Abstract：
:Precise replacement of diseased or dysfunctional organs is the goal of regenerative medicine and has appeared to be a distant goal for a long time. In the field of hematopoietic stem cell transplantation, this goal is now becoming tangible as gene-editing technologies and novel conditioning agents are entering the clinical arena. Targeted immunologic depletion of hematopoietic stem cells (HSCs), which are at the very root of the hematopoietic system, will enable more selective and potentially more effective hematopoietic stem cell transplantation in patients with hematological diseases. In contrast to current conditioning regimes based on ionizing radiation and chemotherapy, immunologic conditioning will spare mature hematopoietic cells and cause substantially less inflammation and unspecific collateral damage to other organs. Biological agents that target the stem cell antigen CD117 are the frontrunners for this purpose and have exhibited preclinical activity in depletion of healthy HSCs. The value of anti-CD117 antibodies as conditioning agents is currently being evaluated in early clinical trials. Whereas mild, antibody-based immunologic conditioning concepts might be appropriate for benign hematological conditions in which incomplete replacement of diseased cells is sufficient, higher efficacy will be required for treatment and elimination of hematologic stem cell malignancies such as acute myeloid leukemia and myelodysplastic syndrome. Antibody-drug conjugates, bispecific T-cell engaging and activating antibodies (TEAs), or chimeric antigen receptor (CAR) T cells might offer increased efficacy compared with naked antibodies and yet higher tolerability and safety compared with current genotoxic conditioning approaches. Here, we summarize the current state regarding immunologic conditioning concepts for the treatment of HSC disorders and outline potential future developments.
journal_name
Exp Hematoljournal_title
Experimental hematologyauthors
Russkamp NF,Myburgh R,Kiefer JD,Neri D,Manz MGdoi
10.1016/j.exphem.2021.01.003subject
Has Abstractpub_date
2021-01-20 00:00:00eissn
0301-472Xissn
1873-2399pii
S0301-472X(21)00004-7pub_type
杂志文章abstract：OBJECTIVE:Beta-thalassemia results from beta-globin gene mutations that lead to ineffective erythropoiesis, shortened red cell survival, and anemia. Patients with beta-thalassemia develop iron overload, despite which, hepcidin levels are low. This suggests that hepcidin regulation in beta-thalassemia is more sensitive ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2008.10.004
更新日期：2009-02-01 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：: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：:The presence of multilineage dysplasia (MLD) by morphology at diagnosis in acute myeloid leukemia (AML) defines a separate subset in the World Health Organization classification with still-debated prognostic value. A major controversy concerns MLD's role in NPM1-mutated (NPM1⁺) AML, which correlates with good prognosi...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2015.06.003
更新日期：2015-10-01 00:00:00
abstract：:The effect on marrow myeloblast colony formation in blood from nine patients with acute myeloid leukemia was studied by using three recombinant-DNA-derived human leukocyte interferons (IFN alpha 2, IFN alpha-A, and IFN alpha-C). In preliminary experiments, a brief exposure of leukemic marrow cells to IFN alpha resulte...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1985-10-01 00:00:00
abstract：OBJECTIVES:To identify the regulatory sequences driving Gata1 expression in conventional dendritic cells (cDC). MATERIALS AND METHODS:The number and expression levels of Gata1, Gata1-target genes and hypersensitive site (HS) 2 (the eosinophil-specific enhancer)-driven green fluorescent protein (GFP) reporter of cDCs f...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2010.03.006
更新日期：2010-06-01 00:00:00
abstract：:Regeneration of the bone marrow microenvironment after transplantation of allogeneic hematopoietic stem cells is poorly explored. The goal of our study was to investigate this process focusing on immunologic factors: concentrations of selected cytokines, expression of immunosuppressive proteins CD47 and CD274 on hemat...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2016.08.001
更新日期：2016-12-01 00:00:00
abstract：:Histone deacetylase inhibitors (HDACIs) have demonstrated effectiveness against lymphomas and myelomas in clinical practice. However, common to all currently approved broad-acting HDACIs (panHDACIs) is dose-limiting thrombocytopenia, which has prevented wider use in cancer therapy. Using CD34+ hematopoietic stem cells...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2018.12.007
更新日期：2019-04-01 00:00:00
abstract：:In slightly more than a decade of stem cell plasticity research, 24 peer-reviewed articles have demonstrated plasticity across organ and/or embryonic lineage boundaries at the single-cell level, with only 1 article showing negative results. These data, taken together with data about reversibility of gene restrictions ...
