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Hematopoietic stem cell

Michał Romański, Jacek Wachowiak, Franciszek K Główka
Treosulfan is a prodrug that undergoes a highly pH- and temperature-dependent nonenzymatic conversion to the monoepoxide {(2S,3S)-1,2-epoxy-3,4-butanediol 4-methanesulfonate [S,S-EBDM]} and diepoxide {(2S,3S)-1,2:3,4-diepoxybutane [S,S-DEB]}. Currently, treosulfan is tested in clinical trials as an alternative to busulfan in conditioning prior to hematopoietic stem cell transplantation (HSCT). Of note, the optimal dosing of the prodrug is still unresolved, especially in infants. In this paper, the pharmacokinetics of treosulfan, together with its biologically active epoxides, is comprehensively reviewed for the first time, with the focus on conditioning prior to HSCT...
March 19, 2018: Clinical Pharmacokinetics
Sinem Civriz Bozdağ, Meltem Kurt Yüksel, Taner Demirer
Stem cells can be either totipotent, pluripotent, multipotent or unipotent. Totipotent cells have the capability to produce all cell types of the developing organism, including both embryonic and extraembryonic tissues. The Hematopoietic Stem Cells (HSC) are the first defined adult stem cells (ASC) that give rise to all blood cells and immune system. Use of HSCs for treatment of hematologic malignancies, which is also called bone marrow (BM) transplantation or peripheral blood stem cells (PBSC) transplantation is the pioneer of cellular therapy and translational research...
March 20, 2018: Advances in Experimental Medicine and Biology
Alison M Condliffe, Anita Chandra
The activated phosphoinositide 3-kinase δ syndrome (APDS), also known as p110δ-activating mutation causing senescent T cells, lymphadenopathy, and immunodeficiency (PASLI), is a combined immunodeficiency syndrome caused by gain-of-function mutations in the phosphoinositide 3-kinase (PI3K) genes PIK3CD (encoding p110δ: APDS1 or PASLI-CD) and PIK3R1 (encoding p85α: APDS2 or PASLI-R1). While the disease is clinically heterogeneous, respiratory symptoms and complications are near universal and often severe...
2018: Frontiers in Immunology
Mariusz Z Ratajczak, Mateusz Adamiak, Monika Plonka, Ahmed Abdel-Latif, Janina Ratajczak
Hematopoietic stem/progenitor cells (HSPCs) circulate in peripheral blood (PB) under normal conditions and their number increases in response to stress, inflammation, tissue/organ injury, and may increase up to 100-fold after administration of mobilization-inducing drugs. Mounting evidence suggests that mobilizing agent-induced mobilization of HSPCs from bone marrow into PB is a result of innate immunity-mediated sterile inflammation in the bone marrow (BM) microenvironment. A critical initiating role in this process is played by tissue/organ injury-mediated or pharmacologically induced release from bone marrow-residing granulocytes and monocytes of (i) danger-associated molecular patterns (DAMPs), (ii) reactive oxygen species (ROS), and (iii) proteolytic and lipolytic enzymes...
March 5, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Tom Verbiest, Rosemary Finnon, Natalie Brown, Lourdes Cruz-Garcia, Paul Finnon, Grainne O'Brien, Eleanor Ross, Simon Bouffler, Cheryl L Scudamore, Christophe Badie
Epidemiological studies have demonstrated an increased leukemia incidence following ionizing radiation exposure, but to date, the target cells and underlying mechanisms of radiation leukemogenesis remain largely unidentified. We engineered a mouse model carrying a different fluorescent marker on each chromosome 2, located inside the minimum deleted region occurring after radiation exposure and recognized as the first leukemogenic event. Using this tailored model, we report that following radiation exposure, more than half of asymptomatic CBA Sfpi1GFP/mCh mice presented with expanding clones of preleukemic hematopoietic cells harboring a hemizygous interstitial deletion of chromosome 2...
