PEDF reduces malignant cells proliferation and inhibits the progression of myelofibrosis in myeloproliferative neoplasms

• Published in: Biochemical pharmacology 2022-05, Vol.199, p.115013-115013, Article 115013
• Main Authors: Li, Yanjie, Gao, Hui, Dong, Hongyan, Wang, Weiwei, Xu, Zhengqing, Wang, Guozhang, Liu, Yahui, Wang, Haiyang, Ju, Wen, Qiao, Jianlin, Xu, Kailin, Fu, Chunling, Zeng, Lingyu
• Format: Article
• Language: English
• Subjects: Animals; Cell Proliferation; Humans; Malignant cells; Megakaryocytes; Mice; Myelofibrosis; Myeloproliferative Disorders - pathology; Myeloproliferative neoplasms; Neoplasms; PEDF; Primary Myelofibrosis - drug therapy; Primary Myelofibrosis - pathology; TGF-β
• ISSN: 0006-2952; 1873-2968
• DOI: 10.1016/j.bcp.2022.115013

[Display omitted] Pigment epithelial-derived factor (PEDF) exerts a broad spectrum of activities and has been implicated in diverse biological processes and a variety of diseases. However, the role of PEDF in myeloproliferative neoplasms (MPN) remains unknown. In this study, we found that PEDF expression was down-regulated in MPN patients and MPLW515L-transuduced mice. Exogenous PEDF inhibited the peripheral blood cell proliferation in MPLW515L-transuduced mice, reduced tumor cells in bone marrow and spleen, ameliorated hepatosplenomegaly, reduced extramedullary hemopoiesis in the spleen, and prolonged the overall survival of MPN mice. More importantly, PEDF inhibited the progression of myelofibrosis. Moreover, PEDF significantly reduced the proliferation of MPN cells in vitro, especially megakaryocyte-biased HSCs. Furthermore, PEDF induced the apoptosis of MPN cells and reduced the secretion of TGF-β1 in cell culture supernatant. Exogenous PEDF inhibits the proliferation of MPN cells and the progression of myelofibrosis, indicating that it might play an anti-tumor and anti-fibrotic role in MPN. This study implies that PEDF might be a novel agent for the treatment of MPN.