abl gene, RT-PCR assay confirmed the result of FISH detection. It is concluded that the DC-DF-FISH technique is an accurate and reliable method for detecting bcr/abl gene which can be used in diagnosis of CML, evaluation of therapeutic efficacy and detection of minimal residual disease.
    Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology 05/2009; 17(2):261-5.
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    ABSTRACT: This study was aimed to investigate the chimerism and fusion gene expression in patients with CML after allo-HSCT, to analyse engraftment and minimal residual disease by using STR-PCR combined with RT-PCR qualitative and quantitative assays, and to evaluate their clinical value for predicting disease relapse. 4 relapsed patients with CML after allo-HSCT were dynamically investigated. Qualitative analysis of donor chimerism was performed by multiplex PCR amplification of STR markers and capillary electrophoresis with fluorescence detection, qualitative detection of bcr/abl transcripts was performed by RT-PCR. The results showed that the 100% donor chimerism appeared in 4 patients on day 28 after transplantation and bcr/abl expression was negative, but the 4 patients were in status of unstable mixed chimerism (DC: 0% - 80.4%) at the different time points during the following up with bcr/abl gene positive. 2 patients of them were continuously mixed chimerism after relapse of CML, the other 2 changed from MC to CC by intervention of clinical treatment. Decreasing values of donor chimerism were detected prior to the occurrence of graft rejection and CML relapse, and bcr/abl gene expression was positive. It is concluded that the results of STR-PCR in the range of its sensitivity fully correspond with bcr/abl tests in patients. The combination of STR-PCR with RT-PCR will provide a highly sensitive and valuable tool for evaluating engraftment, graft rejection, and relapse and predicting GVHD. Furthermore, it can provide a basis for early intervention of clinical treatment, and can identify these high risk patients with molecular or cytogenetic relapse after allo-HSCT.
    Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology 09/2008; 16(4):833-7.
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    ABSTRACT: The myelodysplastic syndromes (MDS) include a diverse groups of clonal and potentially malignant bone marrow disorders. Evidences exist that microenvironment cells from MDS marrow show functional abnormalities, which may be relevant to the incidence of such a disease. Mesenchymal stem cells (MSCs) are a very important component of hematopoietic microenvironment. This study was supposed to investigate the biological characteristics and functions of MSC derived from patients with MDS in low-risk. MSCs from bone marrow samples of 11 low-risk MDS patients were isolated, cultured and expanded. Morphology, immunophenotype and osteoblasts differentiation were analyzed. Their capacity of proliferation and hematopoietic supporting in vitro were measured. A real-time quantitative reverse transcriptase polymerase chain reaction method (RQ RT-PCR) was used for detecting the expression levels of relative cytokines and chemokines in MSC. MSCs from healthy donors were used as controls. The results showed that the culture-expanded cells from MDS patients displayed a typical fibroblast-like morphology. Cells were positive for SH2 (CD105), SH3 (CD73), Thy-1 (CD90), while negative for CD34 and CD45. After induction, these cells could differentiate into osteoblasts. The proliferative ability of MSCs in MDS patients were not different from those of MSC isolated from normal bone marrow (p > 0.05), however, their capacity of hematopoietic supporting in vitro were significantly weaker (p < 0.05). RQ RT-PCR detection indicated that the SDF-1 gene expression level in MSCs of low-risk MDS patients was significantly higher than that in MSC derived from healthy donors (p < 0.01). It is concluded that the abnormal function of MSC influences the regulation of hemotopoiesis in the bone marrow microenvironment of MDS patients. It is worthy to further investigate the new clue in etiological mechanism and therapeutic strategies for MDS.
    Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology 09/2008; 16(4):813-8.
