Abstract：
:Cancer stem cells (CSCs), including leukemia stem cells (LSCs), exhibit self-renewal capacity and differentiation potential and have the capacity to maintain or renew and propagate a tumor/leukemia. The initial isolation of CSCs/LSCs was in adult myelogenous leukemia, although more recently, the existence of CSCs in a wide variety of other cancers has been reported. CSCs, in general, and LSCs, specifically with respect to this review, are responsible for initiation of disease, therapeutic resistance and ultimately disease relapse. One key focus in cancer research over the past decade has been the development of therapies that safely eliminate the LSC/CSC population. One major obstacle to this goal is the identification of key mechanisms that distinguish LSCs from normal endogenous hematopoietic stem cells. An additional daunting feature that has recently come to light with advances in next-generation sequencing and single-cell sequencing is the heterogeneity within leukemias/tumors, with multiple combinations of mutations, gain and loss of function of genes, and so on being capable of driving disease, even within the CSC/LSC population. The focus of this review/perspective is on our work in identifying and validating, in both chronic myelogenous leukemia and acute lymphoblastic leukemia, a safe and efficacious mechanism to target an evolutionarily conserved signaling nexus, which constitutes a common "Achilles heel" for LSCs/CSCs, using small molecule-specific CBP/catenin antagonists.
journal_name
Exp Hematoljournal_title
Experimental hematologyauthors
Kim YM,Gang EJ,Kahn Mdoi
10.1016/j.exphem.2017.04.010subject
Has Abstractpub_date
2017-08-01 00:00:00pages
1-11eissn
0301-472Xissn
1873-2399pii
S0301-472X(17)30142-Xjournal_volume
52pub_type
杂志文章,评审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：:Umbilical cord blood (CB) is a rich source of hematopoietic stem cells (HSCs) with important applications in allogeneic stem cell transplantation. However, the low numbers of hematopoietic stem and progenitor cells (HSPCs) in banked units remain a major limitation. Protocols developed for HSPC expansion ex vivo or to ...
journal_title：Experimental hematology
pub_type： 杂志文章,评审
doi：10.1016/j.exphem.2015.04.011
更新日期：2015-07-01 00:00:00
abstract：:The ability to epigenetically reprogram differentiated somatic cells to pluripotency resulting in the discovery of induced pluripotent stem cells (iPSCs), has unlocked fundamental biologic insights into numerous genetic diseases. These insights have resulted from the key property of iPSCs to differentiate into all cel...
journal_title：Experimental hematology
pub_type： 杂志文章,评审
doi：10.1016/j.exphem.2019.01.002
更新日期：2019-03-01 00:00:00
abstract：:We have investigated the effect of hematopoietic cytokines on the survival of severe combined immune-deficient (SCID) mice that received a high dose of radiation. In this study, female SCID mice were irradiated at doses ranging from 500 to 600 cGy and then transplanted with 2 x 10(6) male Balb/c marrow cells. Groups o...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1994-02-01 00:00:00
abstract：:Induced pluripotent stem cells (iPS) derived from disease cells are expected to provide a new experimental material, especially for diseases from which samples are difficult to obtain. In this study, we generated iPS from samples from patients with primary and secondary myelofibrosis. The primary myelofibrosis cells h...
journal_title：Experimental hematology
pub_type： 临床试验,杂志文章
doi：10.1016/j.exphem.2014.03.010
更新日期：2014-09-01 00:00:00
abstract：:Serum erythropoietin (Epo) levels are depressed in anemic AIDS patients relative to controls. The basis for abnormal regulation of Epo has not been defined. The hepatoma cell line Hep3B produces Epo in response to hypoxia and serves as a model for the study of Epo regulation. Hep3B cells are infectible with human immu...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1993-05-01 00:00:00
abstract：:Several studies suggest that serum factors (thrombopoietins) regulate thrombopoiesis by altering the number, size, ploidy, and maturation rate of megakaryocytes (MK). Various in vivo systems have been used to quantitate these events. In this study, an in vitro system was developed to monitor terminal cytoplasmic matur...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1986-11-01 00:00:00
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...
