Abstract:
OBJECTIVES:We previously demonstrated that allogeneic bone marrow transplantation (BMT) after low-dose total lymphoid irradiation (200 cGy) and depletion of donor-reactive cells with cyclophosphamide (Cy) converted recipients to graft-vs-host disease (GVHD)-free chimeras tolerant to donor skin grafts. BMT also generated strong graft-vs-leukemia (GVL) response. However, clinical application of the protocol was hampered by the requirement for a relatively high dose of Cy (200 mg/kg). In this study we have tried to minimize the Cy dose by a concomitant blockade of CD40-CD40L interaction. MATERIALS AND METHODS:Mildly irradiated BALB/c mice were primed with C57BL/6 BM cells (BM(1)) and skin graft on day 0, injected with Cy (200 mg/kg or less) on day 1, and transplanted with a second C57BL/6 BM cell inoculum (BM(2)) on day 2. CD40L-specific antibody (MR1) was given with BM(1), BM(2), and 2 days later. Treated animals were monitored for survival, chimerism, and skin allograft rejection. The GVL potential of transplanted cells was examined in mice inoculated with BCL1 leukemia cells before irradiation. RESULTS:Blocking CD40-CD40L interaction with MR1 mAb allowed the reduction of a tolerance-generating Cy dose by 50%. Unfortunately, adding MR1 to the protocol reduced the GVL potential of the transplanted cells. Neither low-dose Cy nor antibodies alone could downregulate donor or recipient immune response. CONCLUSIONS:CD40L-specific antibodies synergize with Cy to induce bilateral transplantation tolerance. Therefore, their use may be beneficial for safer allogeneic BMT for nonmalignant indications. However, due to MR1-associated reduction of GVL effects, MR1 should be considered with caution as conditioning for BMT for leukemia-bearing recipients.
journal_name
Exp Hematoljournal_title
Experimental hematologyauthors
Prigozhina TB,Gurevitch O,Elkin G,Morecki S,Yakovlev E,Slavin Sdoi
10.1016/s0301-472x(02)01009-3keywords:
subject
Has Abstractpub_date
2003-01-01 00:00:00pages
81-8issue
1eissn
0301-472Xissn
1873-2399pii
S0301472X02010093journal_volume
31pub_type
杂志文章abstract::Our previous studies have shown that a unique glycoprotease from Pasteurella haemolytica specifically cleaves only proteins containing sialylated O-linked glycans. The hematopoietic progenitor cell antigen, CD34, which is heavily glycosylated with both N- and O-linked glycans, is readily cleaved by this protease. In t...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1992-06-01 00:00:00
abstract::The processing of inflammatory signals occurs through a variety of mechanisms; the recent descriptions of the tethered ligand receptor for thrombin (JA Hoxie et al., J Biol Chem 268:13756, and TK Vu et al., Cell 64:1057) provide a novel route and mechanism for cellular activation after inflammation and thrombosis. Usi...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1996-07-01 00:00:00
abstract:OBJECTIVE:Mobilized peripheral blood (PB) progenitors are increasingly used in autologous and allogeneic transplantation. However, the short- and long-term engraftment potential of mobilized PB or bone marrow (BM) has not been directly compared. Although several studies showed that BM-derived Lin(-)CD34(-) cells contai...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(00)00506-3
更新日期:2000-09-01 00:00:00
abstract:OBJECTIVE:In utero hematopoietic cell transplantation (IUHCT) is a non-ablative approach that achieves mixed allogeneic chimerism and donor-specific tolerance. However, clinical application of IUHCT has been limited by minimal engraftment. We have previously demonstrated in the murine model that low-level allogeneic ch...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2005.11.011
更新日期:2006-03-01 00:00:00
abstract::Induced pluripotent stem cells (iPSCs) can be generated from various types of cells with transduction of defined transcription factors. Patient-derived iPSCs are becoming commonly utilized for understanding the molecular pathways involved in disease and for the development of novel targeted therapies. With the use of ...
