Abstract:
OBJECTIVE:We studied two adult brothers with severe congenital thrombocytopenia in order to determine the genetic etiology of their inherited disorder. Despite the absence of eczema or immunodeficiency, a mutation of the Wiskott-Aldrich syndrome (WAS) gene was suspected because of the presence of microthrombocytes. MATERIALS AND METHODS:Peripheral blood was obtained for characterization of hematopoietic cells and megakaryocyte progenitors. The coding region of the WAS gene was fully sequenced, and expression of the Wiskott-Aldrich syndrome protein, WASP, was evaluated by immunoblotting. The ability of WASP to physically associate with the WASP-interacting protein, WIP, was tested by yeast and mammalian two-hybrid techniques. RESULTS:In addition to thrombocytopenia, our investigation revealed an increased frequency of peripheral megakaryocyte progenitors (CFU-Mk) and incomplete cytoplasmic maturation by electron microscopy. Sequencing the WAS gene revealed a single base mutation, resulting in substitution of proline for arginine 138 (i.e., Arg138Pro). Immunoblotting demonstrated reduced expression of the mutant WAS protein, and we showed that the Arg138Pro mutation significantly, but incompletely, disrupts WASP-WIP interaction. CONCLUSIONS:In this pedigree, X-linked thrombocytopenia is caused by a rare mutation in the fourth exon of the WAS gene. WASP levels are reduced in lymphocyte cell lines derived from the affected individuals. Furthermore, the mutation significantly but incompletely disrupts WASP-WIP interaction, whereas substitution of alanine or glutamic acid residues at the same position does not. This raises the possibility that protein-protein interaction and WASP stability are related properties.
journal_name
Exp Hematoljournal_title
Experimental hematologyauthors
Luthi JN,Gandhi MJ,Drachman JGdoi
10.1016/s0301-472x(02)01023-8keywords:
subject
Has Abstractpub_date
2003-02-01 00:00:00pages
150-8issue
2eissn
0301-472Xissn
1873-2399pii
S0301472X02010238journal_volume
31pub_type
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journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2009.01.006
更新日期:2009-05-01 00:00:00
abstract::Washed canine platelets were shown to express a significant level of von Willebrand factor (vWf). Canine platelet vWf differed from canine plasma vWf by the absence of satellite bands associated with each multimer when resolved by SDS-agarose gel electrophoresis. Expression and multimeric composition of canine platele...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
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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::HIV-derived lentiviral vectors have been used widely to transduce non-dividing cells, such as hematopoietic stem cells (HSCs), in the setting of gene therapy. In this study, we screened lentiviral vectors for their ability to drive expression of the murine MHC class II chaperone, invariant chain (Ii) and a GFP reporte...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2013.07.002
更新日期:2013-11-01 00:00:00
abstract::Mantle cell lymphoma (MCL) affects approximately 4500 patients/year in the US and demonstrates a male to female ratio of approximately 4:1. While the pathobiology underlying this ratio is unknown, the hematopoietic system is characterized by sex-related differences in androgen receptor (AR) expression, leading us to h...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2017.01.001
更新日期:2017-05-01 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:OBJECTIVE:Several requirements need to be fulfilled for clinical use of expanded hematopoietic stem cells (HSCs). Because most cord blood (CB) samples are frozen in single bags and only an aliquot ( approximately 25%) of the blood can be expanded, the thawing and refreezing of samples must be validated in the current E...
journal_title:Experimental hematology
pub_type: 杂志文章,多中心研究
doi:10.1016/j.exphem.2007.08.030
更新日期:2008-02-01 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::The effects of intraperitoneal Ehrlich ascites tumor (ET) growth on the kinetics of hemopoietic stem cells in the host bone marrow were studied using the spleen colony and the soft agar culture techniques. There is a decrease in spleen colony forming capacity of bone marrow of ET bearing mice, whereas in vitro assays ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1978-05-01 00:00:00
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journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(02)01009-3
更新日期:2003-01-01 00:00:00
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journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2013.03.009
更新日期:2013-08-01 00:00:00
abstract:OBJECTIVE:Identification of genomic lesions in progenitor cells of patients with myelodysplastic syndrome (MDS) could lead to the discovery of new disease-specific genes and may be of prognostic value. MATERIALS AND METHODS:We carried out a genome-wide mapping of DNA from CD34+ cells of MDS patients with high-resoluti...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2008.10.012
更新日期:2009-02-01 00:00:00
abstract:OBJECTIVE:The advantage of recipient hematopoiesis over that of xenogeneic donors poses a fundamental obstacle to the induction of xenograft tolerance through mixed hematopoietic chimerism. Here we explore the role of beta1 integrins in maintenance of human vs porcine hematopoiesis within a human hematopoietic environm...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2004.11.011
更新日期:2005-03-01 00:00:00
abstract::Two types of murine marrow adherent cells derived from Dexter cultures have been characterized. Exposure of C57B1/6J, ICR, or BDF1 mice to 1000 R x-ray 24 h prior to killing and establishment of liquid marrow cultures resulted in the growth of two types of adherent cells. A macrophage-like cell was phagocytic, nonspec...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1984-08-01 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::Exosomes are virus-size membrane-bound vesicles of endocytic origin present in all body fluids. Plasma of AML patients is significantly enriched in exosomes, which carry a cargo of immunosuppressive molecules and deliver them to recipient immune cells, suppressing their functions. However, whether these exosomes origi...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2019.07.005
更新日期:2019-08-01 00:00:00
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journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1987-08-01 00:00:00
abstract::When cultured mast cells of (WB X C57BL/6)F1-+/+(WBB6F1-+/+) and WB-+/+(WB) mice were directly injected into the skin of genetically mast cell-deficient WBB6F1-W/Wv mice, mast cell clusters appeared at the injection sites. Although in vitro colony-forming ability is comparable between cultured mast cells of WB mice an...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1988-12-01 00:00:00
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pub_type: 临床试验,杂志文章
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更新日期:2008-04-01 00:00:00
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journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1981-05-01 00:00:00
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pub_type: 杂志文章,评审
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更新日期:2017-08-01 00:00:00
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pub_type: 杂志文章,评审
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更新日期:2015-08-01 00:00:00
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journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(00)00620-2
更新日期:2001-01-01 00:00:00
abstract::T(4;11) MLL-AF4 acute leukemia is one of the most aggressive malignancies in infant and pediatric populations. Epidemiological and functional studies have highlighted the influence of an overstimulation of the immune system on leukemia development. This study aimed at assessing if the cell-of-origin of t(4;11) MLL-AF4...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2019.07.004
更新日期:2019-08-01 00:00:00
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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
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journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1990-10-01 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
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更新日期:2003-06-01 00:00:00
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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::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::Transfusion with 10,000 or 20,000 marrow cells resulted in 30+ days survival of 15%-50% of mice exposed to an Ld90 or LD100 or radiation. The use of congenic mice with alloenzyme markers permitted the identification of host and donor cells in the peripheral blood of transfused animals. Donor cells were present initial...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1988-08-01 00:00:00