Abstract：
OBJECTIVE:The evolutionarily conserved Kit receptor is vital for function of hematopoietic stem cells (HSC). Kit(W-41) (W-41) and Kit(W-42) (W-42) are single residue changes in the KIT intracellular phosphotransferase domain, while Kit(W-v) (W-v) is a single residue change in the ATP binding domain. This study tests how each mutation affects HSC function. METHODS:Cells in mutant and C57BL/6J(+/+) blood and marrow were compared. Overall HSC function was measured by competitive repopulation. Functions of specific progenitor populations were tested with stage-specific competitive repopulation and standard colony-forming unit assays. RESULTS:Bone marrow cells from these Kit mutants are severely defective at reconstituting peripheral blood lineages and bone marrow of irradiated recipients, when compared to +/+ control marrow. These defects increased with time. Marrow from W-41/+ and W-v/+ functions similarly but better than marrow from W-41/W-41 and W-42/+, to repopulate the erythroid and lymphoid lineages. Long-term (LT) and short-term (ST) HSC from W-v/+, W-41/W-41, and W-42/+ are more defective at reconstituting bone marrow than LT- and ST-HSC from W-41/+ and +/+. Common myeloid progenitor (CMP) cells from W-42/+ and W-41/W-41 are more defective at producing spleen colonies than CMP from W-v/+ and W-41/+. CONCLUSION:Heterozygous Kit mutants with little or no apparent anemia exhibit surprisingly large defects in overall HSC function. Multiplying the fractional defects in LT-HSC, ST-HSC, and CMP can account for overall effects of W-v/+, but does not completely account for the defects observed with W-41/+, W-42/+, and W-41/W-41.
journal_name
Exp Hematoljournal_title
Experimental hematologyauthors
Sharma Y,Astle CM,Harrison DEdoi
10.1016/j.exphem.2006.10.001subject
Has Abstractpub_date
2007-02-01 00:00:00pages
214-220issue
2eissn
0301-472Xissn
1873-2399pii
S0301-472X(06)00639-4journal_volume
35pub_type
杂志文章abstract：:Acute myeloid leukemia (AML) is a disease with a poor prognosis. It has been demonstrated that AML cells express vascular endothelial growth factor (VEGF) as well as Flt-1 and KDR, resulting in an autocrine pathway for cell survival. PTK787/ZK 222584 is a new oral antiangiogenic molecule that inhibits tyrosine kinase ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2009.03.001
更新日期：2009-06-01 00:00:00
abstract：:Data in this report determined the effect of a single injection of recombinant interleukin 1 alpha (rIL-1) prior to irradiation of B6D2F1 mice on the recovery of colony-forming cells (CFC) at early and late times after sublethal and lethal doses of radiation. Injection of rIL-1 promoted an earlier recovery of mature c...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1988-10-01 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：OBJECTIVE:A multi-step statistical strategy was applied to quantify individual and interactive effects of cytokines on megakaryopoiesis and to determine the concentration of the selected cytokines that optimize ex vivo megakaryocyte (MK) expansion, maturation, and platelet production in stromal- and serum-free conditio...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2005.06.020
更新日期：2005-10-01 00:00:00
abstract：OBJECTIVE:We have previously reported immunity to donor antigens following in utero transplantation (IUT) of cytokine-stimulated allogeneic hematopoietic stem cells (sca(+)/lin(-)) (day 9 of gestation). Transplanted mice showed accelerated rejection of donor skin grafts and high anti-donor cytotoxic response, a finding...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(02)00803-2
更新日期：2002-06-01 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：:Erythropoiesis requires large amounts of iron for hemoglobin synthesis. There are two sources of iron for erythropoiesis, dietary and stored iron; however, their relative contributions to erythropoiesis remain unknown. In this study, we used the stable iron isotope (57)Fe to quantify synthesis of hemoglobin derived fr...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2016.02.005
更新日期：2016-06-01 00:00:00
abstract：OBJECTIVE:To investigate the role of perforin-mediated cell apoptosis in murine models of immune-mediated bone marrow (BM) failure. MATERIALS AND METHODS:We compared C57BL/6J (B6) mice carrying a perforin gene deletion (Prf(-/-)) with wild-type (WT) controls for cellular composition in lymphohematopoietic tissues. Lym...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2008.12.001
更新日期：2009-04-01 00:00:00
abstract：:Acute disseminated intravascular coagulation (DIC) is a life-threatening condition that may be encountered in many situations, especially in cases of shock with uncontrollable hemorrhage. Anisodamine, an alkaloid extracted from a Chinese herb, is well known for its dramatic therapeutic effect on DIC. Sixty male rabbit...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1987-01-01 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：: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：:Hematopoiesis in continuous bone marrow culture is dependent upon close-range interaction between hematopoietic cells and marrow-derived adherent cells. The latter have been shown to include a significant proportion of fibroblastic elements, synthesizing the attachment protein fibronectin. The role of fibronectin in c...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1983-02-01 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：:Megakaryocytes have been implicated in the micro-environmental abnormalities associated with fibrosis and hematopoietic failure in the bone marrow (BM) of primary myelofibrosis (PMF) patients, the Philadelphia-negative myeloproliferative neoplasm (MPN) associated with the poorest prognosis. To identify possible therap...
