1.Advance of Research on the Immunotherapy Targeting B Cell Maration Antigen for Multiple Myeloma--Review.
Chun-Yan LUAN ; Zi-Ying JIAN ; Tao CHENG ; Bao-An CHEN
Journal of Experimental Hematology 2019;27(5):1701-1705
Abstract B cell maturation antigen (BCMA) is an ideal target for precise treatment due to its highly selective expression on malignant myeloma cells. This review summarizes briefly the advances in the latest research progress on biological activity of BCMA, its significance as a biomarker and immunotherapy direcited against BCMA, such as bispecific antibodies, antibody drug conjugates, chimeric antigen receptor T cell therapy against mature B cell antigens.
Antigens, Differentiation, B-Lymphocyte
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B-Cell Maturation Antigen
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B-Lymphocytes
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Humans
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Immunotherapy
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Multiple Myeloma
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therapy
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T-Lymphocytes
2.Effect of SAHA on Maturation of Dendritic Cells and Its Mechanism.
Ming-Ming FU ; Chun-Yang BAI ; Yu-Han CHEN ; Jin-Zong LIN ; Jing-Yuan LU ; Zhao WANG ; Yong-Li ZHANG
Journal of Experimental Hematology 2015;23(3):821-825
<b>OBJECTIVEb>To investigate the effect of SAHA on the maturation of human dendritic cells (DC) and to explore its underlying mechanism.
<b>METHODSb>Peripheral blood mononuclear cells (PBMNC) were isolated from human peripheral blood and cultured in RPMI 1640 medium with 100 ng/ml rhGM-CSF and 500 U/ml rhIL-4. In the LPS induced maturation process, dendritic cells treated with or without SAHA were used as test group, and dendritic cells treated without LPS or SAHA were used as control group. DC was observed under inverted microscope. Flow cytometer was used to detect the surface antigen molecules expressed by DC. The mixed lymphocyte culture (MLC) was used to observe the allogeneic lymphocyte stimulation. The NF-κB signaling pathway was detected by electrophoretic mobility shift assay (EMSA).
<b>RESULTSb>The SAHA could effectively suppress the maturation of DC induced by LPS, the DC treated with SAHA+LPS had immature morphological characteristics; the expression of CD80, CD83 and HLA-DR in SAHA+LPS group and control group were significantly down-regulated as compared with single LPS group (P<0.01); the ability of DC to stimulate the proliferation of allogeneic T lymphocytes in SAHA+LPS group and control group was significantly weaker than that in single LPS group (P<0.01); EMSA results showed that NF-κB activity decreased after SAHA and LPS treatment and was significantly lower than that of single LPS group.
<b>CONCLUSIONb>SAHA can effectively suppress DC maturation induced by LPS and also weaken the ability to stimulate allogeneic T lymphocyte. NF-κB signaling pathway is involved in regulating DC maturation.
Cell Differentiation ; Dendritic Cells ; Flow Cytometry ; HLA-DR Antigens ; Humans ; Lymphocyte Activation ; Lymphocyte Culture Test, Mixed ; NF-kappa B ; T-Lymphocytes
3.Flow cytometric immunophenotyping in fine-needle aspiration of lymph nodes.
Jae Gul CHUNG ; Gyung Yub GONG ; Joo Ryung HUH ; Shin Kwang KHANG ; Jae Y RO
Journal of Korean Medical Science 1999;14(4):393-400
Fine-needle aspiration (FNA) of lymph nodes has been regarded as a useful method in the diagnosis of lymphadenopathy. However, this procedure has been shown to be of limited value in the diagnosis of low or intermediate grade malignant lymphomas in some studies. Immunophenotyping is an essential adjunct to cytomorphology for the diagnosis of lymphoma by FNA. Immunophenotyping using flow cytometry (FCM) is rapid, objective and reliable. Using FCM, multiparametric analysis of 33 FNA materials from lymph nodes was performed and profiles of surface markers of lymphoid cells were assessed. In reactive hyperplasia, patterns of cell surface markers were quite variable, but disclosed polyclonality. Most of the B-cell lymphomas showed immunophenotypes for B-cell lineages with their kappa: lambda or lambda: kappa ratio being over 3:1. In T-cell lymphomas, T-cell surface markers were predominantly expressed as well. In conclusion, our results suggest that immunophenotyping of lymph node aspirates is a valuable diagnostic adjunct for lymphoproliferative disorders, particularly in B-cell lymphomas because immunophenotyping can be easily and adequately performed by FCM.