March 3, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Wen Hao Neo, Christopher A G Booth, Emanuele Azzoni, Lijun Chi, Paul Delgado-Olguín, Marella F T R de Bruijn, Sten Eirik W Jacobsen, Adam J Mead
Despite the well-established cell-intrinsic role of epigenetic factors in normal and malignant hematopoiesis, their cell-extrinsic role remains largely unexplored. Herein we investigated the hematopoietic impact of inactivating Ezh2 , a key component of polycomb repressive complex 2 (PRC2), in the fetal liver (FL) vascular niche. Hematopoietic specific ( Vav -iCre) Ezh2 -inactivation enhanced FL hematopoietic stem cell (HSC) expansion with normal FL erythropoiesis. In contrast, endothelium ( Tie2 -Cre) targeted Ezh2 -inactivation resulted in embryonic lethality with severe anemia at E13...
March 19, 2018: Blood
Tamara J Somers, Sarah A Kelleher, Caroline S Dorfman, Rebecca A Shelby, Hannah M Fisher, Krista Rowe Nichols, Keith M Sullivan, Nelson J Chao, Gregory P Samsa, Amy P Abernethy, Francis J Keefe
BACKGROUND: Pain is a challenge for patients following hematopoietic stem cell transplantation (HCT). OBJECTIVE: This study aimed to develop and test the feasibility, acceptability, and initial efficacy of a Web-based mobile pain coping skills training (mPCST) protocol designed to address the needs of HCT patients. METHODS: Participants had undergone HCT and reported pain following transplant (N=68). To guide intervention development, qualitative data were collected from focus group participants (n=25) and participants who completed user testing (n=7)...
March 19, 2018: JMIR MHealth and UHealth
V Moalic-Allain
Hematopoietic stem cell transplantation is a common procedure potentially beneficial to many individuals with cancer, hematological, or inherited disorders, and has highlighted the need of related or unrelated donors to perform allograft. Donation of hematopoietic stem cells, either through bone marrow harvest or peripheral blood stem cell collection, is well-established and widespread. Over the past two decades, the peripheral blood stem cell collection by aphaeresis has become the main source of hematopoietic stem cells for transplantation, due to faster engraftment and practicability and lower risk of relapse for high-risk patients...
March 16, 2018: Transfusion Clinique et Biologique: Journal de la Société Française de Transfusion Sanguine
Alfonso Molina, Drew J Winston, Darren Pan, Gary J Schiller
Nocardial infections have been rare after allogeneic hematopoietic stem cell transplantation (HSCT). We report 10 recent cases of late-onset nocardiosis (median time of onset of 508 days after transplantation) primarily in patients on high doses of corticosteroids for graft-versus-host disease (GVHD). All 10 patients had pulmonary infection caused by Nocardia species susceptible to trimethoprim-sulfamethoxazole (TMP-SMX). At time of diagnosis, 8 of 10 patients were not receiving TMP-SMX for prophylaxis of Pneumocystis jiroveci pneumonia (PJP) (7 on atovaquone, 1 on intravenous pentamidine)...
March 16, 2018: Biology of Blood and Marrow Transplantation
Koji Kawamura, Nobuhiro Tsukada, Yoshinobu Kanda, Takashi Ikeda, Akiyo Yoshida, Yasunori Ueda, Tadao Ishida, Kenshi Suzuki, Hirokazu Murakami
Although allogeneic hematopoietic stem cell transplantation (allo-HCT) is considered a potentially curative therapy for patients with multiple myeloma, the role of allo-HCT remains unclear in the novel agent era. We conducted a retrospective study of 65 patients with multiple myeloma who underwent allo-HCT at 19 institutions from 2009 to 2016. Patients received a median of 3 (range 1-7) lines of prior therapy, including at least 1 novel agent, except for autologous HCT. The 3-year progression-free survival (PFS) and overall survival (OS) rates were 18...