journal_title：Experimental hematology
pub_type： 杂志文章,评审
doi：10.1016/j.exphem.2010.04.013
更新日期：2010-07-01 00:00:00
abstract：:Addition of serum or plasma from many species increased the number and size of neutrophilic granulocyte and macrophage colonies formed in vitro by mouse bone marrow cells after stimulation by a variety of preparations containing colony stimulating factor (CSF). The active factor in serum was heat-labile, non-dialyzabl...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1975-08-01 00:00:00
abstract：OBJECTIVE:Resveratrol (3,4',5,-trihydroxystilbene, RV), an ingredient of wine, is an inhibitor of the proliferation-linked enzyme ribonucleotide reductase (RR) and shows a broad spectrum of cytotoxic effects against human cancer cells. In order to enhance these effects, we introduced additional hydroxyl moieties into t...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2006.05.018
更新日期：2006-10-01 00:00:00
abstract：UNLABELLED:In this paper we describe an experimental model for ex vivo purging of contaminating tumor cells from peripheral blood stem cell (PBSC) collections obtained from patients with acute myeloblastic leukemia (AML). We studied the combination of the alkylating agent nitrogen mustard (NM; concentrations ranging fr...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1997-11-01 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：OBJECTIVE:To investigate the role of perforin-mediated cell apoptosis in murine models of immune-mediated bone marrow (BM) failure. MATERIALS AND METHODS:We compared C57BL/6J (B6) mice carrying a perforin gene deletion (Prf(-/-)) with wild-type (WT) controls for cellular composition in lymphohematopoietic tissues. Lym...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2008.12.001
更新日期：2009-04-01 00:00:00
abstract：OBJECTIVE:Several transducing molecules, including JAK2, STAT5, MAP kinases, phosphatidylinositol 3-kinase (PI3K), phospholipase C-gamma1, and PKC are activated by interaction between erythropoietin (EPO) and the EPO receptor. The aim of this was to examine the relative involvement of PI3K in the development of glycoph...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(02)00868-8
更新日期：2002-09-01 00:00:00
abstract：:In vitro studies of human hemopoiesis are often limited by the availability of normal bone marrow. We have overcome this difficulty by taking advantage of the bone marrow fragments removed during total hip replacement. We report here a comparative study of the colony forming capacity of trochanter and sternal or iliac...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1979-07-01 00:00:00
abstract：:Many granulocyte-specific mouse monoclonal antibodies recognize the carbohydrate sequence 3-fucosyllactosamine, Ga 1 beta 1-4[Fuc alpha 1-3]GlcNAc, which occurs in cell-surface glycolipids and glycoproteins. In general, these antibodies bind to blast cells from most patients with acute myeloblastic leukemia, but not t...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1986-08-01 00:00:00
abstract：OBJECTIVE:High-dose radiation exposure induces acute myeloid leukemia (AML) in C3H mice, most of which have a frequent hemizygous deletion around the D2Mit15 marker on chromosome 2. This region includes PU.1, a critical candidate gene for initiation of leukemogenesis. To identify novel cooperative genes with PU.1, rele...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2008.01.015
更新日期：2008-07-01 00:00:00
abstract：:Epitopes on the CD34 molecule detected by some CD34 antibodies can be cleaved by a unique glycoprotease from Pasteurella haemolytica, which cleaves only glycoproteins rich in O-linked glycans. A method to isolate CD34+ cells from adult bone marrow was developed subsequently, in which CD34+ cells were isolated in high ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1996-06-01 00:00:00
abstract：OBJECTIVE:Clonal stem cell proliferation and increased erythrocyte mass are hallmarks of the myeloproliferative disorder polycythemia vera (PV). The molecular basis of PV is unknown. METHODS:We carried out a genome-wide screening for loss of heterozygosity (LOH) and analyzed candidate genes within the LOH loci. RESUL...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(01)00789-5
更新日期：2002-03-01 00:00:00
abstract：:Details are given of response and toxicity after high dose chemotherapy followed by autologous bone marrow infusion. High dose nitrosurea therapy (600-1000 mg/m2 BCNU) was predominantly associated with hematopoietic toxicity but recovery was within 4-5 weeks after BCNU therapy. High dose combination chemotherapy using...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1979-01-01 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：:More than 2million human erythroblasts extrude their nuclei every second in bone marrow under hypoxic conditions (<7% O2). Enucleation requires specific signal transduction pathways and the local assembly of contractile actomyosin rings. However, the energy source driving these events has not yet been identified. We e...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2019.02.004
更新日期：2019-04-01 00:00:00
abstract：:Serum albumin has long been an essential supplement for ex vivo hematopoietic and immune cell cultures. However, serum albumin medium supplements represent a major source of biological contamination in cell cultures and often cause loss of cellular function. As serum albumin exhibits significant batch-to-batch variabi...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2019.11.007
更新日期：2019-12-01 00:00:00
abstract：:Serum obtained from (C3H X C57BL) F1 hybrid mice injected with parental (C57BL) lymph node cells after 600 rad irradiation contained a high level of an erythropoietic factor, which enhanced erythroid colony formation by fetal C57BL liver cells in methylcellulose cultures. The serum level of this erythroid colony-stimu...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1984-11-01 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：:Radiation damage to femoral hemopoietic stroma in mice was measured 6 weeks after irradiation and reconstitution with syngeneic bone marrow by quantitation of fibroblastic progenitor cells (CFUF), and by assaying hemopoietic progenitors and CFUF numbers in regenerated subcutaneous femur implants. A dose-dependent effe...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1983-10-01 00:00:00
abstract：OBJECTIVE:We studied two adult brothers with severe congenital thrombocytopenia in order to determine the genetic etiology of their inherited disorder. Despite the absence of eczema or immunodeficiency, a mutation of the Wiskott-Aldrich syndrome (WAS) gene was suspected because of the presence of microthrombocytes. MA...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(02)01023-8
更新日期：2003-02-01 00:00:00
abstract：:Previously, recombinant erythropoietin (rEpo) was shown to increase the number and size of megakaryocytic colonies in vitro, and in vivo it elevates the number of megakaryocytes in mouse spleens. To test the hypothesis that rEpo would stimulate platelet production in mice, both normal mice and mice in rebound-thromboc...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1987-07-01 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