Antigens, CD19/analysis
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Antigens, CD20/analysis
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Antigens, CD3/analysis
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Antigens, CD4/analysis
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Antigens, CD5/analysis
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Antigens, CD7/analysis
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Antigens, CD8/analysis
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B-Lymphocytes/immunology
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B-Lymphocytes/chemistry
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Biopsy, Needle
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Flow Cytometry/methods*
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Hodgkin Disease/pathology
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Human
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Immunophenotyping
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Lymph Nodes/pathology
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Lymph Nodes/chemistry
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Lymphatic Diseases/pathology*
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Lymphatic Metastasis/pathology
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Lymphoma, B-Cell/pathology*
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Lymphoma, Non-Hodgkin/pathology
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T-Lymphocytes/immunology
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T-Lymphocytes/chemistryt
4.Study on the immunophenotypes of bone marrow cells from patients with myelodysplastic syndromes and its clinical implications.
Jian-Ying WANG ; Xiao-Ming LI ; Fa-Ju LI ; Xin-Gui CHEN
Journal of Experimental Hematology 2002;10(2):173-174
The phenotypes of the bone marrow cells in various subtypes of myelodysplastic syndromes (MDS) and its clinical implication were explored. The antigen expression of a panel of antigens expressed in marrow cells from 30 patients with subtypes of MDS was assayed by alkaline phosphatase anti-alkaline phosphatase method. The results showed that the expression of myeloid antigens appeared abnormality, CD13 and CD33, found on granulocyte and macrophage precursors, increased, and CD15 decreased. There were no significant changes for monocytic antigen CD14 and lymphoid antigens CD7 and CD10. CD34 was increased in RAEB/RAEB-t and was not increased in RA/RAS patients. CD71, expressed by erythroblast and proliferative cells, was higher in all subtypes of MDS than that in control group. It is suggested that the bone marrow cells from MDS patients showed abnormality of more than two series of immunophenotypes, detection of immunophenotype in MDS cells might be contributed to the diagnosis and predicting prognosis.
Adult
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Aged
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Antigens, CD
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analysis
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Antigens, CD34
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analysis
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Antigens, CD7
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analysis
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Antigens, Differentiation, B-Lymphocyte
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analysis
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Antigens, Differentiation, Myelomonocytic
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analysis
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Bone Marrow Cells
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immunology
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CD13 Antigens
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analysis
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Female
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Humans
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Immunophenotyping
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Lewis X Antigen
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analysis
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Lipopolysaccharide Receptors
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analysis
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Male
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Middle Aged
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Myelodysplastic Syndromes
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immunology
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pathology
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Neprilysin
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analysis
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Receptors, Transferrin
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Sialic Acid Binding Ig-like Lectin 3
5.Evaluation of the subsets of lymphocytes and their activated status in patients with myelodysplastic syndrome.
Jun YANG ; Chun WANG ; Kuang-Cheng XIE ; Shi-Ke YAN ; Yan-Rong GAO ; Qi CAI ; You-Wen QIN ; Li-Ping WAN ; Yu CAI
Journal of Experimental Hematology 2006;14(4):708-713
This study was purposed to investigate the clinical significance of the amount and activated status of T cell subsets, B cells, NK cells in peripheral blood from patients with myelodysplastic syndrome (MDS). The proportion of T cells, B cells, NK cells in peripheral blood from 30 patients with MDS and their surface activation markers of CD28, CD45RA, CD45RO, CD69, HLA-DR were analyzed by flow cytometry. Twenty-two patients were in the low risk group (RA + RAS) while eight patients were in the high risk group (RAEB + RAEBT). The result showed that the amounts of T cells (CD3+ cells) in peripheral blood from patients with MDS were lower than those in control group. The amounts of naive CD4+ cells (CD4+ CD45RA+ cells) in MDS patients were lower than those in control. The expression rates of early activation marker (CD69) and late activation marker (HLA-DR) on CD3+ cells in MDS patients were significantly higher than those in control. The abnormalities of the immunologically competent cells were mainly observed in the low risk group (RA + RAS), and were characterized by the high expression rates of CD69+ and HLA-DR+ on CD3+ cells, the decrease of B cell amounts. The amount abnormalities of T cell subsets were mainly observed in high risk group (RAEB + RAEBT), and were characterized by the decrease of CD3+ cells and CD3+ CD4+ CD8- cells (Th cells) amounts without high expression of the CD69 and HLA-DR, the decrease of NK cells amounts. It is concluded that there are the abnormalities of T cell subsets and function in the patients with MDS and may change with disease progression, so the measurement of amount and activated status of T cell subsets in peripheral blood from MDS patients can have predictive role for diagnosis of disease progression and guide of therapy.
