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Hematopoietic stem cell

Anne Bouvier, Bénédicte Ribourtout, Sylvie François, Corentin Orvain, Damien Luque Paz, Annaëlle Beucher, Alexandre Guérard, Philippe Guardiola, Valérie Ugo, Odile Blanchet, Franck Geneviève, Aline Schmidt, Mathilde Hunault-Berger
Allogeneic hematopoietic stem cell transplantation (HSCT) is the one of treatment known to cure acute myeloid leukemia (AML). Relapse of AML remains the major cause of treatment failure in patients after HSCT. In rare cases, secondary leukemia is derived from donor cells, designated as donor cell leukemia (DCL) This article is protected by copyright. All rights reserved.
July 14, 2018: European Journal of Haematology
Kyo Izumida, Atsushi Kaneko, Kazuya Takahashi, Shigeru Kusumoto, Tomoko Narita, Akiyoshi Takami, Shinsuke Iida, Katsumi Aoyagi, Yasuhito Tanaka
AIM: Recently, the measurement of hepatitis B surface antigen and anti-hepatitis B core antigen (HBcAb) and/or anti-hepatitis B surface antigen is recommended before various therapies to identify the patients at risk of HBV reactivation. However, a recent study reported that HBV reactivation occurred in HBcAb negative patients, indicating that it is challenging to identify patients with a history of HBV infection using conventional HBcAb reagent. We developed a highly sensitive HBcAb (HBcAb-HS) assay for reducing of the HBV reactivation risk...
July 13, 2018: Hepatology Research: the Official Journal of the Japan Society of Hepatology
Peter Valent, Emir Hadzijusufovic, Thomas Grunt, Heidrun Karlic, Barbara Peter, Harald Herrmann, Gregor Eisenwort, Gregor Hoermann, Axel Schulenburg, Michael Willmann, Rainer Hubmann, Medhat Shehata, Edgar Selzer, Karoline V Gleixner, Thomas Rülicke, Wolfgang R Sperr, Brigitte Marian, Michael Pfeilstöcker, Hubert Pehamberger, Felix Keil, Ulrich Jäger, Christoph Zielinski
In 2008 the Ludwig Boltzmann Cluster Oncology (LBC ONC) was established on the basis of two previous Ludwig Boltzmann Institutes working in the field of hematology and cancer research. The general aim of the LBC ONC is to improve treatment of hematopoietic neoplasms by eradicating cancer-initiating and disease-propagating cells, also known as leukemic stem cells (LSC) in the context of leukemia. In a first phase, the LBC ONC characterized the phenotype and molecular aberration profiles of LSC in various malignancies...
July 13, 2018: Wiener Klinische Wochenschrift
Takao Ohta, Cornelia Monzel, Alexandra S Becker, Anthony D Ho, Motomu Tanaka
We studied the dynamic behavior of human hematopoietic stem cells (HSC) on the in vitro model of bone marrow surfaces in the absence and presence of chemokine (SDF1α). The deformation and migration of cells were investigated by varying the chemokine concentration and surface density of ligand molecules. Since HSC used in this study were primary cells extracted from the human umbilical cord blood, it is not possible to introduce molecular reporter systems before or during the live cell imaging. To account for the experimental observations, we propose a simple and general theoretical model for cell crawling...
July 13, 2018: Scientific Reports
Linjia Jiang, Xue Han, Jin Wang, Chen Wang, Xiaoqiang Sun, Jiayi Xie, Guojin Wu, Hiep Phan, Zhenguo Liu, Edward T H Yeh, ChengCheng Zhang, Meng Zhao, Xunlei Kang
No abstract text is available yet for this article.
July 13, 2018: Journal of Experimental Medicine
M Kyle Cromer, Sriram Vaidyanathan, Daniel E Ryan, Bo Curry, Anne Bergstrom Lucas, Joab Camarena, Milan Kaushik, Sarah R Hay, Renata M Martin, Israel Steinfeld, Rasmus O Bak, Daniel P Dever, Ayal Hendel, Laurakay Bruhn, Matthew H Porteus
Genome-editing technologies are currently being translated to the clinic. However, cellular effects of the editing machinery have yet to be fully elucidated. Here, we performed global microarray-based gene expression measurements on human CD34+ hematopoietic stem and progenitor cells that underwent editing. We probed effects of the entire editing process as well as each component individually, including electroporation, Cas9 (mRNA or protein) with chemically modified sgRNA, and AAV6 transduction. We identified differentially expressed genes relative to control treatments, which displayed enrichment for particular biological processes...
