Abstract:
:Graft-versus-host disease (GVHD), mediated by donor-derived alloreactive T cells, is a major cause of nonrelapse mortality in allogeneic hematopoietic stem cell transplantation. Its therapy is not well-defined. We established allele-specific anti-human leukocyte antigen (HLA) monoclonal antibodies (ASHmAbs) that specifically target HLA molecules, with steady death of target-expressing cells. One such ASHmAb, against HLA-A*02:01 (A2-kASHmAb), was examined in a xenogeneic GVHD mouse model. To induce fatal GVHD, non-irradiated NOD/Shi-scid/IL-2Rγ(null) mice were injected with healthy donor human peripheral blood mononuclear cells, some expressing HLA-A*02:01, some not. Administration of A2-kASHmAb promoted the survival of mice injected with HLA-A*02:01-expressing peripheral blood mononuclear cells (p < 0.0001) and, in humanized NOD/Shi-scid/IL-2Rγ(null) mice, immediately cleared HLA-A*02:01-expressing human blood cells from mouse peripheral blood. Human peripheral blood mononuclear cells were again detectable in mouse blood 2 to 4 weeks after A2-kASHmAb administration, suggesting that kASHmAb may be safely administered to GVHD patients without permanently ablating the graft. This approach, different from those in existing GVHD pharmacotherapy, may open a new door for treatment of GVHD in HLA-mismatched allogeneic hematopoietic stem cell transplantation.
journal_name
Exp Hematoljournal_title
Experimental hematologyauthors
Nakauchi Y,Yamazaki S,Napier SC,Usui J,Ota Y,Takahashi S,Watanabe N,Nakauchi Hdoi
10.1016/j.exphem.2014.10.008subject
Has Abstractpub_date
2015-02-01 00:00:00pages
79-88.e1-4issue
2eissn
0301-472Xissn
1873-2399pii
S0301-472X(14)00714-0journal_volume
43pub_type
杂志文章abstract:OBJECTIVE:Recent clinical trials of adoptive immunotherapy showed diminished reactivity of human T cells upon ex vivo manipulation. For a safe and effective clinical application of human T cells, it is necessary to improve ex vivo manipulation procedures and evaluate their impact on in vivo functionality. However, ther...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2006.09.018
更新日期:2007-01-01 00:00:00
abstract::Initiation of DNA synthesis by recombinant colony-stimulating factors (CSFs) was assessed in normal human marrow blast cells isolated by expression of CD34 antigen (tritiated thymidine incorporation). Continuous exposure to CSF was required. A mild increase in DNA synthesis was initiated by granulocyte CSF (G-CSF; gre...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1991-09-01 00:00:00
abstract::Arsenic trioxide (As2O3) has been demonstrated to be effective for the treatment of acute promyelocytic leukemia (APL) and to inhibit proliferation and produce apoptosis in the APL cell line NB4. To determine if As2O3 might be useful for the treatment of other lineages, we investigated the effects of As2O3 on viabilit...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(99)00014-4
更新日期:1999-05-01 00:00:00
abstract::Drug resistance remains a serious problem in leukemia therapy. Among newly developed nucleoside antimetabolites, clofarabine has broad cytotoxic activity showing therapeutic promise and is currently approved for relapsed acute lymphoblastic leukemia. To investigate the mechanisms responsible for clofarabine resistance...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2014.11.001
更新日期:2015-03-01 00:00:00
abstract::The synthesis and expression of protein complexes of 23,000 and 30,00 dalton (p23,30) HLA-DR antigen, and of 44,000 and 12,000 dalton (p44,12) HLA-A,B antigen and beta 2-microglobulin was demonstrated on human peripheral blood monocytes and in cultures of purified, adherent monocytes. In indirect immunofluorescence as...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1980-07-01 00:00:00
abstract::In adult hematopoiesis, the hematopoietic stem cell (HSC) sits at the top of a hierarchy of hematopoietic progenitors responsible for generating the diverse repertoire of blood and immune cells. During embryonic development, however, the initial waves of hematopoiesis provide the first functioning blood cells of the d...
