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  • Zhong, Liye  (7)
  • 2005-2009  (7)
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  • 2005-2009  (7)
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  • 1
    Online Resource
    Online Resource
    American Society of Hematology ; 2008
    In:  Blood Vol. 112, No. 11 ( 2008-11-16), p. 5082-5082
    In: Blood, American Society of Hematology, Vol. 112, No. 11 ( 2008-11-16), p. 5082-5082
    Abstract: BACKGROUND & OBJECTIVE FMyelodysplastic syndromes (MDS) are among the most frequent hematologic malignancies. The diagnosis of MDS can be difficult, and there is a paucity of molecular markers. The pathophysiology is still largely unknown. Therefore, we investigated whether serum proteome profiling may serve as a noninvasive platform to discover novel molecular markers for MDS and establish the predictive models that may be of help to serologic diagnosis and classification of MDS. METHODS FSerum samples were collected from 14 MDS patients including to 8 Refractory anemia with excess blasts in transformation (RAEB) and 6 Refractory cytopenia with multilineage dysplasia (RCMD) and 18 non-MDS hematologic malignancies and 8 age- and sex-matched healthy subjects. Serum peptides were separated and purified with a purification kit of magnetic beads, using magnetic beads-based weak cation exchange chromatography (MB-WCX) and MB-IMAC Cu, bases on immobilized metal ion affinity chromatography on the surface of superparamagnetic microparticles. We generated serum proteome profiles by matrix-assisted laser desorption/ionization time of-flight mass spectrometry (MALDI-TOF- MS) and identified a profile that distinguishes MDS from non-MDS hematologic malignancies and healthy subjects. RESULTS FA totaI of 146 effective protein peaks were detected at the molecular range of 1.02 tO 10.25 ku, Among which 7 protein peaks were different significantly among MDS patients, non-MDS hematologic malignancies and healthy subjects (P & lt;0.05). There was also different for Peptide mass fingerprinting in MDS patients, and the samples were divided into two groups, which was identical with clinical classification about RAEB and RCMD, using 3-cross validation approach. There was significantly different expression protein between RCMD and RAEB patients, which was identified as a piece of fibrinogen peptide. The expressions of fibrinogen in RAEB subtype patients were higher than RCMD subtype patients. CONCLUSION F Using the MALDI-TOF-MS technique may help to identify serum proteomic biomarkers related to MDS. The predictive models can discriminate MDS patients from other hematologic malignancies and healthy people effectively and help to identify MDS clinical classification. The different expression of Fibrinogen between RAEB and RCMD may suggested heterogeneity of etiopathogenisis in different subtypeof MDS.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2008
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 2
    In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 1147-1147
    Abstract: Abstract 1147 Poster Board I-169 In the past twenty years, allogeneic hematopoietic stem cells transplantation (Allo-HSCT) has been accepted as the most effective treatment for many hematologic malignancies. However, the successful rate of allo-HSCT has been limited by transplantation-related mortality and malignancies relapse, no matter using traditional intensity conditioning or reduced-intensity conditioning. In this study, we presented ninety-two patients with hematopoietic malignancies received fludarabine combinasion with modified Bu/Cy (FABC) conditioning regimen before allogeneic hematopoietic stem cell transplantation. Ninety-two patients with hematological malignancies (58 males, 34 females) ranged in age from 14 to 50 (median 28) years. These patients were diagnosed with acute lymphoblastic leukemia (ALL, n=30), acute myelogenous leukemia(AML, n=24), chronic myelogenous leukemia (CML, n=33; CP, n=27; CML-AP, n=5; CML-BC, n=1), myelodysplastic syndrome ( MDS, n=3), chronic myelomonocytic leukemia (CMML, n=1), and one patient coexisted chronic myelomonocytic leukemia and T lymphoblast cell lymphoma. Fifty-five (59.8%) patients were at high risk. From June 2004 to October 2008, 92 patients gave their informed consent and received conditioning regimen with fludarabine-based modified Bu/Cy (FABC conditioning regimen) in allo-HSCT. The FABC regimen consist of cytarabine 2.0 g/ m2 on day -9, busulphan (Bu) 3.2 mg/kg per day for intravenous on days -8 to day-6, followed by cyclophosphamide (Cy) 60 mg/kg per day on days -5 and day-4, combined fludarabin 30 mg/m2 per day for three consecutive days, on