Polymorphonuclear Neutrophil and Megakaryocyte Mutual Involvement in Myelofibrosis Pathogenesis

Unité Inserm U1077, Caen, Lower Normandy, France
Leukemia and Lymphoma (Impact Factor: 2.89). 05/2002; 43(4):719-24. DOI: 10.1080/10428190290016809
Source: PubMed


The study presented here, performed on the bone marrow from patients with idiopathic myelofibrosis (MF) and on a murine model of MF, demonstrates a pathological interaction between PMN leukocytes and megakaryocyte (Mk), correlated with MF development. The data obtained revealed abnormal subcellular P-selectin distribution, which appeared to correlate with excessive and pathological emperipolesis of PMN leukocytes within Mk, leading to the destruction of Mk storage organelles and leakage of alpha-granular contents into the bone marrow microenvironment. The prominent role of growth factors, PDGF and TGFbeta, stored in the Mk alpha-granular compartment in the generation of MF has been previously largely documented. Both growth factors are essential for the Mk-dependent fibroblast proliferation. The destructive mutual cellular interaction of Mk and PMN leading to the pathological release of PDGF and TGFbeta within the bone marrow microenvironment may participate, through fibroblast activation, to the generation of MF. Therefore, this study provides insight into the possible pathophysiological mechanisms for the genesis of MF.

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    • "Candidate factors include the alpha granule contents, plateletderived growth factor (PDGF), platelet factor 4 (PF-4), transforming growth factor b (TGFb), basic fibroblast growth factor (b-FGF) and calmodulin (Le Bousse-Kerdiles & Martyre, 2001). It has also been reported that abnormal subcellular location of P-Selectin within megakaryocytes correlates with emperipoiesis, thence disrupting megakaryocyte organelles and causing leakage of alpha granule contents (Schmitt et al, 2002). Monocytes activated following contact with the extracellular matrix upregulate CD25 expression, and increase production of TGFb and interleukin-1, which have pro-fibrotic potential. "
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