Abstract:
BACKGROUND:In patients treated with rituximab and alemtuzumab for lymphomas or CLL, antibody-dependent cellular cytotoxicity (ADCC) is a major mechanism of action. Therefore, assessment of ADCC is mandatory to understand the complex mechanisms leading to the anti-lymphoma effects of monoclonal antibodies (mAb). Due to methodical difficulties, little is yet known about the relevant cell subpopulations and effector mechanisms leading to tumor lysis in ADCC. METHODS:We used a novel flow cytometric assay that detects CD107a as a marker for NK-cell degranulation to characterize and quantify peripheral blood natural killer (NK) cells mediating ADCC in vitro and in vivo. RESULTS:We observed specific and dose-dependent NK-cell activation after administration of rituximab and alemtuzumab. The number of degranulating NK cells was closely related to the concentration of mAb and the effector:target ratio. We were able to quantify and characterize the peripheral blood NK cells mediating ADCC. The majority of degranulating NK cells had the phenotype: CD56(dim), CD69(+), NKG2D(+), NKp30(-), NKp46(-), and CD94(-). Furthermore, we found that the CD107a assay can also visualize ADCC under clinical conditions as we observed increased numbers of NK cells degranulating in response to CD20(+) lymphoma cell lines in patients with non-Hodgkin's lymphoma treated with rituximab. CONCLUSIONS:We were able to quantify and characterize NK cells mediating ADCC with a new and feasible method. The CD107a assay may be useful for predicting treatment responses of individual patients and may help find the optimal dosage and timing for treatment with mAb.
journal_name
Exp Hematoljournal_title
Experimental hematologyauthors
Fischer L,Penack O,Gentilini C,Nogai A,Muessig A,Thiel E,Uharek Ldoi
10.1016/j.exphem.2006.02.015subject
Has Abstractpub_date
2006-06-01 00:00:00pages
753-9issue
6eissn
0301-472Xissn
1873-2399pii
S0301-472X(06)00121-4journal_volume
34pub_type
杂志文章abstract::Pretreatment of mice with 5-fluorouracil (5-FU) depletes total marrow cellularity but leaves a residual population of cells with enhanced regenerative capability. Using the long-term Dexter liquid culture system, we studied the effects of 5-FU on murine marrow cells and their production of pluripotent stem cells (CFU-...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1986-03-01 00:00:00
abstract::A useful cytochemical technique has been developed which facilitates the identification of the types of cell aggregates which proliferate in soft agar cultures of hematopoietic stem cells. Staining of fixed agar discs for alpha-naphthyl acetate esterase (ANAE), naphthol AS-D chloroacetate esterase (CAE) and with Luxol...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1983-01-01 00:00:00
abstract:OBJECTIVE:New nonmyeloablative strategies to improve acceptance of mismatched bone marrow (BM) may compensate for the inadequate supply of compatible grafts. Recently we proposed to facilitate engraftment of mismatched BM by selective depletion of activated donor-reactive host cells with cyclophosphamide (CY). Here we ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2004.07.017
更新日期:2004-11-01 00:00:00
abstract:OBJECTIVE:To test gibbon ape leukemia virus (GALV) pseudotype vector transduction of marrow subpopulations that contribute to hematopoietic reconstitution in vivo. MATERIALS AND METHODS:Autologous CD34(+) Lin(-), CD34(+) Lin(+), and CD34(-) Lin(-) marrow cells, transduced by coculture with PG13/LN, PG13/LNX, and PG13/...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(00)00137-5
更新日期:2000-05-01 00:00:00
abstract:UNLABELLED:OBJECTIVE, METHODS, AND RESULTS: To reduce the period of posttransplant neutropenia and related early morbidity and mortality of cord blood (CB) transplants, we assessed the feasibility of co-infusion of a low number of highly purified peripheral blood CD34+ cells from a related haploidentical donor with a C...
