Abstract:
:The history of clonal hematopoiesis (CH) research is punctuated by several seminal discoveries that have forged our understanding of cancer development. The clever application of the principle of random X-chromosome inactivation (XCI) in females led to the development of the first test to identify clonal derivation of cells. Initially limited by a low level of informativeness, the applicability of these assays expanded with differential methylation-based assays at highly polymorphic genes such as the human androgen receptor (HUMARA). Twenty years ago, the observation that skewing of XCI ratios increases as women age was the first clue that led to the identification of mutations in the TET2 gene in hematologically normal aging individuals. In 2014, large-scale genomic approaches of three cohorts allowed definition of CH, which was reported to increase the risk of developing hematologic cancers and cardiovascular diseases. These observations created a fertile field of investigation aimed at investigating the etiology and consequences of CH. The most frequently mutated genes in CH are DNMT3A, TET2, and ASXL1, which have a role in hematopoietic stem cell (HSC) development and self-renewal. These mutations confer a competitive advantage to the CH clones. However, the penetrance of CH is age dependent but incomplete, suggesting the influence of extrinsic factors. Recent data attribute a modest role to genetic predisposition, but several observations point to the impact of a pro-inflammatory milieu that advantages the mutated clones. CH may be a barometer of nonhealthy aging, and interventions devised at curbing its initiation or progression should be a research priority.
journal_name
Exp Hematoljournal_title
Experimental hematologyauthors
Ayachi S,Buscarlet M,Busque Ldoi
10.1016/j.exphem.2020.01.008subject
Has Abstractpub_date
2020-03-01 00:00:00pages
2-11eissn
0301-472Xissn
1873-2399pii
S0301-472X(20)30029-1journal_volume
83pub_type
历史文章,杂志文章,评审abstract:OBJECTIVE:Podocalyxin expression on Ter119(+) erythroblasts is induced following administration of erythropoietin (Epo) or phenylhydrazine treatment, but is notably absent on committed erythroid progenitors during homeostatic red cell turnover. Following high-dose Epo administration in vivo, podocalyxin surface express...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2008.09.006
更新日期:2009-01-01 00:00:00
abstract::The development of pluripotential hematopoietic stem cells (PHSC) requires the continuous support provided by the bone tissue and bone marrow (BM) stromal cells. The basic rule of spatial and temporal organization of the distinct stromal cells and differentiating hematopoietic cells in the course of development, regen...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1995-04-01 00:00:00
abstract::Embryonic and adult stem cell populations have great potential value in medicine, and hematopoietic stem cells are already being used in transplantation. Definition of these populations to increase our understanding of the programs that control differentiation, self-renewal, and possibly plasticity would be of great i...
journal_title:Experimental hematology
pub_type: 杂志文章,评审
doi:10.1016/j.exphem.2003.08.012
更新日期:2003-12-01 00:00:00
abstract::Myelodysplastic syndromes (MDS) are clonal stem cell diseases of the bone marrow characterized by abnormalities in maturation of hematopoietic cells of all lineages. MDS patients frequently have lower lipids and high rates of apoptosis and p53 (TP53) expression. An association between the reduced lipids in MDS and the...
journal_title:Experimental hematology
pub_type: 临床试验,杂志文章
doi:10.1016/j.exphem.2012.02.003
更新日期:2012-07-01 00:00:00
abstract:OBJECTIVES:Processing of epigenomic transcriptional information by cell cycle phase G(1) and decision-making at checkpoint G(1)/S are the final organizational steps preceding gene replication in transcriptional reorientation programs (i.e., switches from proliferation to cycle arrest and neoplastic transformation). Fur...
