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 genetic activity within the leukemia stem cell itself, mounting evidence indicates a significant contributory role played by marrow niche dysregulation. Furthermore, numerous instances of activating or inactivating germline mutations within marrow microenvironment cells have been shown to be sufficient for development of myelodysplastic syndrome, myeloproliferative neoplasm, and acute myeloid leukemia, even in the context of wild-type HSCs. Recent evidence suggests that targeting aberrant chemokine production from germline-mutated marrow stromal cells can potentially reverse the process of leukemogenesis. This elaborate interplay between the HSC population and the marrow microenvironment allows for a number of unique clinical possibilities in efforts to induce remission, enhance chemosensitivity, manage relapsed disease, and prevent leukemia development, both in de novo and germline mutation-associated leukemias, including the use of targeted cytokine/chemokine inhibitors, immune checkpoint blockade, CXCR4/CXCL12 axis antagonists, and combined allogeneic HSC and mesenchymal stem cell transplantation. In this review, we discuss the pathways underlying normal and abnormal bone marrow niche functioning, the relationship between germline mutations in the stem cell microenvironment and dysregulated hematopoiesis, and future clinical perspectives that may be particularly applicable to prevention and treatment of germline-associated leukemias.
journal_name
Exp Hematoljournal_title
Experimental hematologyauthors
Miller LH,Qu CK,Pauly Mdoi
10.1016/j.exphem.2018.07.001subject
Has Abstractpub_date
2018-10-01 00:00:00pages
17-26eissn
0301-472Xissn
1873-2399pii
S0301-472X(18)30633-7journal_volume
66pub_type
杂志文章,评审abstract：OBJECTIVE:The present study was designed to compare directly the frequency of circulating LTC-IC and E-LTC-IC mobilized in peripheral blood (PB) after chemotherapy supported by either G-CSF (PB-G) or GM-CSF (PB-GM) in comparison to steady-state bone marrow (BM) and PB (PB-ST) values in the same patients. MATERIALS AND...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(01)00762-7
更新日期：2002-01-01 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
abstract：:The cycle specific drug, hydroxyurea (HU), has previously been used to study the proliferative kinetics of various hemopoietic precursor cells such as granulocyte-macrophage precursors (CFUc) and multipotential stem cells (CFUs). We have investigated the kinetics of another hemopoietic precursor, a T-cell colony (CFUT...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1980-05-01 00:00:00
abstract：OBJECTIVE:To examine whether oncogenic Ras affects transforming growth factor (TGF)-beta-mediated cell-cycle arrest in hematopoietic cells and the downstream signal transduction pathway involved in the interference with TGF-beta-induced cell-cycle arrest. MATERIALS AND METHODS:Two leukemic cell lines bearing N-Ras(L61...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2005.04.006
更新日期：2005-07-01 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：:The statistical distribution of colony counts in the spleen colony assay was determined in C57BL/6 and C3H mice under varying conditions of the assay procedure. Assay mice were given syngeneic bone marrow cells from normal or irradiated donors. The mice were injected intravenously with marrow cells either immediately ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1977-11-01 00:00:00
abstract：:This study evaluated the usefulness of a matrix culture system, the artificial capillary culture system, for the growth of hematopoietic cells, the maintenance of CFUS and the collection of GM-CSF. The system was compared to monolayer, gelfoam sponge and Dexter liquid cultures. Monolayer cultures of adherent lymphohem...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1981-02-01 00:00:00
abstract：:The origin of spleen colony-forming units (CFUs) and fibroblastoid colony-forming cells (CFUF) repopulating the marrow of femurs subcutaneously implanted in syngeneic and semi-syngeneic mice was studied by making use of a chromosome marker for CFUs and a cytotoxicity test for CFUF. The CFUs present in implants during ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1983-02-01 00:00:00
abstract：:We have previously shown that CD33- CD34+ human marrow cells are capable of giving rise to colony-forming cells (CFC) in long-term marrow culture (LTMC) but are mainly depleted of progenitors that directly form colonies in semi-solid media. In contrast, the CD33+ CD34+ population contains most of the CFC but not the p...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1991-08-01 00:00:00
abstract：:Autotaxin (ATX) has been reported to act as a motility and growth factor in a variety of cancer cells. The ATX protein acts as a secreted lysophospholipase D by converting lysophosphatidylcholine (LPC) to lysophosphatidic acid (LPA), which signals via G-protein-coupled receptors and has important functions in cell mig...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2013.01.007
更新日期：2013-05-01 00:00:00
abstract：:The relative contributions of various organs to platelet production is controversial. In this study, serial histologic sections of bone marrow, spleen, liver, and lung from normal C57BL/6J mice and mice that had received three different agents which perturb normal murine thrombopoiesis (platelet antiserum, 5-fluoroura...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1997-07-01 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：:The switch/sugar nonfermenting (SWI/SNF) family of chromatin remodeling complexes have been implicated in normal hematopoiesis. The ARID2 protein is a component of the polybromo-associated BAF (PBAF), one of the two main SWI/SNF complexes. In the current study, we used a conditional Arid2 knockout mouse model to deter...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2020.12.004
更新日期：2020-12-17 00:00:00