journal_title:Experimental hematology
pub_type: 临床试验,杂志文章
doi:10.1016/s0301-472x(03)00067-5
更新日期:2003-06-01 00:00:00
abstract:OBJECTIVE:Recruitment of endothelial progenitor cells to the sites of ischemia has recently been suggested as a mechanism of tissue repair. Here we address the hypothesis that the hypoxia-inducible full-length endothelial-monocyte-activating polypeptide II (EMAP II) provides a mechanism to recruit late outgrowth highly...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2006.05.021
更新日期:2006-08-01 00:00:00
abstract:OBJECTIVE:B-lineage acute lymphoblastic leukemia (ALL) and chronic myeloid leukemia in lymphatic blastic phase in adults have poor prognoses despite intensive chemotherapy. Novel targeted treatment modalities emerge, but their evaluation requires relevant in vitro models of lymphoblastic leukemia. Presently available c...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2008.11.002
更新日期:2009-03-01 00:00:00
abstract::This study is about enrichment of hemopoietic stem cell concentration in mouse bone marrow by use of a glass wool filtration technique. Maximum stem cell concentration was accomplished when filtration conditions were as follows: (1) support medium supplemented to 15% with fresh serum from syngeneic donors; (2) no incu...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1977-01-01 00:00:00
abstract::Leukemia associated inhibitor, LAI, reversibly inhibits DNA synthesis in normal human granulocyte-macrophage colony-forming units (CFU-GM). LAI is produced by myeloid leukemia cells, a subpopulation of normal nonadherent low-density mononuclear cells in peripheral blood and bone marrow, as well as by the human promyel...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1987-12-01 00:00:00
abstract::Telomeres cap chromosomal ends and are shortened throughout a lifetime. Additional telomere erosion has been documented during conventional chemotherapy or hematopoietic stem cell transplantation. Previous studies of stem cell transplantation reported variable amounts of telomere shortening with inconsistent results r...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2007.08.028
更新日期:2008-01-01 00:00:00
abstract::Mammalian erythroblasts undergo enucleation through a process thought to be similar to cytokinesis. Microtubule-organizing centers (MTOCs) mediate organization of the mitotic spindle apparatus that separates the chromosomes during mitosis and are known to be crucial for proper cytokinesis. However, the role of MTOCs i...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2015.12.003
更新日期:2016-04-01 00:00:00
abstract::Anamorsin (AM) is an antiapoptotic molecule that confers factor-independent survival on hematopoietic cells. AM-deficient (AM(-/-)) mice are embryonic lethal because of a defect in definitive hematopoiesis; however, the significance of AM in embryonic hematopoiesis remains unknown. This study characterized the hematop...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2014.01.002
更新日期:2014-05-01 00:00:00
abstract::Colony formation by megakaryocyte (MK) progenitors was studied in 36 normal individuals and in 26 patients with primary thrombocythemia (PT) using an improved plasma clot cloning system. MK colonies were identified by immunoperoxidase staining using a monoclonal antibody against human platelet glycoprotein IIb/IIIa co...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1989-01-01 00:00:00
abstract::Fanconi anemia (FA) is a rare recessive disease characterized by progressive bone marrow failure, congenital abnormalities, and increased incidence of cancers. To date, mutations in 22 genes can cause FA or an FA-like phenotype. In China, in addition to clinical information, FA diagnosis primarily relies on genetic se...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2018.07.003
更新日期:2018-10-01 00:00:00
abstract::Lymphatic leukemia L1210-bearing semisyngeneic Balb/c x DBA/2Wf F1 (CD2F1) mice were subjected to chemoradiotherapy (2 x 100 mg/kg of cyclophosphamide i.p. and 1000 cGy of total body irradiation) and reconstitution with 10(7) syngeneic bone marrow cells i.v. The bone marrow obtained from leukemic mice was previously e...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1988-10-01 00:00:00
abstract::The effect of indomethacin (6 mg/kg daily orally for 2, 3 or 4 days) on myelopoiesis was studied in mice by estimating 1) differential cell counts of bone marrow, 2) proliferation of the CFUC in presence of GM-CSF, 3) proliferative state of CFUC after tritiated thymidine suicide. After 4 days of treatment, a rise in t...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1980-10-01 00:00:00
abstract::Initially described as an endogenous inhibitor of proteases, the tissue inhibitor of metalloproteinases 1 (TIMP-1) also displays cytokine-like functions. TIMP-1 is a soluble protein whose levels are increased under inflammatory conditions. We recently found that TIMP-1(-/-) mice have decreased bone marrow (BM) cellula...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2015.07.003
更新日期:2015-11-01 00:00:00
