Abstract：
:Familial platelet disorder with propensity to acute myeloid leukemia (FPD/AML) is an autosomal dominant disease associated with a germline mutation in the RUNX1 gene and is characterized by thrombocytopenia and an increased risk of developing myeloid malignancies. We generated induced pluripotent stem cells (iPSCs) from dermal fibroblasts of a patient with FPD/AML possessing a nonsense mutation R174X in the RUNX1 gene. Consistent with the clinical characteristics of the disease, FPD iPSC-derived hematopoietic progenitor cells were significantly impaired in undergoing megakaryocytic differentiation and subsequent maturation, as determined by colony-forming cell assay and surface marker analysis. Notably, when we corrected the RUNX1 mutation using transcription activator-like effector nucleases in conjunction with a donor plasmid containing normal RUNX1 cDNA sequences, megakaryopoiesis and subsequent maturation were restored in FPD iPSC-derived hematopoietic cells. These findings clearly indicate that the RUNX1 mutation is robustly associated with thrombocytopenia in patients with FPD/AML, and transcription activator-like effector nuclease-mediated gene correction in iPSCs generated from patient-derived cells could provide a promising clinical application for treatment of the disease.
journal_name
Exp Hematoljournal_title
Experimental hematologyauthors
Iizuka H,Kagoya Y,Kataoka K,Yoshimi A,Miyauchi M,Taoka K,Kumano K,Yamamoto T,Hotta A,Arai S,Kurokawa Mdoi
10.1016/j.exphem.2015.05.004subject
Has Abstractpub_date
2015-10-01 00:00:00pages
849-57issue
10eissn
0301-472Xissn
1873-2399pii
S0301-472X(15)00170-8journal_volume
43pub_type
杂志文章abstract：:As a result of the introduction of new sequencing technologies, the molecular landscape of acute myeloid leukemia (AML) is rapidly evolving. From karyotyping, which detects only large genomic aberrations of metaphase chromosomes, we have moved into an era when sequencing of each base pair allows us to define the AML g...
journal_title：Experimental hematology
pub_type： 杂志文章,评审
doi：10.1016/j.exphem.2015.05.009
更新日期：2015-08-01 00:00:00
abstract：OBJECTIVE:Potent immunosuppressants, such as rapamycin, FK506, and ascomycin, are known to regulate the phosphorylation of proteins. The purpose of this study was to investigate the effects of these immunosuppressants on differentiation of several human myeloid leukemic cell lines. MATERIALS AND METHODS:Human myeloid ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(01)00626-9
更新日期：2001-05-01 00:00:00
abstract：:The renal tumor RCC-3-JCK, when transplanted into immunodeficient mice, caused an erythrocytic polycythemia. When grown in culture, the tumor cells secreted a substance into the culture medium that chromatographed by size-exclusion high-performance liquid chromatography similarly to purified human erythropoietin (Ep) ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1985-01-01 00:00:00
abstract：:Growth and differentiation of hematopoietic stem cells occur in close contact with the cells and extracellular-matrix (ECM) proteins of the hematopoietic microenvironment. We observed the role of fibronectin, a matrix glycoprotein proposed to be involved in the attachment of hematopoietic cells and in the binding of s...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1994-12-01 00:00:00
abstract：:The cloning efficiency of T-lymphocyte progenitor cells (CFU-T) is dependent on mononuclear cell concentration, with a triphasic growth curve. At low plating cell concentrations, hydrocortisone causes a dose-dependent decrease in cloning efficiency, whereas at high cell concentrations hydrocortisone causes increased c...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1989-02-01 00:00:00
abstract：:The immediate hematopoietic response to 3'-azido-3'-deoxythymidine (AZT) was characterized in an unperturbed and regenerating mouse marrow model to identify the in vivo hematopoietic targets of AZT and test whether AZT toxicity is dependent on the proliferative activity of the hematopoietic targets. B6D2F1 mice receiv...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1994-01-01 00:00:00
abstract：:Distinctive patterns of chromatin modification control gene expression and define cellular identity during development and cell differentiation. Polycomb repressive complex 2 (PRC2), the sole mammalian enzymatic complex capable of establishing gene-repressive high-degree methylation of histone H3 at lysine 27 (H3K27),...