March 16, 2018: Biology of Blood and Marrow Transplantation
Mahasweta Gooptu, Haesook T Kim, Vincent T Ho, Edwin P Alyea, John Koreth, Philippe Armand, Jerome Ritz, Sarah Nikiforow, Brett E Glotzbecker, Prashant Nageshwar, Robert J Soiffer, Joseph H Antin, Corey S Cutler
INTRODUCTION: With improvement in transplantation practices in the modern era, non-relapse mortality (NRM) following allogeneic hematopoietic stem cell transplantation (HSCT) has improved, while disease relapse rates have remained unchanged. Survival outcomes are therefore driven by NRM in the modern era. Myeloablative conditioning (MAC) regimens are used to maximize disease control and facilitate engraftment; however their use is often limited by toxicity. The commonly used MAC regimens incorporate either chemotherapy plus total body irradiation (TBI) or combination chemotherapy...
March 16, 2018: Biology of Blood and Marrow Transplantation
Isabelle Bergiers, Tallulah Andrews, Özge Vargel Bölükbaşı, Andreas Buness, Ewa Janosz, Natalia Lopez-Anguita, Kerstin Ganter, Kinga Kosim, Cemre Celen, Gülce Itır Perçin, Paul Collier, Bianka Baying, Vladimir Benes, Martin Hemberg, Christophe Lancrin
Recent advances in single-cell transcriptomics techniques have opened the door to the study of gene regulatory networks (GRNs) at the single-cell level. Here, we studied the GRNs controlling the emergence of hematopoietic stem and progenitor cells from mouse embryonic endothelium using a combination of single-cell transcriptome assays. We found that a heptad of transcription factors (Runx1, Gata2, Tal1, Fli1, Lyl1, Erg and Lmo2) is specifically co-expressed in an intermediate population expressing both endothelial and hematopoietic markers...
March 20, 2018: ELife
Polina Zjablovskaja, Petr Danek, Miroslava Kardosova, Meritxell Alberich-Jorda
Understanding of the hematopoietic stem and progenitor cell biology has important implications for regenerative medicine and the treatment of hematological pathologies. Despite the most relevant data that can be acquired using in vivo models or primary cultures, the low abundance of hematopoietic stem and progenitor cells considerably restricts the pool of suitable techniques for their investigation. Therefore, the use of cell lines allows sufficient production of biological material for the performance of screenings or assays that require large cell numbers...
February 21, 2018: Journal of Visualized Experiments: JoVE
Güldane Cengiz Seval, Pervin Topçuoğlu, Taner Demirer
Hematopoietic stem cell transplantation is an established treatment for patients with a wide range of malignant and nonmalignant conditions. Noninfectious pulmonary complications still remain a leading cause of morbidity and mortality in these patients. Treating hematopoietic stem cell transplantation recipients with noninfectious pulmonary complications is still challenging, and the current treatment armamentarium and strategies are not adequate for patients receiving hematopoietic stem cell transplantation...
March 15, 2018: Balkan Medical Journal
Jiexian Ma, Yingwei Hu, Min Wu, Xiaoqin Wang, Yanhui Xie
Patients who receive a hematopoietic stem cell transplantation (HSCT) exhibit an immune defect after recovering from neutropenia. The current guidelines do not recommend fungal prophylaxis in these patients, except for grades III to IV GVHD in HSCT. Thus, the timing for the initiation and cessation of IFI prophylaxis in immune-compromised patients remains a challenging endeavor. We retrospectively analyzed patients who received auto or allo-HSCT and monitored their immune function after recovering from neutropenia by measuring the levels of IgG, IgA, IgM, as well as the number of T, B, NK cells...