abstract：:Antisera from rabbits immunized with murine macrophage colony-stimulating factor (CSF-1) were evaluated for cross-reactivity with human urine CSF-1. One cross-reactive antiserum was used to purify CSF from human urine. The IgG fractions from normal rabbit serum and the anti-CSF serum were bound to cyanogen bromide-act...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1989-01-01 00:00:00
abstract：:Immunoenzymatic (IE) staining for antigen detection on intact human bone marrow (BM) colonies grown in agar layers is described. The reliability of this method allowed a study of antigenic changes during myelomonocytic differentiation. Phenotypic analysis was carried out at different times using the following monoclon...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1988-06-01 00:00:00
abstract：OBJECTIVE:The aim of this study was to develop an animal model for human acute lymphoblastic leukemia (ALL) in which the kinetics and characteristics of leukemia can be sequentially monitored in individual mice. MATERIALS AND METHODS:NOD/SCID mice were inoculated intravenously with primary ALL. Progression of leukemia...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(00)00669-x
更新日期：2001-03-01 00:00:00
abstract：OBJECTIVE:Thrombopoietin stimulates megakaryopoiesis and platelet production by binding to its receptor, Mpl, on hematopoietic progenitor cells. Previously, a murine VB22B minibody for Mpl was shown to stimulate megakaryocyte colony formation in vitro and increase the platelet count in cynomolgus monkeys. In this study...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2011.05.001
更新日期：2011-08-01 00:00:00
abstract：OBJECTIVE:B-cell chronic lymphocytic leukemia is a heterogeneous disease with a pronounced variation in the clinical course. With the purpose of identifying genes that could be related to disease progression, we have performed gene expression profiling on B-CLL patients with an indolent disease and patients with a prog...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2005.05.007
更新日期：2005-08-01 00:00:00
abstract：:A method is described that permits the removal of hematopoietic cells and macrophages from mouse bone marrow cultures. The method is based on the difference in effect of extracellular ATP4- ions (ATP in the absence of divalent, complexing cations) on cells of hematopoietic origin, including macrophages, and of nonhema...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1994-02-01 00:00:00
abstract：:Normal human peripheral blood mononuclear cells (MNCs), particularly T lymphocytes (T cells), are a rich source of granulocyte-macrophage colony-stimulating factor (GM-CSF). Glucocorticoids are known to inhibit GM-CSF production in in vitro cultures of a human fibroblast cell line and in normal human blood monocytes a...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1998-12-01 00:00:00
abstract：:Rats with diets containing 0.2% propylthiouracil (PTU) throughout gestation had progeny with persistent cyanosis and high neonatal mortality. Histological and histochemical studies failed to reveal lung abnormalities in these pups. Studies of the blood of PTU-fed dams demonstrated that hemoglobin, packed cell volume, ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1982-01-01 00:00:00
abstract：:Human umbilical cord blood (CB) appears to be an exciting new source of transplantable stem cells for a variety of clinical conditions. In this study, we have attempted to further characterize the primitive progenitors in CB. First we analyzed the effects of early-acting growth factors on blast cell colony formation f...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1995-12-01 00:00:00
abstract：:In hematopoietic cell development, the transcriptional program is strictly regulated in a lineage- and stage-specific manner that requires a number of transcription factors to work in a cascade or in a loop, in addition to interactions with nonhematopoietic cells in the microenvironment. Disruption of the transcriptio...
journal_title：Experimental hematology
pub_type： 杂志文章,评审
doi：10.1016/j.exphem.2017.06.001
更新日期：2017-09-01 00:00:00
abstract：:We compared the kinetic recovery of lymphocytes and their subsets in two groups of patients submitted to allogeneic peripheral blood progenitor cell transplantation (allo-PBT): those receiving lymphocyte-depleted leukaphereses by positive selection of CD34+ cells (group 1, n = 18) and those receiving unmanipulated leu...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(98)00029-0
更新日期：1999-03-01 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：:Are the stem cells that survive graded doses of ionizing radiation as effective in restoring hematopoiesis in irradiated mice as transfused nonirradiated stem cells? This question was addressed by determining animal dose mortality and 10-day colony-forming units (CFU-S) survival curves and then replotting the percent ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1993-06-01 00:00:00
abstract：:Bone marrow endothelial cells are likely to play an important role in the homing of hematopoietic progenitor cells. In view of analyzing the interactions between endothelial cells and hematopoietic progenitor cells, we studied several methods of isolating endothelial cells from human bone marrow, including fluorescenc...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1995-01-01 00:00:00
abstract：:We have studied the effect of cortisone acetate (CA) on two important biological functions: (1) on NK cell-mediated cytotoxicity of B6D2F1 mice to T cell lymphoma, YAC-1 and (2) on hybrid resistance of mice to parental B6 bone marrow grafts. Results of our experiments have shown that 5 mg of CA administered i.p. was e...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1981-08-01 00:00:00
abstract：:Friend virus replicating target cells have been characterized by in vitro infection of bone marrow cells from DBA/2 mice after multiple injections of hydroxyurea (HU), after bleeding and/or hypertransfusion and after busulfan treatment. The concentration of CFUS, BFUE and CFUE in the cell suspension was correlated wit...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1982-05-01 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