journal_title：Experimental hematology
pub_type： 杂志文章,评审
doi：10.1016/j.exphem.2015.05.001
更新日期：2015-08-01 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
abstract：:G-banded metaphase chromosomes prepared from 14 male CBA/Ca mice with histologically confirmed myeloid leukemia (ML) were studied in an effort to identify specific chromosomal changes associated with radiation leukemogenesis. The chromosome studies were undertaken as part of a larger investigation of radiation carcino...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1993-03-01 00:00:00
abstract：:Mast cell (MC)-fibroblast-immunocompetent cell interactions may play a role in the inflammatory and fibrotic processes present in chronic graft-vs.-host disease (cGVHD). Interactions between these cell types were examined in both murine and human cGVHD models. To this purpose, cell supernatants from mice or humans wit...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1997-03-01 00:00:00
abstract：OBJECTIVE:The Hedgehog family of intercellular proteins has a crucial role in embryonic development. Recent experimental data suggests that the Hedgehog pathway may play a role in early hematopoiesis and angiogenesis. Stem cell leukemia (SCL), a basic helix-loop-helix (bHLH) transcription factor, is essential for the s...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2006.07.019
更新日期：2006-12-01 00:00:00
abstract：OBJECTIVE:To assess the contribution of bone marrow (BM)-derived endothelial progenitor cells (EPCs) to the neovascularisation of cutaneous incisional wounds. METHODS:Lethally irradiated C57Bl/6 mice were transplanted with BM mononuclear cells from Tie2/lacZ mice, which constitutively overexpressed beta-galactosidase ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2006.10.016
更新日期：2007-03-01 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：:A cell line (LAMA-84) has been established from the blood of a patient with chronic myeloid leukemia in acute phase. LAMA-84 cells retained the patient's chromosome abnormalities, i.e., triplication of all chromosomes except chromosome 18, the presence of Philadelphia (Ph) chromosome in 4-5 copies, and the presence of...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1987-09-01 00:00:00
abstract：:Retroviral gene marking has been used successfully in preclinical and clinical transplantation settings. Highly sensitive techniques for vector insertion-site determination, such as linear amplification-mediated polymerase chain reaction (LAM-PCR) in conjunction with next-generation sequencing, have been introduced to...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2012.09.003
更新日期：2013-01-01 00:00:00
abstract：:Details are given of response and toxicity after high dose chemotherapy followed by autologous bone marrow infusion. High dose nitrosurea therapy (600-1000 mg/m2 BCNU) was predominantly associated with hematopoietic toxicity but recovery was within 4-5 weeks after BCNU therapy. High dose combination chemotherapy using...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1979-01-01 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：OBJECTIVE:The retinoic acid receptors (RARs) alpha, beta2, and gamma regulate specific subsets of target genes during all-trans retinoic acid (RA) induced differentiation of F9 teratocarcinoma stem cells. The Tie1 gene exhibited reduced expression in RA-treated F9 RARgamma-/- cells as compared to wild-type (WT) by micr...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2007.12.016
更新日期：2008-05-01 00:00:00
abstract：:Patients subjected to prolonged exposure to nitrous oxide (N2O) often develop megaloblastic bone marrow changes. This toxicity is due to the N2O-mediated inactivation of cobalamin-dependent enzymes with resultant perturbations in cell metabolism. The effect of N2O on the behavior of murine colony-forming units-cytokin...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1993-02-01 00:00:00
abstract：OBJECTIVE:Umbilical cord blood (CB) provides an alternative source of hematopoietic progenitor cells for transplantation; however, prolonged thrombocytopenia remains a major obstacle due to the low numbers of megakaryocyte progenitor (Mk-prog) cells and their subsequent delayed engraftment. In this study, we improved t...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(02)00884-6
更新日期：2002-09-01 00:00:00
abstract：:Benign constitutional neutropenia (BCN) is an asymptomatic condition characterized by mild chronic neutropenia in patients with no history of recurrent infections. Most patients are referred for further testing, increasing health care costs. We present an alternative form of assessment of individuals with BCN based on...
journal_title：Experimental hematology
pub_type： 临床试验,杂志文章
doi：10.1016/j.exphem.2018.10.007
更新日期：2019-01-01 00:00:00
abstract：:Pathogenesis of cytomegalovirus (CMV)-induced myelosuppression is not clearly understood and could be related to a direct toxic effect on the marrow progenitors and/or an alteration of the marrow environment. Myeloid progenitors (granulocyte-macrophage colony-forming units, CFU-GM) were not affected by incubation with...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1991-02-01 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：OBJECTIVE:Tumor-associated antigens (TAA) are the basis for antigen-specific immunotherapy. The human homolog of the murine double-minute 2 oncoprotein (MDM2) is a putative TAA because it is overexpressed in several malignancies, including chronic lymphocytic leukemia (CLL) cells compared with normal B lymphocytes. PA...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2005.09.016
更新日期：2006-01-01 00:00:00
abstract：:Cancer stem cells (CSCs), including leukemia stem cells (LSCs), exhibit self-renewal capacity and differentiation potential and have the capacity to maintain or renew and propagate a tumor/leukemia. The initial isolation of CSCs/LSCs was in adult myelogenous leukemia, although more recently, the existence of CSCs in a...
journal_title：Experimental hematology
pub_type： 杂志文章,评审
doi：10.1016/j.exphem.2017.04.010
更新日期：2017-08-01 00:00:00
abstract：:The influence of erythrocytes, extracts of erythrocytes and hemin was assessed on colony formation in vitro by human bone marrow multipotential (CFUGEMM), erythroid (BFUE) and granulocyte-macrophage (CFUGM) progenitor cells. Colony formation by CFUGEMM and BFUE present in the low density (less than 1.077 g/cm3) fracti...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1983-09-01 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：:An improved negative immunomagnetic selection strategy has been devised for the enrichment of primitive hemopoietic cells using the high proliferative potential colony-forming cell (HPP-CFC) assay as an index of stem cell purification. Immunomagnetic selection was carried out using goat anti-rat conjugated M-450 Dynab...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1991-02-01 00:00:00
abstract：:In vitro studies of human hemopoiesis are often limited by the availability of normal bone marrow. We have overcome this difficulty by taking advantage of the bone marrow fragments removed during total hip replacement. We report here a comparative study of the colony forming capacity of trochanter and sternal or iliac...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1979-07-01 00:00:00
abstract：:Ouabain has been shown to increase the number of clonally derived erythroid stem cells, CFUE and BFUE, from normal murine bone marrow. We report here that digoxin and theophylline also enhance erythroid stem cell colony formation, in the presence of suboptimal concentrations of erythropoietin (Ep) (0.01 IU/ml) in meth...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1982-09-01 00:00:00