2018: Frontiers in Microbiology
Noriyoshi Yoshinaga, Junya Kanda, Yoshinobu Aisa, Shotaro Hagiwara, Takehiko Mori, Takahiro Fukuda, Yoji Ishida, Hisako Hashimoto, Koji Iwato, Yoshinobu Kanda, Mineo Kurokawa, Hideyuki Nakazawa, Shuichi Ota, Naoyuki Uchida, Tatsuo Ichinohe, Yoshiko Atsuta, Akifumi Takaori-Kondo
PURPOSE: Autologous stem cell transplantation (ASCT) is a treatment option for HIV-positive patients with non-Hodgkin lymphoma (NHL) and multiple myeloma (MM). However, the prognosis after ASCT in HIV-positive Japanese patients remains unclear. The aim of this study was to evaluate the impact of HIV infection on transplant outcomes after ASCT in Japan. PATIENTS AND METHODS: Using the national database of the Japan Society for Hematopoietic Cell Transplantation, we retrospectively evaluated patients with NHL (n= 3,862) and MM (n= 2,670) who underwent their first ASCT between 2001 and 2014...
March 15, 2018: Biology of Blood and Marrow Transplantation
Rajiv K Khajuria, Mathias Munschauer, Jacob C Ulirsch, Claudia Fiorini, Leif S Ludwig, Sean K McFarland, Nour J Abdulhay, Harrison Specht, Hasmik Keshishian, D R Mani, Marko Jovanovic, Steven R Ellis, Charles P Fulco, Jesse M Engreitz, Sabina Schütz, John Lian, Karen W Gripp, Olga K Weinberg, Geraldine S Pinkus, Lee Gehrke, Aviv Regev, Eric S Lander, Hanna T Gazda, Winston Y Lee, Vikram G Panse, Steven A Carr, Vijay G Sankaran
Blood cell formation is classically thought to occur through a hierarchical differentiation process, although recent studies have shown that lineage commitment may occur earlier in hematopoietic stem and progenitor cells (HSPCs). The relevance to human blood diseases and the underlying regulation of these refined models remain poorly understood. By studying a genetic blood disorder, Diamond-Blackfan anemia (DBA), where the majority of mutations affect ribosomal proteins and the erythroid lineage is selectively perturbed, we are able to gain mechanistic insight into how lineage commitment is programmed normally and disrupted in disease...
March 9, 2018: Cell
W P Liu, J F Lu, X Y Chen, Y Xie, Y Q Song, J Zhu, X P Wang
No abstract text is available yet for this article.
January 14, 2018: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
X Chen, J L Wei, Y Huang, E L Jiang, Q L Ma, W H Zhai, Y He, R L Zhang, D L Yang, J F Yao, G X Zhang, S Z Feng, M Z Han
Objective: To compare eficacy and safety of porcine antihuman lymphocyte immunoglobulin (pALG) and rabbit antithymocyte immunoglobulin (rATG) as a part of alternative donor allogeneic hematopoietic stem cell transplantation (AD allo-HSCT) for severe aplastic anemia (SAA). Methods: The clinical data of 46 SAA patients received AD allo-HSCT from January 2006 to November 2016 were retrospectively analyzed. The cohort of patients were divided into two groups based on rATG or pALG as a part of conditioning regimen to compare implantation rate, transplantation related complications and outcome...
January 14, 2018: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
X Ren, T Zhao, J Wang, H H Zhu, H Jiang, J S Jia, S M Yang, B Jiang, D B Wang, X J Huang, Q Jiang
Objective: To explore outcomes in adult with de novo acute myeloid leukemia (AML) received IA10 (10 mg/m(2) d1-3 idarubicin plus cytarabine 100 mg/m(2) d1-7) regimen as induction chemotherapy. Methods: From January 2008 to February 2016, data of consecutive newly-diagnosed AML (non-M(3)) adults treated with IA10 who achieved morphologic leukemia-free state (MLFS) but not accepted allogeneic hematopoietic stem cell transplantation (allo-HSCT) were assessed retrospectively. Results: A total of 198 patients were included in this study with 96 (48...
January 14, 2018: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
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