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：:Pretreatment of mice with 5-fluorouracil (5-FU) depletes total marrow cellularity but leaves a residual population of cells with enhanced regenerative capability. Using the long-term Dexter liquid culture system, we studied the effects of 5-FU on murine marrow cells and their production of pluripotent stem cells (CFU-...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1986-03-01 00:00:00
abstract：:Exposure to low levels of x-irradiation (50R) followed by phlebotomy (50% blood volume) one month post-irradiation, resulted in identifiable alterations of the erythropoietic status of the rat. The red cell indices revealed a decrease in mean corpuscular volume and an increase in mean corpuscular hemoglobin concentrat...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1975-11-01 00:00:00
abstract：:This report presents the results of studies using long-term bone marrow cultures (LTBMC) of human bone marrow cells to investigate the effect of HIV-1 on in vitro hematopoiesis. Confluent stromal cell layers established from human bone marrow cells were irradiated to eliminate residual hematopoietic progenitor cells a...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1994-12-01 00:00:00
abstract：:We have found that treatment of B6SUtA1 cells with 0.01% glutaraldehyde transformed them into mechanically resistant spheres, thereby making it possible to use these high interleukin 3 (IL-3) receptor-bearing cells as a solid phase reagent suitable for the large scale purification of murine IL-3 (mIL-3). Using this te...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1989-11-01 00:00:00
abstract：:Reports that cells from neonatal animals produce CFU-E in response to erythropoietin (Ep) at doses lower than are required by adults indicated that young mice would provide a good system to study the hormone response of erythropoietic progenitors. Studies presented here confirm the increased Ep responsiveness until 3-...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1984-08-01 00:00:00
abstract：OBJECTIVE:About one third of patients requiring allogeneic hematopoetic stem cell transplantation (HSCT) would not find a matched sibling or alternative donor. Allogeneic HSCT from matched unrelated and mismatched donors carries an increased risk of graft-vs-host disease (GVHD) and transplant-related mortality (TRM). ...
journal_title：Experimental hematology
pub_type： 临床试验,杂志文章
doi：10.1016/j.exphem.2008.03.011
更新日期：2008-08-01 00:00:00
abstract：:The spleen colony assay, three agar colony assays and two repopulating assays have been employed to measure the effect of single doses of adriamycin, methyl CCNU, 60CO gamma-rays, vinblastine and repeated injection of cytosine arabinoside on early haemopoietic precursors. The results show that there is no consistent c...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1978-01-01 00:00:00
abstract：:We have studied the in vivo spleen colony-forming ability and marrow repopulating ability of murine bone marrow cells differing in mitochondrial activity. Following centrifugal elutriation the cells were sorted on the basis of rhodamine-123 fluorescence intensity within a predetermined light scatter window. It is show...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1989-03-01 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：UNLABELLED:OBJECTIVE, METHODS, AND RESULTS: To reduce the period of posttransplant neutropenia and related early morbidity and mortality of cord blood (CB) transplants, we assessed the feasibility of co-infusion of a low number of highly purified peripheral blood CD34+ cells from a related haploidentical donor with a C...
journal_title：Experimental hematology
pub_type： 临床试验,杂志文章
doi：10.1016/s0301-472x(03)00067-5
更新日期：2003-06-01 00:00:00
abstract：:Human cord blood or bone marrow cells expressing the CD34 surface antigen include a population of pluripotent progenitors. We identified and isolated a subpopulation of cells coexpressing CD34 and c-kit, a transmembrane receptor with tyrosine kinase activity. Novel monoclonal antibodies (16A6, 14A3, 3D6) directed agai...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1993-01-01 00:00:00
abstract：OBJECTIVE:TGF-beta1 is a powerful inhibitor of erythropoiesis. However, its mechanisms of action are not fully elucidated yet at the cellular level. In this work we have studied the effects of TGF-beta on UT-7 cell survival, proliferation and differentiation. MATERIALS AND METHODS:UT-7 cell line is strictly dependent ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(99)00155-1
更新日期：2000-03-01 00:00:00
abstract：:The present studies evaluated effects of recombinant human (rhu) and murine (rmu) flt3 ligand (flt3-L) on colony formation by subsets of myeloid stem and progenitor cells present in low-density (LD) and cell-sorted CD34 hu cord blood (CB) and bone marrow (BM) cells and unseparated mu BM cells. By itself, flt3-L had we...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1995-09-01 00:00:00
abstract：:The relationship between the hematopoietic stem cell (HSC) population and its surrounding bone marrow microenvironment is a rapidly evolving area of research. Normal HSC processes rely heavily on a complex communication network involving various marrow niches. Although leukemogenesis largely results from abnormal gene...
