The spontaneous formation of colony-forming units granulocyte/macrophage (CFU-GM) in semisolid cultures has been shown to be due to the endogenous release of cytokines and/or to the hypersensitivity of cells against growth factors. We have reported that increased autonomous CFU-GM growth is an in vitro characteristic of myelofibrosis (MF) which may reflect aberrant hematopoiesis in vivo. Because of its cytokine synthesis-inhibiting action, we speculated that interleukin-10 (IL-10) may inhibit pathological overproduction of myeloid cells in MF by suppression of autonomous myelopoiesis. In this study, IL-10 significantly inhibited autonomous CFU-GM formation in vitro from peripheral blood mononuclear cells (PB MNC) in 10 of 11 patients with MF tested. In all patients, there was a mean inhibition of 69% ranging from 35% to 100%. Suppression of autonomous CFU-GM formation by IL-10 was dose dependent and reversible by the addition of anti-IL-10 antibodies. Our results indicate that IL-10 is a potentially useful molecule to affect aberrant myelopoiesis in patients with MF.
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http://dx.doi.org/10.1111/ejh.12486 | DOI Listing |
J Immunol
July 2023
Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, College of Life Sciences, Beijing Normal University, Beijing, China.
The mechanism of the development of granulocyte progenitor cells into neutrophils under steady-state and pathological conditions remains unclear. In this study, our results showed that with the development of neutrophils from hematopoietic stem cells to mature neutrophils, the expression level of the Hippo kinase MST1 gradually increased. Mst1-specific deficiency in myeloid cells caused neutrophilia, with an expanded granulocytic compartment resulting from a cell-autonomous increase in the number of granulocyte-macrophage progenitors under steady-state conditions and during Listeria monocytogenes infection.
View Article and Find Full Text PDFJ Immunol
March 2022
Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, College of Life Sciences, Beijing Normal University, Beijing, China;
Protein tyrosine phosphatase (PTPase) is critically involved in the regulation of hematopoietic stem cell development and differentiation. Roles of novel isolated receptor PTPase PTPRO from bone marrow hematopoietic stem cells in granulopoiesis have not been investigated. PTPRO expression is correlated with granulocytic differentiation, and mice developed neutrophilia, with an expanded granulocytic compartment resulting from a cell-autonomous increase in the number of granulocyte progenitors under steady-state and potentiated innate immune responses against infection.
View Article and Find Full Text PDFCell Oncol (Dordr)
October 2021
Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes, 1524, CEP 05508-900, São Paulo, SP, Brazil.
Purpose: Despite great advances that have been made in the understanding of the molecular complexity of acute myeloid leukemia (AML), very little has been translated into new therapies. Here, we set out to investigate the impact of cytoskeleton regulatory genes on clinical outcomes and their potential as therapeutic targets in AML.
Methods: Gene expression and clinical data were retrieved from The Cancer Genome Atlas (TCGA) AML study and used for survival and functional genomics analyses.
PLoS Genet
June 2021
Mater Research Institute-University of Queensland, Translational Research Institute, Woolloongabba, Brisbane, Qld, Australia.
Homozygous mutation of the Csf1r locus (Csf1rko) in mice, rats and humans leads to multiple postnatal developmental abnormalities. To enable analysis of the mechanisms underlying the phenotypic impacts of Csf1r mutation, we bred a rat Csf1rko allele to the inbred dark agouti (DA) genetic background and to a Csf1r-mApple reporter transgene. The Csf1rko led to almost complete loss of embryonic macrophages and ablation of most adult tissue macrophage populations.
View Article and Find Full Text PDFSci Total Environ
September 2021
Cancer Biology Lab, Centre for Molecular and Nanomedical Sciences, Centre for Nanoscience and Nanotechnology, School of Bio and Chemical Engineering, Sathyabama Institute of Science and Technology, Chennai 600119, Tamil Nadu, India. Electronic address:
Experimental evidence from the etiology of cancer studies suggests that a correlation between Bisphenol-A (BPA) exposure and alterations in hematopoiesis leads to blood cancer. In our study zebrafish were used to assess the lethality, developmental effect, embryonic apoptosis and changes in transcription factor of hematopoiesis through EGFR/ERK signaling pathways in response to BPA. The in silico interaction of EGFR and BPA was analysed by molecular dynamic simulation.
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