journal_title:Experimental hematology
pub_type: 杂志文章,评审
doi:10.1016/j.exphem.2015.06.006
更新日期:2015-08-01 00:00:00
abstract::Peripheral blood progenitor cells (PBPC) mobilized by granulocyte colony-stimulating factor (G-CSF) promptly engraft allogeneic recipients after myeloablative chemotherapy for hematologic malignancies. Surprisingly, no exacerbation of acute graft-vs-host disease has been observed despite a 10-fold higher T-cell conten...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(01)00617-8
更新日期:2001-04-01 00:00:00
abstract::More than 90% of patients with severe congenital neutropenia (SCN) respond to granulocyte colony-stimulating factor (G-CSF) therapy. The basis for the refractory state in the remaining patients is unknown. To address this issue, we studied a child with SCN who was totally unresponsive to G-CSF and had a novel point mu...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(00)00544-0
更新日期:2000-12-01 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::Addition of carbamylcholine, a cholinergic analogue, to bone marrow cultures enhanced megakaryocytic and granulocytic growth by 60% and 42%, respectively. When carbamylcholine was added to spleen cells cultured in the presence of pokeweed mitogen, the resulting conditioned medium (PWM-SCM) increased the number of mega...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1989-12-01 00:00:00
abstract::Haploinsufficiency of erythroid Krüppel-like factor (EKLF/KLF1) has been shown recently to ameliorate the clinical severity of β-thalassemia by increased expression levels of fetal hemoglobin (HbF). The underlying mechanisms for role of EKLF in regulating HbF are of great interest but remain incompletely understood. I...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2018.03.004
更新日期:2018-07-01 00:00:00
abstract:OBJECTIVE:Cyclosporine A (CsA), known as an effective immunosuppressive agent, is widely used in clinical fields. Mesenchymal stem cells may exert immunomodulatory effects on the immune system, but the exact mechanisms underlying them remain controversial. Here we investigated whether human adipose tissue-derived mesen...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2010.10.009
更新日期:2011-02-01 00:00:00
abstract::Peritoneal injection of thioglycollate medium (TM) to mice results in a dramatic increase in total number of peritoneal macrophages within 48 to 72 hours. Unlike resident macrophages, a fraction (10 to 20%) of these newly arrived young macrophages, designated as macrophage colony-forming cells (M-CFC), are highly prol...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1993-11-01 00:00:00
abstract:OBJECTIVE:The aim of this study was to develop an animal model for human acute lymphoblastic leukemia (ALL) in which the kinetics and characteristics of leukemia can be sequentially monitored in individual mice. MATERIALS AND METHODS:NOD/SCID mice were inoculated intravenously with primary ALL. Progression of leukemia...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(00)00669-x
更新日期:2001-03-01 00:00:00
abstract::Induction of fetal hemoglobin (HbF) is considered a promising strategy in the treatment of β-thalassemia, in which production of adult hemoglobin (HbA) is impaired by mutations affecting the β-globin gene. Recent results indicate that B-cell lymphoma/leukemia 11A (BCL11A) is a major repressor of γ-globin gene expressi...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2015.08.011
更新日期:2015-12-01 00:00:00
abstract:OBJECTIVE:The aim of this study was to evaluate the effect of CF101, a synthetic agonist to the A3 adenosine receptor (A3AR), on the production of granulocyte colony-stimulating factor (G-CSF). The ability of CF101 to act as a myeloprotective agent in chemotherapy-treated mice was tested. METHODS:CF101 was administere...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(02)00962-1
更新日期:2002-12-01 00:00:00
abstract::Exit of primitive hematopoietic progenitor cells (HPCs) from the G0 phase of the cell cycle in response to in vitro cytokine stimulation is a limiting step in successful ex vivo expansion. Simultaneous DNA/RNA staining with Hoechst 33342 and pyronin Y was used to separate human bone marrow CD34+ cells residing in G0 (...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1998-07-01 00:00:00
abstract:OBJECTIVE:Thrombopoietin stimulates megakaryopoiesis and platelet production by binding to its receptor, Mpl, on hematopoietic progenitor cells. Previously, a murine VB22B minibody for Mpl was shown to stimulate megakaryocyte colony formation in vitro and increase the platelet count in cynomolgus monkeys. In this study...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2011.05.001
更新日期:2011-08-01 00:00:00
abstract::Patients subjected to prolonged exposure to nitrous oxide (N2O) often develop megaloblastic bone marrow changes. This toxicity is due to the N2O-mediated inactivation of cobalamin-dependent enzymes with resultant perturbations in cell metabolism. The effect of N2O on the behavior of murine colony-forming units-cytokin...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1993-02-01 00:00:00
abstract::Leukemic monoblasts obtained from three children were evaluated for their in vitro physiologic characteristics. These monoblasts were alpha naphthyl acetate esterase positive, exhibited glass adherence, had IgG membrane receptors, phagocytized latex particles with subsequent nitroblue tetrazolium (NBT) reduction, and ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1978-01-01 00:00:00
abstract::Circulating CD14(+) monocytes are originated from hematopoietic stem cells in the bone marrow and believed to be committed precursors for phagocytes, such as macrophages. Recently, we have reported a primitive cell population termed monocyte-derived multipotential cells (MOMCs), which has a fibroblast-like morphology ...