journal_title:Experimental hematology
pub_type: 杂志文章,评审
doi:10.1016/j.exphem.2017.12.008
更新日期:2018-04-01 00:00:00
abstract:OBJECTIVE:The aim of this study was to develop novel markers for enrichment of hematopoietic progenitors from bone marrow of swine. MATERIALS AND METHODS:We previously showed that pig bone marrow contains a "side population" (SP) of Hoechst dye-effluxing cells that resembles the hematopoietic stem cell (HSC)-containin...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(02)00835-4
更新日期:2002-07-01 00:00:00
abstract::The effects of a single injection of hemin on murine marrow BFU-E and CFU-S were assessed to determine whether hemin is as effective in augmenting primitive (day 7) BFU-E levels in situ as it is in vitro and to assess hemin's action on transplantable pluripotent stem cells (CFU-S). The results show that hemin exerts a...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1984-11-01 00:00:00
abstract::A transplanted tumor that induces granulocytosis and produces colony stimulating factor (CSF) was studied in mice during several passages. The sequence of events leading to granulocytosis was characterized. Band granulocytes were increased 3 days after tumor inoculation, while simultaneously CFU-s and CFU-c in bone ma...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1978-04-01 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::Megakaryocytic differentiation of progenitor cells was investigated in nine patients with low-risk myelodysplastic syndromes (MDS) (eight refractor anemia [RA] and one RA with ringed sideroblasts [RARS] and five patients with high-risk MDS (two RA with excess of blasts [RAEB] and three RAEB in transformation [RAEB-T])...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(98)00077-0
更新日期:1999-03-01 00:00:00
abstract:OBJECTIVE:The CD15 (Lewis x) cell surface oligosaccharide moiety is expressed in a variety of normal and tumor cells and recognized by selectins. The detection of CD15 on malignant Hodgkin-Reed-Sternberg (HRS) cells serves as a diagnostic marker of Hodgkin's lymphoma (HL). Retrospective studies suggest that the express...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(03)00237-6
更新日期:2003-11-01 00:00:00
abstract:OBJECTIVE:We have previously shown that nitric oxide (NO) is involved in the hydroxyurea-induced increase of gamma-globin gene expression in cultured human erythroid progenitor cells and that hydroxyurea increases NO production in endothelial cells via endothelial NO synthase (NOS). We have now expanded those studies t...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2009.06.009
更新日期:2009-10-01 00:00:00
abstract::Cell proliferation was investigated in normal and Rauscher Leukemia Virus-infected BALB/c mice. Five days after inoculation, islands of leukemic blasts arose in the red pulp, and proliferated as shown by autoradiographic analysis after a pulse of 3H-Thymidine. These cells subsequently infiltrated the whole spleen and ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1978-06-01 00:00:00
abstract::Hepcidin is the key regulator of iron absorption and recycling, and its expression is suppressed by red blood cell production. When erythropoiesis is expanded, hepcidin expression decreases. To gain insight into the stage of erythroid differentiation at which the regulation might originate, we measured serum hepcidin ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2015.03.001
更新日期:2015-06-01 00:00:00
abstract:OBJECTIVE:The aim of this study was to evaluate the occurrence of T-cell spontaneous apoptosis (A(spont)) and its modulation in vitro by the interleukin-2 receptor (IL-2R) gamma-chain (gammac)-signaling cytokine IL-15 in patients transplanted with autologous peripheral blood progenitor cells (PBPC) for hematologic mali...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(01)00747-0
更新日期:2001-12-01 00:00:00
abstract::We have studied the effect of cortisone acetate (CA) on two important biological functions: (1) on NK cell-mediated cytotoxicity of B6D2F1 mice to T cell lymphoma, YAC-1 and (2) on hybrid resistance of mice to parental B6 bone marrow grafts. Results of our experiments have shown that 5 mg of CA administered i.p. was e...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1981-08-01 00:00:00
abstract:OBJECTIVE:To identify genes involved in megakaryopoiesis, high-density oligonucleotide microarrays were used to compare transcript profiles from undifferentiated CD34+CD38lo cells and culture-derived megakaryocytes (MKs). MATERIALS AND METHODS:Megakaryocyte differentiation was achieved in vitro by inducing primary hum...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2004.04.002
更新日期:2004-07-01 00:00:00
abstract:OBJECTIVE:The tumor suppressor p15Ink4b (Ink4b) is a cell-cycle inhibitor that is inactivated in a high percentage of acute myeloid leukemia and myeloid dysplasia syndrome cases. Despite this, the role of Ink4b in hematopoiesis remains unclear. Here we examined the role of Ink4b in blood cell formation using Ink4b-defi...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2006.11.005
更新日期:2007-03-01 00:00:00
abstract::Classical studies of the developing embryo first suggested the existence of the hemangioblast, a precursor cell with the potential to differentiate into both blood and blood vessels. Several lines of investigation demonstrated that many of the genes activated during early hematopoietic development are also expressed i...
