Abstract：
:After initially successful chemotherapy, relapse frequently jeopardizes the outcome of patients with acute leukemia. Because of their adverse characteristics of self-renewal and dormancy, leukemia stem cells have been hypothesized to play a critical role in resistance to antiproliferative chemotherapy and the development of relapse. The high abundance of stem-like cells in acute lymphoblastic leukemia (ALL), however, suggests that not all leukemia-initiating cells carry these adverse characteristics, complicating the biological characterization of relapse-inducing cells in this malignancy. Here, we review sources of therapy resistance and relapse in acute leukemias, which include tumor cell plasticity and reversible characteristics. We discuss the development of patient-derived mouse models that are genetically engineered to mimic long-term dormancy and minimal residual disease in patients. These models allow the tracking and functional characterization of patient-derived ALL blasts that combine the properties of long-term dormancy, treatment resistance, and stemness. Finally, we discuss possible therapeutic avenues to target the functional plasticity of leukemia-initiating cells in ALL.
journal_name
Exp Hematoljournal_title
Experimental hematologyauthors
Senft D,Jeremias Idoi
10.1016/j.exphem.2018.09.006subject
Has Abstractpub_date
2019-01-01 00:00:00pages
1-10eissn
0301-472Xissn
1873-2399pii
S0301-472X(18)30807-5journal_volume
69pub_type
杂志文章,评审abstract：:Progress of age-related hematopoietic diseases such as myelodysplastic syndrome has previously been linked to enhanced levels of reactive oxygen species (ROS). Uncoupling protein 2 (UCP2) was found to reduce mitochondrial ROS production through uncoupling of the respiratory chain. The impact of UCP2 loss and elevated ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2016.08.003
更新日期：2016-11-01 00:00:00
abstract：:Collagen gel was used as a substance for the assay of human granulocyte-macrophage colony-forming units (CFUc). The number of colonies formed in collagen gel was consistently higher than that in a conventional soft-agar system. In six out of eight experiments, the difference was statistically significant. Whole perman...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1984-05-01 00:00:00
abstract：OBJECTIVE:The cause of delayed hematopoietic reconstitution after umbilical cord blood transplantation (UCBT) remains controversial. We hypothesized that hematopoietic stem/progenitor cells (HS/PCs) from UCB have some defects of the homing-related molecules responsible for their slow engraftment. MATERIALS AND METHODS...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2003.08.016
更新日期：2003-12-01 00:00:00
abstract：:Allogeneic bone marrow recipients exhibit a complex and multifactorial immunodeficiency affecting numerous effector functions for various periods of time. In order to evaluate their Fc-mediated monocyte-macrophage (MM) function we studied the clearance of IgG-coated Rh-positive erythrocytes (EA) in healthy control sub...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1989-10-01 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：: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：: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：:Different human hematopoietic cell lines were analyzed for the presence of interleukin 6 (IL-6) and IL-6 receptor (IL-6-R). Both IL-6 mRNA and secreted active IL-6 protein were detectable in untreated cell lines with erythroid or megakaryoblastic features (K562, HEL, KU 812, MEG-01, and Dami), but they were not expres...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1991-01-01 00:00:00
abstract：:The selection of chemotherapy regimen for elderly patients with acute myeloid leukemia (AML) remains challenging. Here, we report that granulocyte colony-stimulating factor (G-CSF) upregulates the expression of microRNA (miR)-146a in a nuclear factor kappaB-dependent manner, leading to direct decreases in the expressi...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2018.09.002
更新日期：2018-12-01 00:00:00
abstract：:We analyzed the accessory function of malignant B cells from non-Hodgkin's lymphomas (NHLs). Among the 70 samples of malignant B cells included, four patterns of expression of the costimulatory molecules CD80 and CD86 were distinguished (+/+, +/-, -/+ and -/-). In two-thirds of the cases, CD80, CD86, or both were expr...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(98)00059-9
更新日期：1999-03-01 00:00:00
abstract：:Agar cultures of human bone marrow cells stimulated by cord plasma or irradiated cord blood feeder layers demonstrated the presence of a multilineage hemopoietic growth factor in cord blood. When bone marrow cultures stimulated with giant cell tumor-conditioned medium (GCT-CM) were supplemented with this cord blood-de...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1986-09-01 00:00:00
abstract：:The heat sensitivity at 42 degrees, 43 degrees and 44 degrees C of various hematopoietic subsets in murine bone marrow (MRA, CFU-S-12, CFU-S-8, CFU-GM, BFU-E and CFU-E) was investigated in order to determine whether there is a relationship between heat sensitivity and the position of cells within the stem cell hierarc...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1993-05-01 00:00:00
abstract：:Sphingosine, a sphingolipid breakdown product, has been proposed as an apoptosis-inducing agent. In this study, we examined the effect of sphingosine in bcl-2-overexpressing cells compared with cells that do not express the bcl-2 gene. The human erythroleukemic cell line TF1, which lacks bcl-2 expression, was easily i...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1998-11-01 00:00:00