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    ABSTRACT: To investigate the distribution of killer immunoglobulin like receptor (KIR) gene in the Han population in north China and the impact of donor KIR and patient HLA genotypes on the outcome of HLA-identical sibling hematopoietic stem cell transplantation patients with hematological malignancy. Polymerase chain reaction with sequence-specific primers (PCR-SSP) was used to detect the KIR distribution of 150 healthy people and the KIR genotype of donor and HLA genotype of allogeneic stem cell transplantation recipients of 74 donor-recipient pairs, and a retrospective study was carried out to analyze the outcomes of 45 patients with various hematological malignancies who received non T-cell-depleted transplant from HLA-identical sibling donors, all the subjects being of Han nationality in north China. The gene frequencies of KIR2DL1, KIR2DL2, KIR2DL3, and KIR3DL1 were 100%, 20%, 100%, and 95% respectively. 96% of the allogeneic donors carried one of the 3 class I ligands of inhibitory KIR. 36 of the 45 (80%) donor-recipient HLA-identical sibling transplant pairs lacked recipient HLA ligand for donor KIR, among which 35 lacked recipient HLA ligand for donor KIR2DL1, 1 pair lacked that for KIR2DL2/2DL3, and 31 pairs lacked that for KIR3DL1. Cumulative incidence analysis of graft versus host disease (GVHD) in the patients undergoing HLA-identical sibling hematopoietic stem cell transplantation demonstrated that the incidence of severe acute GVHD (aGVHD) in the patients lacking HLA ligand for donor-inhibitory KIR2DL1 was 31%, significantly lower than that of the patients with HLA ligand for donor-inhibitory KIR2DL1 (70%, P = 0.029), and the incidence of severe aGVHD in the acute myeloid leukemia patients lacking HLA ligand for donor-inhibitory KIR and KIR2DL1 was 18%, significantly lower than that of the KIR compatible patients (75%, P = 0.03). Almost all Chinese of Han nationality in north China carry having one of the 3 known class I ligands of inhibitory KIR. KIR and KIR2DL1 mismatch is associated with lower aGVHD after HLA-identical sibling hematopoietic stem cell transplantation.
    Zhonghua yi xue za zhi 12/2007; 87(44):3111-4.
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    ABSTRACT: The aim of this study was to analyze chimerism, evaluate the status of engraftment and predict the outcome of allogeneic hematopoietic stem cell transplantation (allo-HSCT) by multiple short tandem repeat (STR) amplification using fluorescence labeling polymerase chain reaction (PCR) combined with capillary electrophoresis. Peripheral blood and bone marrow in 27 patients who received myeloablative allogenetic cell transplantation were collected before and after transplantation in different times. 10 and 7 different STR markers were co-amplified in a single reaction by using a commercial AmpF/STR Profiler Plus/Cofiler plus PCR amplification kits. Separation of the PCR products and fluorescence detection were performed by ABI prism 310 Genetic Analyzer with capillary electrophoresis. The Genescan and Genotype soft ware were used for size calling and quantification of peak areas. The formula to calculate donor chimerism values was based on the different allelic distribution type between donor and recipient. The results showed that donor chimerism was similar by the two methods. The median number of informative alleles was 6.3 (4 - 9) by Profiler Plus and 4.9 (2 - 6) by Cofiler Plus. The donor alleles appeared in 26 patients on day 28 post transplantation. One patient was not observed to appear donor alleles. 14 patients with 100% donor chimerism (DC) had stable engraftment and they still survive in free leukemia. 9 patients had unstable mixed chimerism (DC: 0% - 90.2%), and 5 of them relapsed after allo-HSCT, 6 patients died. Decrease of donor chimerism appeared prior to graft rejection and disease relapse. The incidence of GVHD was higher in group of full donor chimerism. It is concluded that dynamic monitoring donor chimerism by STR-PCR in combination with all auto-capillary electrophoresis is a valuable tool for predicting graft rejection, disease relapse and occurrence of GVHD, and provides a basis for early clinical intervention in the patients received allo-HSCT.
    Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology 05/2007; 15(2):337-41.

Publication Stats

2 Citations

Institutions

  • 2011–2013
    • Tianjin Medical University Cancer Institute and Hospital
      T’ien-ching-shih, Tianjin Shi, China
  • 2007–2012
    • 307 Hospital of the Chinese People's Liberation Army
      Peping, Beijing, China
  • 2007–2010
    • Chinese PLA General Hospital (301 Hospital)
      Peping, Beijing, China