journal_title:Experimental hematology
pub_type: 杂志文章,评审
doi:10.1016/j.exphem.2008.07.009
更新日期:2008-11-01 00:00:00
abstract::Disruption of ribosomal proteins is associated with hematopoietic phenotypes in cell culture and animal models. Mutations in ribosomal proteins are seen in patients with Diamond Blackfan anemia, a rare congenital disease characterized by red cell aplasia and distinctive craniofacial anomalies. A zebrafish screen uncov...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2011.11.007
更新日期:2012-03-01 00:00:00
abstract::Previous studies have suggested that in vivo granulocyte colony-stimulating factor (G-CSF) pharmacokinetics may change over time. We studied three patients treated with high-dose chemotherapy followed by autologous bone marrow transplantation (ABMT) for metastatic breast cancer after intravenous administration of reco...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1997-12-01 00:00:00
abstract:OBJECTIVE:Several compounds, including butyrate and trichostatin A, have been shown to activate gamma-gene expression via p38 mitogen-activated protein kinase (MAPK) signaling. In eukaryotic cells, reactive oxygen species (ROS) act as signaling molecules to mediate phosphorylation of tyrosine kinases such as p38 MAPK t...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2005.12.009
更新日期:2006-03-01 00:00:00
abstract::The human cell line CMK spontaneously expresses megakaryocytic characteristics and can be induced to differentiate into mature megakaryocytes after exposure to 12-O-tetradecanoylphorbol-13-acetate (TPA). In comparison with CMK, we have examined the characteristics of a subclone, designated as CMK11-5, that is morpholo...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1991-10-01 00:00:00
abstract:OBJECTIVE:Bone marrow contains a subset of stem cells that give rise to nonhematopoietic lineages. These nonhematopoietic stem cells appear heterogeneous and contain cells committed to mesenchymal and endothelial lineages, as well as more primitive multipotential cells resembling progenitors of germ cells and very smal...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2009.05.014
更新日期:2009-09-01 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::To clarify the effects of androgen on hemopoiesis in mice, we investigated changes in hemopoietic stem cells at various stages of differentiation after injection of 19-nandrolone decanoate (19-ND). 19-ND induced (a) a marked increase in the population of CFUe, especially in the spleen, and (b) a less significant incre...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1985-08-01 00:00:00
abstract::An increasing amount of data provides strong evidence for the complex multifactorial control of primary hemopoietic functions. Here we present a new multicellular functional unit, the Hematon, isolated from the light-density floating fraction of normal human bone marrow (BM) aspirates. The Hematon is organized in a co...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1990-05-01 00:00:00
abstract:OBJECTIVE:Hematopoietic progenitor cells are a promising source for generation of genetically modified dendritic cells. A prerequisite for using these cells in therapeutic approaches is stable vector-mediated transgene expression during and after cell maturation. We investigated the expression of enhanced green fluores...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(01)00778-0
更新日期:2002-02-01 00:00:00
abstract::Similarly to other tissues, the bone marrow contains subsets of resident tissue macrophages, which are essential to maintain bone formation, functional hematopoietic stem cell (HSC) niches, and erythropoiesis. Pharmacologic doses of granulocyte colony-stimulating factor (G-CSF) mobilize HSC in part by interfering with...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2014.03.009
更新日期:2014-07-01 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::Committed erythroid progenitor cells (Colony Forming Units-Erythroid, CFU-E) have been studied in canine cyclic hematopoiesis (CH) utilizing a semi-solid methyl cellulose culture system. Erythroid colonies were stimulated by the addition of a standard volume of serum from normal dogs that had been phlebotomized and su...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1978-10-01 00:00:00
abstract::The prostaglandin E (PGE) enhancement of erythroid colony formation by human bone marrow erythroid progenitor cells (BFU-E) is mediated by a T8+ subset of lymphocytes. Medium was conditioned by bone marrow and blood T-lymphocytes and T-lymphocyte subsets (T8+, T8-, T4+, and T4- cells) in the absence or presence of PGE...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1987-08-01 00:00:00
abstract:OBJECTIVE:Morbidity and mortality occurring in patients with multiple myeloma, AL amyloidosis, and light chain deposition disease can result from the pathologic deposition of monoclonal immunoglobulin light chains (LCs) in kidneys and other organs. To reduce synthesis of such components, therapy for these disorders typ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2010.07.001
更新日期:2010-11-01 00:00:00
abstract::Multiple myeloma (MM) is a hematologic malignancy characterized as an abnormal proliferation and invasion of plasma cells into the bone marrow. Toll-like receptors (ТLRs) connect the innate and adaptive immune responses and represent a significant and potentially linking element between inflammation and cancer. When T...