journal_title：Experimental hematology
pub_type： 历史文章,杂志文章,评审
doi：10.1016/j.exphem.2020.01.008
更新日期：2020-03-01 00:00:00
abstract：:Chronic treatment of mice with transforming growth factor beta 1 (TGF-beta 1) resulted in a dose-dependent inhibition of erythropoiesis. Following 14 daily s.c. injections of 5 or 25 micrograms of TGF-beta 1, a significant degree of anemia was observed. In addition, erythroid progenitor cells were present in reduced n...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1992-09-01 00:00:00
abstract：OBJECTIVE:To study the early time course of engraftment of human mesenchymal stem cells in fetal sheep heart and determine the relative roles of proliferation and homing in formation of aggregates of human Purkinje fiber cells. METHODS:The human sheep xenograft model was utilized for these studies. Prior to injection ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2006.04.019
更新日期：2006-07-01 00:00:00
abstract：:Bone marrow-derived mast cell precursors form large mast cell colonies in methylcellulose and are designated as L-CFU-Mast. The effect of differentiated mast cells on recruitment and differentiation of L-CFU-Mast was investigated by using genetically mast cell-deficient WBB6F1-W/Wv mice. Giant granules of C57BL/6-bgJ/...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1990-03-01 00:00:00
abstract：:Improvement in diagnostic cytogenetic techniques has led to the recognition of an increasing number of leukemia-associated chromosomal translocations and inversions. These genetic lesions frequently are associated with the disruption of putative transcription factors and the production of hybrid transcripts that are i...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(99)00082-x
更新日期：1999-09-01 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：:Cultured guinea pig bone marrow megakaryocytes were found to secrete a 92-kd collagenase that was detected by digestion of gelatin in a polyacrylamide substrate gel assay. Neither casein or bovine serum albumin were digested by this enzyme. The enzyme is a neutral metalloprotease. Its secretion is increased by thrombi...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1990-08-01 00:00:00
abstract：:The presence of granulocyte colony-stimulating factor receptor (G-CSFR) in CD34+ hematopoietic progenitors is demonstrated by flow cytometry. Cord blood mononuclear cells (MNCs) contain about 1.09 +/- 0.2% CD34+ cells, 0.32 +/- 0.1% CD34+/G-CSFR+ (G-CSFR+) cells, and 0.77 +/- 0.1% CD34+/G-CSFR- (G-CSFR-) cells. The co...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1995-03-01 00:00:00
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 cli...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2021.01.003
更新日期：2021-01-20 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：:Vascular endothelial cells can affect hematopoiesis by releasing granulocyte-macrophage colony-stimulating factor (GM-CSF). In the present study, we show that GM-CSF production in murine aorta-derived vascular endothelial cells is regulated by two cytokines:interleukin-1 (IL-1), which induces the production of GM-CSF,...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1993-07-01 00:00:00
abstract：:A homogeneous population of mast cells was obtained by culturing bone marrow cells of WBB6F1(-)+/+ mice. The proliferation of the cultured mast cells in diffusion chambers was investigated to examine whether the diffusion chamber technique was applicable for study of the regulation of mast cell proliferation. WBB6F1-W...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1990-03-01 00:00:00
abstract：:Chronic lymphocytic leukemia (CLL) is a heterogeneous disease characterized by defects in the DNA damage response and apoptosis. Among the factors involved in these pathways, we focused on the enzyme poly(ADP-ribose) polymerase 1 (PARP1) and on its substrate Che-1 by evaluating their basal expression and functional ch...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2011.11.005
更新日期：2012-03-01 00:00:00
abstract：:Conditions that allow the growth of canine marrow cells in long-term marrow culture are described. The quality of the culture conditions was evaluated based on the weekly number of granulocyte-macrophage colony-forming units (CFU-GM) in the nonadherent cell fraction. Using this parameter, the highest number of CFU-GM ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1989-06-01 00:00:00
abstract：:We evaluated the expansion capacity of untreated and 5-fluorouracil (5-FU)-resistant peripheral blood stem cells (PBSC) after 7-day incubation with interleukin-1 (IL-1) plus IL-3 plus stem cell factor (SCF) or with medium alone. We found a significant increase in the proportion of CD34+ cells in the PBSC fraction resi...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1995-04-01 00:00:00
abstract：:It has been reported that bone marrow and serum of patients with aplastic anemia or chronic myeloproliferative disorders contain an abnormal concentration of cytokines. In the present study, we tried to isolate mouse bone marrow stromal cell lines that were stably transformed with a variety of cytokine genes and that ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1993-10-01 00:00:00
abstract：OBJECTIVE:Peripheral blood progenitor cells (PBPC) have been established as an alternative source of hematopoietic stem cells for allogeneic transplantation, but an increased incidence of both acute and chronic graft-vs-host disease (GVHD) has become apparent. We performed a prospective randomized trial comparing bone ...
journal_title：Experimental hematology
pub_type： 临床试验,杂志文章,多中心研究,随机对照试验
doi：10.1016/s0301-472x(03)00195-4
更新日期：2003-10-01 00:00:00
abstract：:Hematopoietic stem/progenitor cells (HSPCs) play important roles in fighting systemic infection as they supply immune cells in a demand-adapted manner. Various mechanisms govern HSPC responses to infection, including cytokine signaling, niche function, and direct sensing of pathogen-derived molecules by HSPCs themselv...
journal_title：Experimental hematology
pub_type： 杂志文章,评审
doi：10.1016/j.exphem.2015.11.008
更新日期：2016-02-01 00:00:00
abstract：:Functional recovery of the immune system is critical for long-term survival in hematopoietic stem cell transplant recipients. In this study, two donor-recipient allogeneic transplant settings (haploidentical and fully mismatched) are used to investigate the functional activity of donor-derived B and T cells in animals...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(00)00554-3
更新日期：2000-12-01 00:00:00
abstract：OBJECTIVE:To investigate the mechanisms of antiproliferative effect induced by the mammalian target of rapamycin (mTOR) inhibitor temsirolimus in mantle cell lymphoma (MCL). MATERIALS AND METHODS:The antiproliferative effect of temsirolimus on three well-defined MCL cell lines was examined by the MTS assay. Induction ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2007.12.008
更新日期：2008-04-01 00:00:00
abstract：:The use of neonatal instead of fetal calf serum, as a constituent of the culture medium, confronted the authors with the problem of toxicity in the fetal liver cell erythropoietin assay. Tested human sera were toxic at rather low concentrations. Heating the human sera for 30 min at 56 degrees C abolished the toxicity....
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1976-05-01 00:00:00
abstract：:We have studied the ability of subpopulations of hemopoietic stem cells, obtained from murine bone marrow using elutriation and multiparameter sorting, to establish and maintain hemopoiesis following their deposition on irradiated stromal layers of long-term bone marrow cultures. Two fractions were obtained that diffe...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1990-09-01 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