journal_title：Experimental hematology
pub_type： 临床试验,杂志文章
doi：10.1016/j.exphem.2019.10.001
更新日期：2019-11-01 00:00:00
abstract：:To assess the thrombopoietic activity of erythropoietin (Epo) in vivo in mice, we consecutively administered recombinant human Epo (rEpo) i.p. to intact and splenectomized mice for varying time intervals. Recombinant human Epo increased platelet counts in a dose-dependent fashion in a short-term trial for 5 days. An 1...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1992-02-01 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：: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：:In vitro exposure of murine hematopoietic stem cells (HSCs) to cell cycle-inducing cytokines has been shown to result in a defect in the ability of these cells to engraft. We used a porcine microvascular endothelial cell (PMVEC) line in conjunction with exogenous interleukin (IL)-3, IL-6, granulocyte-macrophage colony...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1998-09-01 00:00:00
abstract：:The granulocyte defects of Chediak-Higashi syndrome (CHS) include neutropenia, characteristic giant lysosomal granule morphology, and functionally abnormal cell motility, degranulation, and bacterial killing. Findings of elevated levels of adenosine 3', 5' cyclic monophosphate nucleotide (cAMP) and of concanavalin A (...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1985-02-01 00:00:00
abstract：OBJECTIVE:We monitored cytokine-secreting cells using an enzyme-linked immunospot (ELISPOT) assay in a prospective study to assess the cytokine network after transplantation. PATIENTS AND METHODS:Peripheral blood mononuclear cells were collected from 23 patients who received allogeneic stem cell transplantation, from ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2004.10.009
更新日期：2005-02-01 00:00:00
abstract：:Colonies containing blast cells (greater than 95%) have been characterized in 14-day cultures of normal murine bone marrow or spleen cells, stimulated by an adherent bone marrow cell line, B.Ad. These blast cell colonies occurred at a frequency of 1-2 per 2.5 X 10(4) bone marrow or 2.5 X 10(5) spleen cells and contain...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1987-10-01 00:00:00
abstract：:Mouse hematopoietic stem cells (HSCs) are highly enriched in the rare (approximately 0.05%) Thy-1.1(lo)Lin(-/lo)Sca-1+ fraction of hematopoietic tissues. It has been demonstrated that Thy-1.1(lo)Lin(-/lo)Sca-1+ cells are the only HSCs in C57BL/Ka-Thy-1.1 bone marrow. In this study, we separated C57/Ka-Thy-1.1 bone mar...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1996-04-01 00:00:00
abstract：:Haemopoietic regeneration was studied following x-irradiation and transplantation of bone marrow from either normal or hydroxyurea-treated donor mice, to ascertain the contribution of proliferating progenitor cells to regeneration. With transplantation of equivalent numbers of CFU-S, total DNA and 3HTdR uptake into DN...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1977-09-01 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：:Mice of the RF strain are unusually susceptible to the development of leukemia, both spontaneously and after whole body irradiation. Cell culture and transplantation techniques were used to study the proliferative capacity of hematopoietic tissues of these mice. The growth characteristics of granulopoietic cells of yo...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1980-09-01 00:00:00
abstract：:A simple two-step procedure has been developed for the production of human urinary erythropoietin suitable for tissue culture use. Lyophilized human urinary protein was fractionated by phenyl-Sepharose chromatography, the erythropoietin binding in 2 M lithium chloride and being eluted by an ascending linear gradient t...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1985-09-01 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：:Using an accurate technique for staining and scoring soft agar cultures, this study defines the incidence of circulating CFUEOS in normal donors. With whole mononuclear cells as the source of colony stimulating factor (CSF) and fetal calf serum, 49.6% +/- 3.5 of the colonies were eosinophilic; with human placental con...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1982-03-01 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：:Arsenic trioxide (As2O3) has been demonstrated to be effective for the treatment of acute promyelocytic leukemia (APL) and to inhibit proliferation and produce apoptosis in the APL cell line NB4. To determine if As2O3 might be useful for the treatment of other lineages, we investigated the effects of As2O3 on viabilit...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(99)00014-4
更新日期：1999-05-01 00:00:00