abstract：OBJECTIVE:The purpose of this study was to evaluate the repopulating properties of bone marrow (BM) from mice irradiated during embryonic and adult stages of development. MATERIALS AND METHODS:Four-day-old embryos, 17-day-old fetuses, and 12-week-old mice were irradiated with of 1 or 3 Gy of x-rays. At 3 and 9 months ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(99)00128-9
更新日期：2000-01-01 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：:Lymphatic leukemia L1210-bearing semisyngeneic Balb/c x DBA/2Wf F1 (CD2F1) mice were subjected to chemoradiotherapy (2 x 100 mg/kg of cyclophosphamide i.p. and 1000 cGy of total body irradiation) and reconstitution with 10(7) syngeneic bone marrow cells i.v. The bone marrow obtained from leukemic mice was previously e...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1988-10-01 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：OBJECTIVE:This study was focused on studying the role of Sca-1 (Ly-6 A/E) in hematopoietic stem/progenitor cell self-renewal, activation, and lineage fate. MATERIALS AND METHODS:Sca-1(-/-) bone marrow cells were transplanted into wild-type recipient mice and assessed for self-renewal activity and lineage choice. In ad...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2005.04.001
更新日期：2005-07-01 00:00:00
abstract：:In different types of myeloid leukemia, increased formation of reactive oxygen species (ROS) has been noted and associated with aspects of cell transformation, including the promotion of leukemic cell proliferation and migration, as well as DNA damage and accumulation of mutations. Work reviewed in this article has re...
journal_title：Experimental hematology
pub_type： 杂志文章,评审
doi：10.1016/j.exphem.2016.08.008
更新日期：2016-12-01 00:00:00
abstract：:Somatic mutations of calreticulin (CALR) have been observed in many cases of essential thrombocythemia (ET) or primary myelofibrosis that harbor non-mutated Janus kinase 2 (JAK2). CALR mainly localizes within the endoplasmic reticulum lumen, but a small fraction of the total CALR pool is distributed over the cell surf...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2016.05.001
更新日期：2016-09-01 00:00:00
abstract：OBJECTIVE:The primary objective of this study was to identify and clone the first nonmammalian thrombopoietin (TPO), chicken TPO, and its receptor c-Mpl for the purpose of characterizing their activities both in vitro and in vivo. MATERIALS AND METHODS:Chicken TPO was cloned using the methods of reverse transcriptase ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2007.12.001
更新日期：2008-04-01 00:00:00
abstract：OBJECTIVE:Our previous studies have demonstrated differentially expressed genetic signature patterns in adult peripheral blood (APB) monocytes (Mos) vs cord blood (CB) Mos. MATERIALS AND METHODS:In this study, we examined the differential gene expression profiles of APB vs CB immature dendritic cells (iDCs) and mature...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2009.07.010
更新日期：2009-10-01 00:00:00
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：:To help establish an effective gene therapy protocol for patients with congenital metabolic diseases, we evaluated retrovirus-mediated transduction and long-term (LT) expression of the NeoR gene in cryopreserved and thawed CD34+ cells purified from granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blo...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1997-08-01 00:00:00
abstract：OBJECTIVES:Macrophage inflammatory protein-1alpha (MIP-1alpha), an osteoclast (OCL) stimulatory factor produced by primary multiple myeloma (MM) cells, increases bone destruction and tumor burden in murine models of MM. Several chemokine receptors (CCR1, CCR5, and CCR9) mediate the effects of MIP-1alpha. In this study,...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2004.11.015
更新日期：2005-03-01 00:00:00
abstract：:It is becoming increasingly clear that the adeno-associated virus 2 (AAV)-based vector system may prove to be useful for high-efficiency gene transfer in human cells as well as for potential gene therapy in humans. A recombinant AAV vector containing the gene for a human hematopoietic growth factor, granulocyte-macrop...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1995-11-01 00:00:00
abstract：:The mechanism of accelerated erythropoiesis under the hypoxic conditions of high altitude (HA) remains largely obscure. Here, we investigated the potential role of bone marrow (BM) T cells in the increased production of erythrocytes at HA. We found that mice exposed to a simulated altitude of 6,000 m for 1-3 weeks exh...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2014.04.007
更新日期：2014-09-01 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：:Tumor necrosis factor alpha (TNFalpha) is thought to contribute to the blunted erythropoietin (Epo) production in inflammatory diseases. The present study was carried out to find out as to whether the 55 kD (TNF-RI) or the 75 kD (TNF-RII) receptor is responsible for the TNFalpha-induced inhibition of hepatic Epo synth...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(98)00054-x
更新日期：1999-02-01 00:00:00
abstract：:Increasing evidence points to endoglin (Eng), an accessory receptor for the transforming growth factor-β superfamily commonly associated with the endothelial lineage, as an important regulator of the hematopoietic lineage. We have shown that lack of Eng results in reduced numbers of primitive erythroid colonies as wel...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2012.06.007
更新日期：2012-10-01 00:00:00