days -6 to day-4, and Me-CCNU (1-(2-Chloroethyl)-3-(4-ethylnitrobiphenyl Cylohexyl4)-1- Nitrosourea) 250 mg/m2 on day -3. Graft-versus-host-disease(GVHD) prophylaxis consisted of cyclosporine A, short-term MTX and Mycophenolate Mofefil (MMF 1.0g/day, on d-8 to d-1). Anti-T-lymphocyte globulin (2.5 mg·kg-1·d -1, on d-3 to d-1) was added to patients with mismatched sibling or unrelated donors. Follow-up was performed on 30 December, 2008. Ninety-two patients engrafted successfully, the median time for ANC 〉 0.5×109/L was 12 (8 to 22) days, and for BPC 〉 20×109/L was 12 (7 -32) days. Detected by short tandem repeat (STR)-PCR, complete donor chimerism was comfirmed in all patients on day +21 or day+30. The incidence of acute GVHD was 25% (23/92), and grades 3 to 4 acute GVHD developed in 8 (8.7%) of 92 patients with in 100 days after HSCT. Chronic GVHD developed in 40(47.6%) of 84 patients who were alive more than 100 days after HSCT, and the incidence of extensive cGVHD was 35.7%(30/84). The transplant related mortality (TRM) was 19.6% (18/92), mainly from severe infection (n=7), acute or chronic GVHD (n=5), transplant associated-microangiopathy (n=2), diffusion alveolar hemorrhage (n=2), and post-transplant lymphoproliferative disorders (n=2). With a median follow-up of 16.2(1.5 to 54.5) months, 70 (76.1%) of the 92 patients were alive and 67(72.8%) were disease-free. The probabilities of OS at 1 year and 2 years was 80% and 72.5%, and DFS was 79.1% and 71.4%, respectively. These results suggest that the fludarabine-based modified Bu/Cy conditioning regimen (FABC) should reduce severe acute GVHD and accelerate hematopoietis resconsition without increasing chronic GVHD and lower leukemia relapse rates even in high-risk patients. Footnotes Corresponding author Disclosure No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2009
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 3
    Online Resource
    Online Resource
    American Society of Hematology ; 2005
    In:  Blood Vol. 106, No. 11 ( 2005-11-16), p. 4921-4921
    In: Blood, American Society of Hematology, Vol. 106, No. 11 ( 2005-11-16), p. 4921-4921
    Abstract: Introduction The myelodysplastic syndromes (MDS) comprise a heterogeneous group of clonal hematopoietic stem cell disorders, while, immunological abnormalities are frequently observed in patients with MDS[1]. Several reports [2,3] revealed that about 10% of MDS patients have clinical autoimmune disorders like skin vasculitis, rheumatic disease, or autoimmune hemolytic anemia. Furthermore, serological immunological abnormalities like hyper- or hypogammaglobulinemia, positivities of antinuclear antibody, positivities of direct Coombs test, or inverted CD4/8 ratios were found in 18–65% of patients with MDS. Recently immunosuppressive therapies including prednisolone, antithymocyte globulin, and cyclosporin A (CsA) are used to treat cytopenia in some patients with MDS. We reported four patients with MDS. Rearrangements of the TCR-beta genes were seen in these patients using RT-PCR and Genescan analysis (CDR 3 length analysis). Also they had skewed TCR usages using TCR repertoire analysis. Methods Two patients with refractory anemia(RA), two with refractory anemia with blasts(RAEB). four males from 41to 68 yearsold. Complementarity determining region 3(CDR3) of TCR Vβ with 24 variable region gene was amplified in peripheral blood mononuclear cells, which were drawn from five patients with myelodysplastic syndromes (MDS) using RT-PCR, to observe the expression of TCR Vβreceptoroire T cells, the PCR products were further analyzed by genescan to evaluating clonality of T cells (CDR 3 length analysis), and compare results with age-matched healthy donors and patients with graft versus host disease(GVHD). Results We found a significantly higher number of skewed Vb profiles in the MDS and GVHD patients compared with donors. In peripheral blood T cells, Only 2-11 Vb subfamily T cells could be identified in MDS patinets, clonal expansion T cells could be found in Vb1, 3,13, 14 and 21 subfamilies. Disussion In this study, we evaluated the total T-cell repertoire of 4 MDS patients using gendscan analysis to look for evidence of T-lymphocyte clonality. This analysis showed that all 4 patients exhibited extensive skewing of their TCR spectratypes, suggesting clonal or oligoclonal T-cell expansions. Epperson [10]also reported the same results. As we know, acute and chronic graft-versus-host disease(GVHD) is a major complication after allogeneic bone marrow transplantation. GVHD is mediated by T cells that are derived from the BM graft. In this study, we compared the results of GVHD patients with that of MDS patients, and found that these two groups patients show TCR Vb skew distribution and clonal expansion. These findings provide further evidence that T cell mediated immune processes are a feature of MDS.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2005
