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Primary myelofibrosis marrow-derived CD14+/CD34- monocytes induce myelofibrosis-like phenotype in immunodeficient mice and give rise to megakaryocytes


Autoři: Taghi Manshouri aff001;  Srdan Verstovsek aff001;  David M. Harris aff001;  Ivo Veletic aff001;  Xiaorui Zhang aff001;  Sean M. Post aff001;  Carlos E. Bueso-Ramos aff002;  Zeev Estrov aff001
Působiště autorů: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, United States of America aff001;  Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States of America aff002
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pone.0222912

Souhrn

To confirm that neoplastic monocyte-derived collagen- and fibronectin-producing fibrocytes induce bone marrow (BM) fibrosis in primary myelofibrosis (PMF), we injected PMF BM-derived fibrocyte-precursor CD14+/CD34- monocytes into the tail vein of NOD-SCID-γ (NSG) mice. PMF BM-derived CD14+/CD34- monocytes engrafted and induced a PMF-like phenotype with splenomegaly, myeloid hyperplasia with clusters of atypical megakaryocytes, persistence of the JAK2V617F mutation, and BM and spleen fibrosis. As control we used normal human BM-derived CD14+/CD34- monocytes. These monocytes also engrafted and gave rise to normal megakaryocytes that, like PMF CD14+/CD34--derived megakaryocytes, expressed HLA-ABC and human CD42b antigens. Using 2 clonogenic assays we confirmed that PMF and normal BM-derived CD14+/CD34- monocytes give rise to megakaryocyte colony-forming cells, suggesting that a subpopulation BM monocytes harbors megakaryocyte progenitor capacity. Taken together, our data suggest that PMF monocytes induce myelofibrosis-like phenotype in immunodeficient mice and that PMF and normal BM-derived CD14+/CD34- monocytes give rise to megakaryocyte progenitor cells.

Klíčová slova:

Spleen – Flow cytometry – Mouse models – Fibroblasts – Fibrosis – Monocytes – Animal sociality – Megakaryocytes


Zdroje

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PLOS One


2019 Číslo 9
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