journal_title:Experimental hematology
pub_type: 杂志文章,评审
doi:10.1016/j.exphem.2010.03.015
更新日期:2010-07-01 00:00:00
abstract::Heterozygous alpha-thalassemic (Hbath/+) female mice were investigated for the effect of persistent erythropoietic stress on the number of stem cells and progenitor cells along the the erythroid (E), granulocyte-macrophage (GM), and megakaryocyte (Meg) pathways. At the progenitor cell level, compensatory erythropoiesi...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1986-05-01 00:00:00
abstract:OBJECTIVE:Myeloid ectropic viral integration site 1 (MEIS1) is a Hox cofactor known for its role in development and is strongly linked to normal and leukemic hematopoiesis. Although previous studies have focused on identifying protein partners of MEIS1 and its transcriptionally regulated targets, little is known about ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2010.06.006
更新日期:2010-09-01 00:00:00
abstract:OBJECTIVE:T lymphocytes can be activated by soluble factors such as cytokines or through direct cell-cell interactions. Although cytokine receptors are known to signal through STAT family transcription factors, the mechanisms by which other cell-surface molecules, such as CD2, transduce signals is unclear. The goal of ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(00)00652-4
更新日期:2001-02-01 00:00:00
abstract::Colony forming unit (CFU) assays were developed for feline granulocyte-macrophage (CFUGM), early erythroid (day 2 CFUE), and late erythroid (day 7 CFUE) colonies in methylcellulose medium. Feline CFUGM and both day 2 and day 7 CFUE were enhanced by feline macrophage conditioned medium and late CFUE often were intimate...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1981-11-01 00:00:00
abstract::We have recently shown that interleukin 6 (IL-6) induces transient expression of the alpha-chain of the interleukin 2 receptor (IL-2R alpha) in the murine leukemia myeloid M1 cell line. Others have reported that IL-6 and interleukin 1 (IL-1) synergistically enhance the expression of IL-2R alpha in T cells. Thus, in th...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1992-11-01 00:00:00
abstract::Media conditioned by B-lymphocytes of patients with chronic lymphocytic leukemia (B-CLL) induced the formation of multilineage colonies (CFU-GEMM) in cultures of human target marrow cells. Maximum levels of stem cell colony-stimulating activity (CFU-GEMMCSA) were detected by day 3 of leukemic B-cell cultures, remainin...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1987-02-01 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::The expression of exogenous genes in long-lived primary T cells is potentially beneficial for the treatment of various diseases including cancer, AIDS, genetic defects of the lymphoid compartment, and systemic enzyme deficiencies such as hemophilia. One approach for genetic modification of T cells is to introduce ther...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1996-10-01 00:00:00
abstract::Delayed platelet recovery and altered marrow megakaryocytopoiesis was observed in highly irradiated mice following transplantation with 1000 lineage-negative, stem cell antigen-positive (Lin-Sca-1+) cells. Thirty days after transplantation, the mice were thrombocytopenic. Normal platelet levels were reestablished by 9...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1993-12-01 00:00:00
abstract:BACKGROUND:Autologous bone marrow transplantation is an important therapy for patients with acute myelogenous leukemia (AML). However, leukemia in the graft may contribute to posttransplant relapse. Treatment of the graft with 4-hydroperoxycyclophosphamide (4HC) is sometimes used to decrease numbers of infused leukemia...
journal_title:Experimental hematology
pub_type: 杂志文章,多中心研究
doi:10.1016/s0301-472x(01)00732-9
更新日期:2001-11-01 00:00:00