July 10, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
Yu Zhang, Chi Hua Sarah Lin, Kenneth Kaushansky, Huichun Zhan
The myeloproliferative neoplasms (MPNs) are stem cell disorders characterized by hematopoietic stem/progenitor cell (HSPC) expansion and overproduction of mature blood cells. The acquired kinase mutation JAK2V617F plays a central role in these disorders. The mechanisms responsible for HSPC expansion in MPNs are not fully understood, limiting the effectiveness of current treatments. One hallmark feature of the marrow in patients with MPNs is megakaryocyte (MK) hyperplasia. Previously, we reported that JAK2V617F-bearing MKs cause a murine myeloproliferative syndrome with HSPC expansion...
July 13, 2018: Stem Cells
Farnaz Foolad, Samuel L Aitken, Roy F Chemaly
Allogeneic hematopoietic cell transplants (allo-HCT) recipients are at high-risk of reactivation of cytomegalovirus (CMV), and reactivation is associated with significant morbidity and mortality. Although available anti-CMV therapies may be effective for prevention of CMV, they are plagued by unacceptable toxicities that prohibit their use in the post-transplant period. Recently studied CMV-active agents, such as maribavir and brincidofovir, failed to reduce the incidence of CMV infection in HCT recipients...
July 13, 2018: Expert Review of Clinical Pharmacology
Yiming Huang, Hong Xu, Thomas Miller, Yujie Wen, Suzanne T Ildstad
Facilitating cells (FC) are a CD8+ TCR- bone marrow subpopulation that enhance engraftment of purified hematopoietic stem cells (HSC) and induce antigen-specific CD4+ CD25+ FoxP3+ regulatory T cells (Treg) in vivo. The major subpopulation in FC resembles plasmacytoid precursor dendritic cells (p-preDC) both phenotypically and functionally. Here, we report that the number of FC was significantly reduced in Flt3 ligand knockout (Flt3-L-KO) mice. Specifically, there was a selective decrease in the B220+ CD11c+ CD11b- p-preDC FC subpopulation...
July 13, 2018: Stem Cells
Aditi Bapat, Nakia Keita, William Martelly, Paul Kang, Christopher Seet, Jeffery R Jacobsen, Peter Stoilov, Chengcheng Hu, Gay M Crooks, Shalini Sharma
Myeloid malignancies including myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myeloid leukemia are characterized by abnormal proliferation and differentiation of hematopoietic stem and progenitor cells (HSPCs). Reports on analysis of bone marrow samples from patients have revealed a high incidence of mutations in splicing factors in early stem and progenitor cell clones, but the mechanisms underlying transformation of HSPCs harboring these mutations remain unknown. Using ex vivo cultures of primary human CD34+ cells as a model, we find that mutations in splicing factors SRSF2 and U2AF1 exert distinct effects on proliferation and differentiation of HSPCs...
July 13, 2018: Stem Cells
Seon-Yeong Jeong, Jin-A Kim, Il-Hoan Oh
Accumulating studies have shown the cellular nature of hematopoietic stem cell (HSC) niche in bone marrow (BM) and their degenerative changes under leukemic conditions. However, the dynamic adaptation of niche cells to changes in physiological stimulatory signals remains largely uncharacterized. Here, we have established a niche stimulation model induced by 5-fluorouracil. This model reveals a rapid and reversible conversion of mesenchymal cells into niche-like stromal cells, which exhibit a platelet derived growth factor receptor-alpha+ /leptin receptor+ (PL) phenotype...
July 13, 2018: Stem Cells
In-Cheol Baek, Eun-Jeong Choi, Dong-Hwan Shin, Hyoung-Jae Kim, Tai-Gyu Kim
HLA-B*46:67 differs from HLA-B*46:01:01 in codons 94, 95 and 103 in exon 3. This article is protected by copyright. All rights reserved.
July 12, 2018: HLA
Shohei Yamamoto, Daisuke Toyama, Yumiko Sugishita, Ryota Kaneko, Naoko Okamoto, Masaya Koganesawa, Sachio Fujita, Kosuke Akiyama, Ryosuke Matsuno, Keiichi Isoyama
Hepatic SOS is a potentially life-threatening complication of conditioning for allogeneic HSCT. rTM is a new drug for treating DIC. We report our experience of the use of rTM as a prophylaxis against SOS in high-risk pediatric patients that underwent HSCT. We evaluated the cases of 19 pediatric hematology and oncology patients who underwent HSCT at our institution between 2007 and 2016. The patients who received HSCT after 2012 (n = 8) were treated with rTM as a prophylaxis against SOS together with UDCA and LMWH, whereas the others (n = 11) were only treated with UDCA and LMWH...
