Open AccessPrimary myelofibrosis marrow-derived CD14+/CD34- monocytes induce myelofibrosis-like phenotype in immunodeficient mice and give rise to megakaryocytes
Author(s) -
Taghi Manshouri,
Srđan Verstovšek,
David Harris,
Ivo Veletić,
Xiaorui Zhang,
Sean M. Post,
Carlos E. BuesoRamos,
Zeev Estrov
Publication year - 2019
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0222912
Subject(s) - megakaryocyte , myelofibrosis , cd34 , cd14 , progenitor cell , bone marrow , myeloid , biology , immunology , microbiology and biotechnology , cancer research , stem cell , immune system
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 JAK2 V617F 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.