Adolescent
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Adult
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Aged
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Aged, 80 and over
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Antigens, CD
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immunology
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Antigens, Differentiation, T-Lymphocyte
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immunology
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B-Lymphocytes
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immunology
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CD3 Complex
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immunology
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Female
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HLA-DR Antigens
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immunology
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Humans
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Killer Cells, Natural
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immunology
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Lectins, C-Type
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Lymphocyte Activation
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immunology
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Male
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Middle Aged
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Myelodysplastic Syndromes
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immunology
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T-Lymphocyte Subsets
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immunology
7.Comparative study on dendritic cells stimulated with HBsAg or HBcAg in patients with chronic hepatitis B.
Peng KANG ; Shu-Lan LUO ; Shu-Chen LI
Chinese Journal of Experimental and Clinical Virology 2007;21(3):250-252
<b>OBJECTIVEb>To study activation of dendritic cells (DC) isolated from peripheral blood monocytes of patients with chronic hepatitis B after stimulation with HBsAg or HBcAg.
<b>METHODSb>DCs were isolated from peripheral blood monocytes of patients with chronic hepatitis B. DCs were impulsed with HBsAg and HBcAg separately before their maturation. The expression levels of DC surface molecule were analyzed by using flow cytometry and the ability of DC to induce T lymphocyte proliferation was evaluated by a liquid scintillation counter and the amount of interleukin-12 (IL-12) in mixed lymphocytic (IL-12) in mixed lymphocytic reaction (MLR) was measured by using ELISA.
<b>RESULTSb>The expression rate of CD86 significantly increased to (29.20 +/- 5.18)% on DC after loading with HBcAg as compared with those after loading with HBsAg (76.19 +/- 3.90)% and controls (62.37 +/- 4.24)%, P>0.01. The ability of DC after loading with HBcAg to induce T lymphocyte proliferation (34,326 +/- 3088 cpm) was significantly higher than that of DC after loading with HBsAg (20,306 +/- 2897 cpm) and controls (3454 +/- 409 cpm), P greater than 0.01. The amount of IL-12 in MLR of DC after loading with HBcAg was (348 +/- 42.8) ng/L, which was significantly higher than those of DC after loading with HBsAg (226 +/- 30.6) ng/L and controls (116 +/- 15.6) ng/L, P greater than 0.01.
<b>CONCLUSIONb>Human dendritic cell stimulated with HBcAg could more efficiently present antigen and induce specific T cell immune response.
Adult ; Antigens, CD ; metabolism ; Antigens, Differentiation, Myelomonocytic ; metabolism ; Cell Proliferation ; Dendritic Cells ; cytology ; immunology ; metabolism ; Female ; Flow Cytometry ; Hepatitis B Core Antigens ; immunology ; Hepatitis B Surface Antigens ; immunology ; Hepatitis B, Chronic ; blood ; virology ; Humans ; Lymphocyte Activation ; immunology ; Male ; Middle Aged ; T-Lymphocytes ; cytology ; immunology ; Young Adult
8.Role of costimulatory signals in idiopathic thrombocytopenia purpura: review.
Xiao-Lin ZHANG ; Jun PENG ; Ming HOU
Journal of Experimental Hematology 2006;14(5):1053-1055
Idiopathic thrombocytopenia purpura (ITP) is an autoimmune disease which is characterized by destruction of platelets by macrophages in the reticuloendothelial system. Recent studies suggest that ITP is related to the abnormal activation and apoptosis of T/B cells which lead to failure of immune tolerance. Now it is becoming clear that costimulatory signals are required for full T/B cell activation and assumed to modulate T/B cells responses as well as other aspects of the immune system. This review focuses on the role and state-of-the-art advancements of costimulatory signals in ITP.
Antigens, CD
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immunology
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Antigens, Differentiation
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immunology
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Antigens, Differentiation, T-Lymphocyte
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immunology
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B-Lymphocytes
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immunology
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CD28 Antigens
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immunology
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CTLA-4 Antigen
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Humans
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Immune Tolerance
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Inducible T-Cell Co-Stimulator Protein
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Purpura, Thrombocytopenic, Idiopathic
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immunology
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Receptors, Tumor Necrosis Factor
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immunology
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Signal Transduction
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physiology
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T-Lymphocytes
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immunology
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physiology
9.A clinicopathologic study on the diffuse malignant lymphoma: a morphologic and immunophenotypic analysis in 62 patients at Harbor-UCLA Medical Center.
