PDGF/PDGFR May be Involved in the Physiopathologic Mechanism of Essential Thrombocythemia

Our previous studies have demonstrated that PDGF (Platelet-derived growth factor) has a potential effect in the regulation of hematopoiesis and megakaryopoiesis (Yang et al, Thromb Haemastasis , 1997; Ye et al, Haematologica, 2010). Essential Thrombocythemia (ET) is characterized by persistently elevated platelet counts in the context of a normal red cell mass. However, the physiopathologic mechanism of ET is still under investigation. Here, we tested the bone marrow plasma levels of PDGF-BB in essential thrombocythemia patients (n=16) and normal control (n=8), and found an increased PDGF-BB levels in ET patients (2070.92±123.98 pg/ml), compared with normal control (1381.85±128.37pg/ml) (P=0.002). Furthermore, we have demonstrated the presence of functional PDGF receptors (PDGFR) in human megakaryocytes, and their ability to mediate a mitogenic response by bone marrow colony-forming unit-megakaryocyte (CFU-MK) formation assay (n=6). PDGF-BB stimulated in vitro megakaryopoiesis via PDGFR. It also showed a direct stimulatory effect of PDGF-BB on c-Fos expressions in megakaryocytic cells, CHRF. We speculate that these transcription factors might be involved in the signal transduction of PDGF on the regulation of megakaryopoiesis. PDGF also enhanced platelet recovery in mice model with radiation-induced thrombocytopenia. Studies showed that PDGF, like thrombopoietin (TPO), significantly promoted platelet recovery and the formation of bone marrow CFU-MK in this irradiated-mouse. An increased number of hematopoietic stem/progenitor cells and a reduction of apoptosis were found in the bone marrow histology sections. We also demonstrated that PDGF activated the p - Akt , p-Jak2 and p-Stat3 expression, while addition of imatinib mesylate reduced p-Akt, p-Jak2 and p-Stat3 expression in CHRF cells. Our findings suggested that the PDGF-initiated megakaryopoiesis is likely to be mediated via PDGF receptors with subsequent activation of the Akt and Jak2/ Stat3 pathways. These studies provide a possible explanation that PDGF/PDGFR may be involved in the physiopathologic mechanism of essential thrombocythemia. Disclosures Yang: National Natural Science Foundation of China(81270580): Research Funding.