Arsenic Dispensing Powder Promotes Erythropoiesis in Myelodysplastic Syndromes via Downregulation of HIF1A and Upregulation of GATA Factors

• DOI: 10.1142/s0192415x2150021x
• Publication Date: 2021-03-01T05:51:01Z
• Authors: Teng Fan; Xiaomin Feng; Asumi Yokota; Weiyi Liu; Yuting Tang; Xiaomei Yan; Haiyan Xiao; Yue Wang; Zhongyang Deng; Pan Zhao; Mingjing Wang; Hongzhi Wang; Rou Ma; Xiaomei Hu; Gang Huang
• Keywords: 0303 health sciences; Down-Regulation; Hypoxia-Inducible Factor 1, alpha Subunit; GATA Transcription Factors; Arsenicals; Cell Line; Up-Regulation; 3. Good health; Mice; 03 medical and health sciences; Myelodysplastic Syndromes; Animals; Humans; Erythropoiesis; Powders; Drugs, Chinese Herbal; Retrospective Studies

Traditional Chinese Medicine (TCM) is a practical medicine based on thousands of years of medical practice in China. Arsenic dispensing powder (ADP) has been used as a treatment for MDS patients with a superior efficacy on anemia at Xiyuan Hospital of China Academy of Chinese Medical Sciences. In this study, we retrospectively analyzed MDS patients that received ADP treatment in the past 9 years and confirmed that ADP improves patients’ anemia and prolongs overall survival in intermediate-risk MDS patients. Then, we used the MDS transgenic mice model and cell line to explore the drug mechanism. In normal and MDS cells, ADP does not show cellular toxicity but promotes differentiation. In mouse MDS models, we observed that ADP showed significant efficacy on promoting erythropoiesis. In the BFU-E and CFU-E assays, ADP could promote erythropoiesis not only in normal clones but also in MDS clones. Mechanistically, we found that ADP could downregulate HIF1A in MDS clones through upregulation of VHL, P53 and MDM2, which is involved in two parallel pathways to downregulate HIF1A. We also confirmed that ADP upregulates GATA factors in normal clones. Thus, our clinical and experimental studies indicate that ADP is a promising drug to promote erythropoiesis in both MDS and normal clones with a superior outcome than current regular therapies. ADP promotes erythropoiesis in myelodysplastic syndromes via downregulation of HIF1A and upregulation of GATA factors.