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 4
    Online Resource
    Online Resource
    American Society of Hematology ; 2009
    In:  Blood Vol. 114, No. 22 ( 2009-11-20), p. 4132-4132
    In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 4132-4132
    Abstract: Abstract 4132 The objective was to definite the expression level of aven mRNA of white blood cells from peripheral blood(PB)of de novo acute myeloid leukemia and preliminary analyze its clinical significance, providing a experimental basis for evaluating prognosis. Aven mRNA levels in PB samples from 69 AML patients were detected by using real-time quantitative PCR. The relation of aven mRNA level with clinical and hematological characteristics (age, sex, WBC, Hb, Plt, LDH, Blast% in PB and BM,FAB subtype) and treatment outcome (complete remission rate and relapse rate)were analyzed. Twenty-one normal individuals served as controls. The level of aven mRNA was between 11.72% and 178.93 %(median 37.2%) in de novo AML and between 10.81% and 50.98 %(median 28.81%) in normal individuals. Aven mRNA level was higher in the AML group than in the controls (p=0.006). When we compared aven mRNA with other clinical and hematological parameters, there were significant correlations between aven mRNA and age(r=0.25,p=0.039),aven mRNA and hemoglobin level (r=0.29,p=0.019),aven mRNA and FAB subtype(r=0.253,p=0.036). We found that median level of aven mRNA in group whose age older than median age was higher than group whose age younger than median level(p=0.018).The complete remission rate after two cycles chemotherapy in group with lower aven mRNA level(25/30,83.33%)was higher than group with higher aven mRNA level(21/30,70%). But the difference was not significant(p=0.22).The difference of aven mRNA expression level between AML patients with relapse and that without relapse was not significant (p=0.076). In conclusions, the level of aven mRNA in de novo AML is overexpression. The overexpression of aven mRNA is likely to play an important role in tumorigenesis of AML. Association of aven mRNA expression with treatment outcome and relapse was not observed. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2009
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 5
    Online Resource
    Online Resource
    American Society of Hematology ; 2009
    In:  Blood Vol. 114, No. 22 ( 2009-11-20), p. 4845-4845
    In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 4845-4845
    Abstract: Abstract 4845 To screen molecular markers for refractory anemia with excess blasts in transformation (RAEB) in myelodysplastic syndromes (MDS) by serum proteome profiling. Methods Serum protein were isolated respectively from patients with RAEB, acute myeloid leukemia or normal person by 2-dimensional electrophoresis(2-DE). The imaging films were obtained and the differential reacting protein spots were recognized. Then the differential reacting proteins were obtained in the replica gel by matching analysis,and identified by peptide mass fingerprint based on matrix-assisted laser desorption/ionization time of-flight mass spectrometry (MALDI-TOF-MS) and database searching. Results Seven differentially expressed proteins in RAEB were found by 2-DE. Of the 7 proteins, 4 were identified with significantly statistical difference, including dipeptidyl peptidase (DPP/CD26), polymerase (DNA directed) kappa, PRO2044 and albumin-like. Conclusion 2-DE-based serum proteome profile can help to identify serum proteomic biomarkers related to MDS. DDP/CD26 has increased serum levels in RAEB subtype MDS, suggesting significant action in advanced MDS. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2009
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
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  • 6
    Online Resource
    Online Resource
    American Society of Hematology ; 2009
    In:  Blood Vol. 114, No. 22 ( 2009-11-20), p. 4833-4833
    In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 4833-4833