Ju Hie LEE ; Nora CJ SUN ; Walid SALAHI ; Hong CHEN ; Moon Ho YANG
Journal of Korean Medical Science 1992;7(3):204-313
In order to compare the prognoses of patients with diffuse malignant lymphomas on the basis of histology and immunophenotypes, we retrospectively studied 62 cases of diffuse lymphoma arising in lymph nodes. We also evaluated the reactivity patterns of monoclonal antibodies (MoAb) LN1, LN2 and LN3 to determine the criteria for making a differential diagnosis in B cell lymphomas. The immunologic phenotypes were determined by the avidin biotin peroxidase complex method, using frozen or paraffin fixed tissues. The majority (66.3%) were B cell with the remaining 20.9% being T cell and 12.9% were non-B, non-T cell lineage. Immunological heterogeneity was found especially in the mixed small and large cell and the immunoblastic lymphomas. There was no significant difference between B- and T-cell lymphomas with respect to survival and death (P > 0.05). Histologically 79% (49/62) of the lymphoma was large cell and 21% (13/62), small cell lymphoma. There was a difference in prognosis between low, intermediate and high-grade of lymphomas. However there were no significant differences among the subtypes of the diffuse aggressive lymphomas. Factors associated with poor prognosis were advanced stages (P < 0.025) and histology of the malignant lymphomas. MoAb LN1, LN2 and LN3 gave positive staining in 83.3%, 91.7% and 60% of B cell lymphomas, respectively. The most common phenotypic pattern in B cell lymphomas was LN1+, LN2+, LN3+/-, suggestive of follicular center cell origin. As a panel, phenotypic patterns of MoAb LN1, LN2 and LN3 may be useful in differentiation of follicular center cell lymphoma from others.
Adolescent
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Adult
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Aged
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Aged, 80 and over
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Antigens, CD/biosynthesis
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Antigens, Differentiation, B-Lymphocyte/biosynthesis
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Child
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Female
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Follow-Up Studies
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Histocompatibility Antigens Class II/biosynthesis
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Humans
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Immunoenzyme Techniques
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Immunophenotyping
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Lymphoma, B-Cell/immunology
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Lymphoma, Non-Hodgkin/immunology/*pathology
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Male
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Middle Aged
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Neoplasm Staging
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Prognosis
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Sialyltransferases/biosynthesis
10.Detection of cytoplasmic antigens by flow cytometry and its implication for leukemia immunophenotyping.
Yan-Rong LIU ; Hong YU ; Yan CHANG ; Shan-Shan CHEN
Journal of Experimental Hematology 2002;10(1):17-21
The purpose of this study was to optimize a fixation procedure for detection of cytoplasmic antigens by flow cytometry(FCM) and to evaluate the effect of intracellular CD3, CD22, CD79a and myeloperoxidase(MPO) in lineage assignment. Four kinds of fixation procedure and three or four color direct immunofluorescence staining were used to permeate cell membrane and label cell surface and intracellular antigens by means of FCM. Results showed that percentage of cytoplasmic antigens positive cells was the highest and cell scatter and fluorescence intensity of CD45 were not changed after using of FACS permeabilization solution. MPO protein was positive in 16/18 acute myeloid leukemia(AML) patients. 4 cases of T cell-acute lymphoblastic leukemia (T-ALL) cases were positive for cytoplasmic CD3(c CD3) but surface CD3 was negative. c CD22 was only detected in 9/13 of B-ALL and cCD79a was positive in 5/5 B-ALL. 18/38 cases of acute leukemia were expressed in more than one lineage marker, 8/21 cases of acute non-lymphocytic leukemia(ANLL) were CD7 positive. 7/17 cases of acute lymphocytic leukemia (ALL) expressed CD13. After further cytoplasmic antigen detection, one was considered to be a T/myeloid biphenotypic leukemia, another one was diagnosed as biclonal or mixed leukemia. The results suggest that intracellular CD3,CD22,CD79a and MPO are lineage specific markers, they are very important for biphenotypic and biclonal/mixed acute leukemia identification
Adolescent
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Adult
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Aged
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Aged, 80 and over
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Antigens, CD
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analysis
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biosynthesis
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Antigens, Differentiation, B-Lymphocyte
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biosynthesis
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CD3 Complex
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biosynthesis
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CD79 Antigens
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Cell Adhesion Molecules
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Child
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Child, Preschool
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Diagnostic Techniques and Procedures
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Female
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Flow Cytometry
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Humans
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Immunophenotyping
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methods
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Lectins
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biosynthesis
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Leukemia
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classification
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pathology
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Male
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Middle Aged
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Peroxidase
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biosynthesis
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Receptors, Antigen, B-Cell
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biosynthesis
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Sialic Acid Binding Ig-like Lectin 2