journal_title:Experimental hematology
pub_type: 杂志文章,评审
doi:10.1016/j.exphem.2014.11.003
更新日期:2015-03-01 00:00:00
abstract::The megakaryocytopoiesis in rats was studied following a single dose of thio-TEPA to determine the mechanisms for the thrombocytopenia and subsequent recovery. The blood platelet number, platelet production (measured by 35S incorporation into platelets), mean platelet volume, and the number and DNA content of bone mar...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1986-03-01 00:00:00
abstract::Mast cell (MC)-fibroblast-immunocompetent cell interactions may play a role in the inflammatory and fibrotic processes present in chronic graft-vs.-host disease (cGVHD). Interactions between these cell types were examined in both murine and human cGVHD models. To this purpose, cell supernatants from mice or humans wit...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1997-03-01 00:00:00
abstract::Overexpression of immune-related genes is widely reported in myelodysplastic syndromes (MDSs), and chronic immune stimulation increases the risk for developing MDS. Aberrant innate immune activation, such as that caused by increased toll-like receptor (TLR) signaling, in MDS can contribute to systemic effects on hemat...
journal_title:Experimental hematology
pub_type: 杂志文章,评审
doi:10.1016/j.exphem.2015.05.016
更新日期:2015-08-01 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::Familial platelet disorder with propensity to acute myeloid leukemia (FPD/AML) is an autosomal dominant disease associated with a germline mutation in the RUNX1 gene and is characterized by thrombocytopenia and an increased risk of developing myeloid malignancies. We generated induced pluripotent stem cells (iPSCs) fr...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2015.05.004
更新日期:2015-10-01 00:00:00
abstract:OBJECTIVE:The retinoic acid receptors (RARs) alpha, beta2, and gamma regulate specific subsets of target genes during all-trans retinoic acid (RA) induced differentiation of F9 teratocarcinoma stem cells. The Tie1 gene exhibited reduced expression in RA-treated F9 RARgamma-/- cells as compared to wild-type (WT) by micr...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2007.12.016
更新日期:2008-05-01 00:00:00
abstract::Specific changes taking place in the erythroid tissue following depletion or replacement of androgens were studied in rats. The reduction of testosterone levels in blood of orchiectomized animals did occur in conjunction with a decline of erythrocyte glucose-6-phosphate (G6P) and lactate levels. No evidence of anemia ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1976-09-01 00:00:00
abstract:OBJECTIVE:CD34(+) cells, present within the bone marrow, have previously been shown to possess pancreatic endocrine potential. Based on this observation, we explored the capacity of CD34(+) cells derived in culture from the differentiation of human embryonic stem cells (hESC), for their in vivo pancreatic endocrine cap...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2010.03.002
更新日期:2010-06-01 00:00:00
abstract:OBJECTIVE:We previously demonstrated that CD8(+)/TCR(-) bone marrow cells facilitate engraftment of HSC in allogeneic recipients without causing graft-vs-host disease. Whether facilitating cells (FC) develop from T cells or represent a distinct lineage has not been determined. METHODS:In the present studies, we charac...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2004.07.011
更新日期:2004-10-01 00:00:00
abstract:OBJECTIVE:Intravenous (IV) injection is currently the normal method for transplanting hematopoietic cells. However, the problem of seeding efficiency and homing is relevant especially when a limited number of stem cells is available. Intra-bone marrow (IBM) injection of bone marrow cells (BMCs) may overcome this proble...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2004.05.026
更新日期:2004-08-01 00:00:00