journal_title：Experimental hematology
pub_type： 杂志文章,评审
doi：10.1016/j.exphem.2018.07.001
更新日期：2018-10-01 00:00:00
abstract：:Together, interleukin-1 alpha (IL-1 alpha) and IL-1 beta primed human neutrophils for enhanced release of superoxide (O2-) stimulated by chemotactic peptide, chemokine, and plant lectin, and alone, each triggered O2- release in a dose-dependent manner. The maximal priming and triggering effect was obtained by high con...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1995-07-01 00:00:00
abstract：:The first blood cells observed in the embryo are large nucleated erythroblasts generated in blood islands of the extraembryonic yolk sac. These unique red cells have been termed primitive because of their resemblance to nucleated erythroblasts of nonmammalian species. It is now widely assumed that hematopoiesis in the...
journal_title：Experimental hematology
pub_type： 杂志文章,评审
doi：10.1016/j.exphem.2005.06.012
更新日期：2005-09-01 00:00:00
abstract：:The aim of this work was to monitor the functional and phenotypic variations of natural killer (NK) cells in seven children with stage IV neuroblastoma (NB) treated with recurrent 5-day cycles of interleukin-2 (IL-2) at a dose of 18 x 10(6) IU/m2/d by continuous intravenous infusion. All patients who entered the study...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1995-12-01 00:00:00
abstract：:We recently reported a method for long-term in vitro culture of human monocytes with maintenance of functional and morphological homogeneity. We have now used microexudate-coated flasks to improve both the plating efficiency and the purity of these cultures. The technique is based on pregrowth of BHK cells that presum...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1984-03-01 00:00:00
abstract：:Phagocytic cells are characterized by their ability to generate superoxide anions upon activation by appropriate stimuli. UM384, a myelomonocytic cell line, was shown to be defective in this oxidase activity as measured by nitroblue tetrazolium or cytochrome c reduction. Cytochrome b558, a unique pigment present in ph...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1993-07-01 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：: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：: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：:In vitro colony formation by erythroid progenitors from the bone marrow was studied in 42 patients with a myelodysplastic syndrome using both a standard assay for growing erythroid colonies and an assay designed for growing megakaryocyte colonies. In the standard assay 5 patients had normal numbers of erythroid burst-...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1990-11-01 00:00:00
abstract：OBJECTIVE:Generation and expansion of pluripotent unrestricted somatic stem cells (USSCs) and mesenchymal cells (MSCs) from human cord blood as well their functional characterization were assessed. METHODS:USSC generation was initiated from fresh and cryopreserved cord blood (CB). Culture conditions and functional ass...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2006.07.011
更新日期：2006-11-01 00:00:00
abstract：:High-dose chemotherapy followed by autologous bone marrow transplantation (ABMT) in the treatment of malignancies is often associated with immune deficiency following transplantation, possibly contributing to tumor relapse or fatal infection. Interleukin 2 (IL-2), which enhances major histocompatibility complex (MHC)-...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1992-09-01 00:00:00
abstract：:In the present study we investigated the absolute numbers of granulocytic progenitor cells (CFUc) in the spleens of adult normal dogs, their differentiation pattern and also their proliferative state. Between 10 and 40 times as many CFUc were found in the spleens of individual dogs as were present in the total blood v...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1980-09-01 00:00:00
abstract：:Lifelong blood production is ensured by a population of rare and largely quiescent, long-lived hematopoietic stem cells (HSCs). The advent of single-cell technologies has recently highlighted underlying molecular and functional heterogeneity within the HSC pool. Despite heterogenous HSC behaviors, quiescence remains a...
journal_title：Experimental hematology
pub_type： 杂志文章,评审
doi：10.1016/j.exphem.2020.11.003
更新日期：2020-12-01 00:00:00
abstract：:The circadian and circannual rhythms of committed stem cells (CFUc) were investigated by using the agar colony technique. There was a marked circadian rhythmicity, with variations between maximum and minimum colony yields of 2-5.5 times; such variations could also be seen throughout the year. A phase shift was observe...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1984-01-01 00:00:00
abstract：OBJECTIVE:Nonmyeloablative conditioning regimens for marrow transplantation are desirable in many settings. Because repeated doses of the antimetabolite 5-fluorouracil (5-FU) decreases marrow long-term repopulating ability (LTRA) upon transplantation into lethally irradiated hosts, we hypothesized that mice given seque...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2004.08.007
更新日期：2004-12-01 00:00:00
abstract：:We have assessed the potential use of the mononuclear cell (MNC) content as the sole assessment of graft quality in 35 patients receiving BEAM (carmustine, etoposide, cytosine arabinoside, melphalan) chemotherapy and autologous peripheral blood progenitor cell (PBPC) transplantation for malignant lymphoma. PBPCs were ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1995-12-01 00:00:00
