دورية أكاديمية
Vitamin K antagonism impairs the bone marrow microenvironment and hematopoiesis.
| العنوان: | Vitamin K antagonism impairs the bone marrow microenvironment and hematopoiesis. |
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| المؤلفون: | Verma D; Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, Frankfurt am Main, Germany., Kumar R; Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, Frankfurt am Main, Germany., Pereira RS; Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, Frankfurt am Main, Germany., Karantanou C; Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, Frankfurt am Main, Germany., Zanetti C; Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, Frankfurt am Main, Germany., Minciacchi VR; Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, Frankfurt am Main, Germany., Fulzele K; Massachusetts General Hospital, Boston, MA., Kunz K; Institute of Biochemistry II, Goethe University, Frankfurt am Main, Germany., Hoelper S; Institute of Biochemistry II, Goethe University, Frankfurt am Main, Germany., Zia-Chahabi S; Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Paris Centre-Cochin, Laboratory of Hematology, Institut Cochin, Université Paris Descartes, Paris, France., Jabagi MJ; Department of Epidemiology of Health Products, French National Agency for Medicines and Health Products Safety, Saint-Denis Cedex, France., Emmerich J; Department of Epidemiology of Health Products, French National Agency for Medicines and Health Products Safety, Saint-Denis Cedex, France.; Vascular Medicine and Cardiology, University Paris Descartes and Hotel Dieu Assistance Publique-Hôpitaux de Paris, Paris, France., Dray-Spira R; Department of Epidemiology of Health Products, French National Agency for Medicines and Health Products Safety, Saint-Denis Cedex, France., Kuhlee F; Institut für Klinische Genetik, Medizinische Fakultät Carl Gustav Carus, Dresden, Germany., Hackmann K; Institut für Klinische Genetik, Medizinische Fakultät Carl Gustav Carus, Dresden, Germany., Schroeck E; Institut für Klinische Genetik, Medizinische Fakultät Carl Gustav Carus, Dresden, Germany., Wenzel P; University Medical Center of the Johannes Gutenberg University, Mainz, Germany., Müller S; Institute of Biochemistry II, Goethe University, Frankfurt am Main, Germany., Filmann N; Institute of Biostatistics and Mathematical Modeling, Goethe University, Frankfurt, Germany., Fontenay M; Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Paris Centre-Cochin, Laboratory of Hematology, Institut Cochin, Université Paris Descartes, Paris, France., Pajevic PD; Boston University Goldman School of Dental Medicine, Boston, MA., Krause DS; Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, Frankfurt am Main, Germany.; German Cancer Consortium, Heidelberg, Germany.; German Cancer Research Center, Heidelberg, Germany; and.; Faculty of Medicine, Johann Wolfgang Goethe University, Frankfurt, Germany. |
| المصدر: | Blood [Blood] 2019 Jul 18; Vol. 134 (3), pp. 227-238. Date of Electronic Publication: 2019 Apr 19. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: United States NLM ID: 7603509 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1528-0020 (Electronic) Linking ISSN: 00064971 NLM ISO Abbreviation: Blood Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2021- : [New York] : Elsevier Original Publication: New York, Grune & Stratton [etc.] |
| مواضيع طبية MeSH: | Bone Marrow Cells/*drug effects , Bone Marrow Cells/*metabolism , Cellular Microenvironment/*drug effects , Hematopoiesis/*drug effects , Vitamin K/*antagonists & inhibitors, Animals ; Anticoagulants/pharmacology ; Biomarkers ; Cell Adhesion Molecules/metabolism ; Dose-Response Relationship, Drug ; Hematopoietic Stem Cells/drug effects ; Hematopoietic Stem Cells/metabolism ; Leukocytes/immunology ; Leukocytes/metabolism ; Macrophages/drug effects ; Macrophages/immunology ; Macrophages/metabolism ; Mice ; Myelodysplastic Syndromes/diagnosis ; Myelodysplastic Syndromes/etiology ; Myelodysplastic Syndromes/metabolism ; Vitamin K/pharmacology ; Warfarin/pharmacology |
| مستخلص: | Vitamin K antagonists (VKAs) have been used in 1% of the world's population for prophylaxis or treatment of thromboembolic events for 64 years. Impairment of osteoblast function and osteoporosis has been described in patients receiving VKAs. Given the involvement of cells of the bone marrow microenvironment (BMM), such as mesenchymal stem cells (MSCs) and macrophages, as well as other factors such as the extracellular matrix for the maintenance of normal hematopoietic stem cells (HSCs), we investigated a possible effect of VKAs on hematopoiesis via the BMM. Using various transplantation and in vitro assays, we show here that VKAs alter parameters of bone physiology and reduce functional HSCs 8-fold. We implicate impairment of the functional, secreted, vitamin K-dependent, γ-carboxylated form of periostin by macrophages and, to a lesser extent, MSCs of the BMM and integrin β3-AKT signaling in HSCs as at least partly causative of this effect, with VKAs not being directly toxic to HSCs. In patients, VKA use associates with modestly reduced leukocyte and monocyte counts, albeit within the normal reference range. VKAs decrease human HSC engraftment in immunosuppressed mice. Following published examples that alteration of the BMM can lead to hematological malignancies in mice, we describe, without providing a causal link, that the odds of VKA use are higher in patients with vs without a diagnosis of myelodysplastic syndrome (MDS). These results demonstrate that VKA treatment impairs HSC function via impairment of the BMM and the periostin/integrin β3 axis, possibly associating with increased MDS risk. (© 2019 by The American Society of Hematology.) |
| التعليقات: | Comment in: Blood. 2021 Aug 5;138(5):417-420. (PMID: 33876243) |
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| معلومات مُعتمدة: | P30 AR066261 United States AR NIAMS NIH HHS |
| المشرفين على المادة: | 0 (Anticoagulants) 0 (Biomarkers) 0 (Cell Adhesion Molecules) 0 (Postn protein, mouse) 12001-79-5 (Vitamin K) 5Q7ZVV76EI (Warfarin) |
| تواريخ الأحداث: | Date Created: 20190421 Date Completed: 20200114 Latest Revision: 20230919 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC7022447 |
| DOI: | 10.1182/blood.2018874214 |
| PMID: | 31003999 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1528-0020 |
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| DOI: | 10.1182/blood.2018874214 |