abstract:OBJECTIVE:Common marmosets are considered experimental animals of primates useful for medical research. We developed several monoclonal antibodies (mAbs) directed to CD molecules to gain initial insight into the immune and hematopoietic systems of this organism, and analyzed the basic cellularity and characters of marm...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2009.08.003
更新日期:2009-11-01 00:00:00
abstract::We have reported modulation, by cytokines interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) and by hormonal cyclic-adenosine-monophosphate (cAMP) agonists, of hematopoietic growth factor production in the murine marrow adherent cell line +/+(-)1.LDA11. Previously, we reported that increased in...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1994-08-01 00:00:00
abstract::The results and complications of 224 marrow collections from 200 patients with malignant disease who underwent marrow aspiration and storage for subsequent autologous marrow transplantation (AMT) were analyzed. The median age of the patients was 35 years (range 1-68); 131 patients had hematologic malignancies and 69 h...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1985-10-01 00:00:00
abstract::Haemopoietic regeneration was studied following x-irradiation and transplantation of bone marrow from either normal or hydroxyurea-treated donor mice, to ascertain the contribution of proliferating progenitor cells to regeneration. With transplantation of equivalent numbers of CFU-S, total DNA and 3HTdR uptake into DN...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1977-09-01 00:00:00
abstract::Recently, several human bone marrow stromal cell lines have established and produced hematopoietic growth factors. One of these factors, a burst-promoting activity (BPA), was purified from 6 liters of serum-free conditioned medium cultured from stromal cell line KM-102, which was stimulated by phorbol myristate acetat...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1988-08-01 00:00:00
abstract::Blood samples were examined from 25 children with malignancies during hematopoietic recovery following chemotherapy-induced aplasia and from 9 children undergoing tonsillectomy. The proportion of CD34-positive peripheral blood mononuclear cells (PBMNC) evaluated by flow cytometry was compared with the number of coloni...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1991-12-01 00:00:00
abstract::Based on previous observations that granulocyte-macrophage colony-stimulating factor (GM-CSF) promotes granulocyte recovery following chemotherapy, we evaluated the effect of recombinant human GM-CSF on hematopoietic progenitors and clinical outcome in six patients with delayed engraftment (greater than 55 days) after...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1991-03-01 00:00:00
abstract::Septins are a family of filament-forming GTP-binding proteins that serve as scaffolds and diffusion barriers in various cellular processes. Septin 6 is known as a fusion partner of mixed-lineage leukemia in infant acute myeloid leukemia. The occurrence of the fusion gene is associated with a reduced expression of sept...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2017.07.005
更新日期:2017-11-01 00:00:00
abstract::In the accompanying paper we constructed a model for the proliferation and differentiation of granulocyte-macrophage progenitor cells in response to the specific proliferation/differentiation stimulus granulocyte-macrophage colony-stimulating activity (gm-CSA). Here we have tested the model without altering the model ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1985-02-01 00:00:00
abstract:OBJECTIVE:A multi-step statistical strategy was applied to quantify individual and interactive effects of cytokines on megakaryopoiesis and to determine the concentration of the selected cytokines that optimize ex vivo megakaryocyte (MK) expansion, maturation, and platelet production in stromal- and serum-free conditio...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2005.06.020
更新日期:2005-10-01 00:00:00
abstract:OBJECTIVE:Normal tissues, including the central nervous system, tolerate single exposures to narrow planes of synchrotron-generated x-rays (microplanar beams; microbeams) up to several hundred Gy. The repairs apparently involve the microvasculature and the glial system. We evaluate a hypothesis on the involvement of by...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2007.01.014
更新日期:2007-04-01 00:00:00
abstract::A cell line (LAMA-84) has been established from the blood of a patient with chronic myeloid leukemia in acute phase. LAMA-84 cells retained the patient's chromosome abnormalities, i.e., triplication of all chromosomes except chromosome 18, the presence of Philadelphia (Ph) chromosome in 4-5 copies, and the presence of...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1987-09-01 00:00:00
abstract::As neutropenia is a common side effect of treatment with 2-chlorodeoxyadenosine (2-CdA), we investigated the myelosuppressive action of 2-CdA in Dexter-type human long-term bone marrow cultures (LTBMCs). LTBMCs were incubated with varying doses of 2-CdA (5 to 20 nM/L) during the first week. At 20 and 10 nM/L 2-CdA, we...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1995-06-01 00:00:00