journal_title:Experimental hematology
pub_type: 杂志文章,评审
doi:10.1016/j.exphem.2003.07.001
更新日期:2003-11-01 00:00:00
abstract::Cells of two transplantable leukemias of mice, one myeloid and one lymphoid, were labeled with 51Cr in order to follow their distribution in hemopoietic and parenchymatous organs and blood of syngeneic recipients. Distribution of myeloid leukemia cells was compared with that of regenerating bone marrow cells and norma...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1978-01-01 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::Persistent reductions in the femoral content of hemopoietic colony-forming cells (CFU-S and GM-CFC) were observed after four doses of irradiation, delivered with three weeks between doses. In general, the reductions were dose dependent, and similar reductions were produced by single doses and repeated doses using the ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1986-03-01 00:00:00
abstract::Marrow from Sl/Sld mice (in which the hemopoietic stromal microenvironment is defective), when implanted beneath the renal capsule of a normal littermate, produces an ectopic marrow site containing the same number of stem cells (CFU-S) and nearly as many GM-CFC as that obtained by implanting marrow from a normal litte...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1987-03-01 00:00:00
abstract::The four existing animal models of cyclic hematopoiesis are briefly described. The unusual erythropoietin (Ep) responses of the W/Wv mouse, the Sl/Sld mouse, and cyclic hematopoietic dog are reviewed. The facts reviewed indicate that the bone marrow itself is capable of influencing regulatory events of hematopoiesis. ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1983-08-01 00:00:00
abstract::The survival rate and recovery of peripheral blood cells and platelets were studied in Balb/c mice subjected to different single doses of whole-body irradiation and treated with a combination of interleukin-3 (IL-3) and interleukin-11 (IL-11). In a first group of 20 mice, 7.5 Gy irradiation, immediately followed by 2 ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1996-09-01 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::Hematopoietic stem cells (HSC) rely on a highly regulated molecular network to balance self-renewal and lineage specification to sustain life-long hematopoiesis. Despite a plethora of studies aimed at identifying molecules governing HSC fate, our current knowledge of the genes responsible is limited. We have found ins...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2016.01.010
更新日期:2016-05-01 00:00:00
abstract::Germinal center-associated nuclear protein (GANP) is a unique and multifunctional protein that plays a critical role in cell biology, neurodegenerative disorders, immunohematology, and oncogenesis. GANP is an orthologue of Saccharomyces Sac3, one of the components of the transcription export 2 (TREX-2) complex and a m...
journal_title:Experimental hematology
pub_type: 杂志文章,评审
doi:10.1016/j.exphem.2020.08.007
更新日期:2020-10-01 00:00:00
abstract::In a nonrandomized study, hematopoietic recovery kinetics were evaluated in 98 consecutive patients who underwent high-dose chemotherapy without total body irradiation (TBI) and autologous peripheral blood stem cell transplantation (PBSCT). Fifty-three patients received recombinant human granulocyte colony-stimulating...
journal_title:Experimental hematology
pub_type: 临床试验,杂志文章
doi:
更新日期:1994-11-01 00:00:00