    Abstract: Abstract 4833 Myelodysplastic syndromes (MDS) are clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis and frequent progression to acute myeloid leukemia. The pathophysiology of these syndromes remains poorly explained. The immune system also seems to contribute to the progressive cytopenias observed in MDS in some cases. We investigated the frequency and the discriminative value of TCR gamma and delta CDR3 clonality using RT-PCR and genescan technique in 40 MDS patients (24 male, 16 female),which included refractory anemia(n=1), refractory anemia with with ringed sideroblasts(n=6), refractory anemia with excess of blasts I (n=16)and II (n=17) respectively. The median age was 60 years (range 15-84).The results showed that 35(87.5%) MDS patients expressed all three TCR Vgamma subfamilies. Four(10%) and one(2.5%) MDS patients expressed two and one TCR Vgamma subfamilies respectively. Clonal expansion of T cells in some Vgamma subfamilies could be identified in 31 patients. The clonal expansion of Vgamma2 subfamily were identified most frequently. All the Vdelta subfamilies were absent in 2 MDS patients. The remaining 38 (95%) MDS cases expressed 0-6 Vdelta subfamilies. Vdelta1 and Vdelta2 were expressed most frequently followed by Vdelta8. While only 3(7.5%) patients expressed Vdelta5 subfamilies. Clonal expansion of Vdelta T cells were found in all MDS patients. The most frequent clonal expansion T cell was Vdelta3. In addition, 12 patients expressed monoclonal T cell Vdelta subfamily. Monoclonal expanded T cells were found in Vdelta3, Vdelta4, Vdelta6, Vdelta7 and Vdelta8 subfamilies. In summary,we found that MDS patients showed TCR Vgamma and delta skew distribution and clonal expansion. The absent of TCR Vdelta subfamily was more evident than TCR Vgamma subfamily. These findings provided further evidence that T cell mediated immune processes were a feature of MDS. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2009
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 7
    In: Blood, American Society of Hematology, Vol. 110, No. 11 ( 2007-11-16), p. 4970-4970
    Abstract: Macrophage activation syndrome (MAS) /Hemophagocytic syndrome (HPS) is characterized by proliferation of activated macrophages under conditions such as infection(C Clin Infect Dis 2004)lymphoma(Aouba A Am J Hematol 2004), autoimmune disease(Kaneko K Clin Rheumatol 2005), solid organ transplantation(Akamatsu N,Transplant Proc 2006;). There have been several reports of MAS /HPS after hematopoietic stem cell transplantation, involving not only allogeneic,but also autologous transplantation(Sreedharan A Bone Marrow Transplantation,2006). Generally, MAS /HPS is a cytokine-related disorder.But at present, its clinical characteristics remain unknown. We firstly study here the T-cell receptor repertoire diversity and flow cytometric analysis in MAS /HPS after unrelated peripheral blood stem cell transplantation. The CDR3 of TCR Vα and Vβ subfamily genes were amplified in peripheral blood mononuclear cells from the patient with MAS/HPS after unrelated peripheral blood stem cell using RT-PCR for detection of the distribution of TCR Vα and Vβ repertoire, the PCR products were further analyzed by genescan technique for the CDR3 size, to evaluating clonality of the detectable TCR Vα and VβT cells. Lymphocyte subsets in the peripheral blood were detected by monoclone antibody and flow cytometry including T lymphocyte subsets and NK cells. Flow-cytometric analysis showed CD56+ CD16+ cell 68.65% and CD3+ cell 11.79% in the lymphocyte population;CD16+CD69+ cell 68.51% and CD25+CD16+ cell 31.59% in NK cell. In the T lymphocytic subsets, CD25 + CD3+ cell 62%; CD69+CD3+ cell 75.81%; CD25CD4+ cell 0.81%,CD25CD8+ cell 3.48%; CD69CD4+ cell 0.31%, CD69+CD8+ cell 16.86%.The results show that the main activated lymphocytes is NK cell in patient at diagnosed with MAS/HPS. Of interest, it was only after the addition of high-dose IVIG 1g/kg/d for two days (Ostronoff et al BMT2006) to the treatment that MAS remitted. There are 23 Vα and 15Vβ subfamily T cells could be identified in this time, and the clonal expansion T cells could be found in TCR Vα5, 13, 20; TCR Vβ4, 11, 15 and 21subfamilies. Billiau et al (Blood 2005)describes the immunohistochemical findings on liver tissues from 5 children with MAS in the context of a different type of hemophagocytic syndrome (HPS) in liver transplantation. This study is the first directly to substantiates the presumed immunopathogenesis of MAS by documenting in situ expression of IFN-γ+ by activated CD8+ lymphocytes, and of IL-6 and TNF-α+ by hemophagocytosing macrophages, on liver tissues of patients with MAS. We found no evidence of potential infectious, autoimmune or malignant triggers of R-HPS in our patient, despite extensive investigations. We conclued that the skew distribution and clonal expansion of TCR Vα and Vβ subfamily T cells underscore the primary role of T cells in the pathogenesis of MAS/HPS.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2007
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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