July 12, 2018: Pediatric Transplantation
Giuseppe Leone, Livio Pagano
Infections remain a significant problem in myelodysplastic syndromes (MDS) in treated as well in non-treated patients and assume a particular complexity. The susceptibility to infections is due, in the absence of intensive chemotherapies, mainly to functional defects in the myeloid lineage with or without neutropenia. Furthermore, MDS includes a heterogeneous group of patients with very different prognosis, therapy and risk factors regarding survival and infections. You should distinguish risk factors related to the disease, like as neutrophils function impairment, neutropenia, unfavorable cytogenetics and bone marrow insufficiency; factors related to the patient, like as age and comorbidities, and factors related to the therapy...
2018: Mediterranean Journal of Hematology and Infectious Diseases
Xiao-Fang Wei, You-Fan Feng, Qiao-Lin Chen, Qi-Ke Zhang
Background: As a disease of hematopoietic stem cell, chronic myeloid leukemia (CML) possesses unique biological and clinical features. However, the biologic mechanism underlying its development remains poorly understood. Thus, the objective of the present study is to discuss the effect of cytidine deaminase (CDA) gene silencing on the apoptosis and proliferation of CML K562 cells. Methods: CDA mRNA expression was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and enzymatic activity of CDA was measured by a nuclide liquid scintillation method...
2018: Cancer Cell International
Henning Hintzsche, Gracia Montag, Helga Stopper
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
July 13, 2018: Scientific Reports
Michael K Strasser, Philipp S Hoppe, Dirk Loeffler, Konstantinos D Kokkaliaris, Timm Schroeder, Fabian J Theis, Carsten Marr
Molecular regulation of cell fate decisions underlies health and disease. To identify molecules that are active or regulated during a decision, and not before or after, the decision time point is crucial. However, cell fate markers are usually delayed and the time of decision therefore unknown. Fortunately, dividing cells induce temporal correlations in their progeny, which allow for retrospective inference of the decision time point. We present a computational method to infer decision time points from correlated marker signals in genealogies and apply it to differentiating hematopoietic stem cells...
July 12, 2018: Nature Communications
Amelie V Guitart, Andrew J Finch, Kamil R Kranc
In this issue of JEM , Umemoto et al. ( demonstrate that calcium influx stimulates mitochondrial metabolism and initiates proliferation in hematopoietic stem cells (HSCs). Extracellular adenosine, sourced from surrounding hematopoietic progenitors, inhibits this calcium influx, thereby suppressing mitochondrial metabolism and promoting HSC quiescence. This is the first demonstration that a calcium-mitochondria pathway regulates HSC division.
July 12, 2018: Journal of Experimental Medicine
Laura Alonso, Marta González-Vicent, Cristina Belendez, Isabel Badell, Ana Sastre, Antonia Rodríguez-Villa, Mar Bermúdez-Cortés, Raquel Hladun, Cristina Díaz de Heredia
BACKGROUND AND OBJECTIVES: A recently occurring increase of the prevalence of haemoglobinopathies, β-thalassaemia major (TM) and sickle cell disease (SCD) over the last two decades in our country has generated new needs in terms of medical resources for both prevention and treatment of these patients. Allogeneic haematopoietic stem cell transplant (allo-HSCT) is a curative treatment available for patients who have severe haemoglobinopathies. The main objective of this study was to evaluate the results of allo-HSCT in paediatric patients with TM or SCD performed in paediatric hematopoietic transplant units within the Spanish Group of Bone Marrow Transplantation in Children (GETMON)...
July 9, 2018: Medicina Clínica
Guohui Sun, Lijiao Zhao, Rugang Zhong, Yongzhen Peng
The DNA repair protein, O6 -methylguanine DNA methyltransferase (MGMT), can confer resistance to guanine O6 -alkylating agents. Therefore, inhibition of resistant MGMT protein is a practical approach to increase the anticancer effects of such alkylating agents. Numerous small molecule inhibitors were synthesized and exhibited potential MGMT inhibitory activities. Although they were nontoxic alone, they also inhibited MGMT in normal tissues, thereby enhancing the side effects of chemotherapy. Therefore, strategies for tumor-specific MGMT inhibition have been proposed, including local drug delivery and tumor-activated prodrugs...
July 13, 2018: Future Medicinal Chemistry
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