Background And Objectives: The presence of circulating hematopoietic progenitor cells in patients with myeloproliferative diseases (MPD) has been described. However, the exact nature of such progenitor cells has not been specified until now. The aim of this work was to investigate the presence of endothelial precursor cells in the blood of patients with MPD and to assess the role of the endothelial cell lineage in the pathophysiology of this disease.
Design And Methods: Endothelial progenitor cell marker expression (CD34, prominin (CD133), kinase insert domain receptor (KDR) or vascular endothelial growth factor receptor 2 (VEGFR2), and von Willebrand factor) was assessed in the blood of 53 patients with MPD by quantitative polymerase chain reaction. Clonogenic stem cell assays were performed with progenitor cells and monocytes to assess differentiation towards the endothelial cell lineage. The patients' were divided according to whether they had essential thrombocythemia (ET, n=17), polycythemia vera (PV, n=21) or chronic idiopathic myelofibrosis (CIMF, n=15) and their data compared with data from normal controls (n=16) and patients with secondary thrombo- or erythrocytosis (n=17).
Results: Trafficking of CD34-positive cells was increased above the physiological level in 4/17 patients with ET, 5/21 patients with PV and 13/15 patients with CIMF. A subset of patients with CIMF co-expressed the markers CD34, prominin (CD133) and KDR, suggesting the presence of endothelial precursors among the circulating progenitor cells. Clonogenic stem cell assays confirmed differentiation towards both the hematopoietic and the endothelial cell lineage in 5/10 patients with CIMF. Furthermore, the molecular markers trisomy 8 and JAK2 V617F were found in the grown endothelial cells of patients positive for trisomy 8 or JAK2 V617F in the peripheral blood, confirming the common clonal origin of both hematopoietic and endothelial cell lineages.
Interpretation And Conclusions: Endothelial precursor cells are increased in the blood of a subset of patients with CIMF, and peripheral endothelial cells bear the same molecular markers as hematopoietic cells, suggesting a primary role of pathological endothelial cells in this disease.
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Neoplasma
December 2024
Department of Pathology and Forensic Medicine, College of Basic Medical Sciences, Dalian Medical University, Dalian, China.
MTHFD2 is highly overexpressed in breast cancer tissues, indicating that it might be used as a target in breast cancer treatment. This study aims to determine the role of MTHFD2 in breast cancer cell proliferation and the molecular pathways involved. In order to investigate MTHFD2 gene expression and its downstream pathways in breast cancer, we started our inquiry with a bioinformatics analysis.
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Department of Clinical Pharmacy, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan.
Reproducing intestinal cells in vitro is important in pharmaceutical research and drug development. Caco-2 cells and human iPS cell-derived intestinal epithelial cells are widely used, but few evaluation systems can mimic the complex crypt-villus-like structure. We attempted to generate intestinal cells mimicking the three-dimensional structure from human iPS cells.
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Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada.
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Department of Engineering for Innovation Medicine, Section of Innovation Biomedicine, Hematology Area, University of Verona, Verona, Italy.
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School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, 2199 Lishui Rd, Nanshan, Shenzhen, Guangdong Province 518055, China.
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