Arsenic trioxide and all-trans retinoic acid suppress the expression of FLT3-ITD. Issue 11 (18th September 2020)

• Record Type: Journal Article
• Authors: Liang, Cong; Peng, Chun-Jin; Wang, Li-Na; Li, Yu; Zheng, Li-Min; Fan, Zhong; Huang, Dan-Ping; Tang, Wen-Yan; Zhang, Xiao-Li; Huang, Li-Bin; Tang, Yan-Lai; Luo, Xue-Qun
• Is Part Of: Leukemia & lymphoma. Volume 61:Issue 11(2020)
• Page Start: 2692
• Page End: 2699
• Publication Date: 2020-09-18
• Subjects: Degradation -- acute myeloid leukemia -- FLT3-ITD -- all-trans-retinoic acid -- arsenic trioxide; Leukemia -- Periodicals; Lymphomas -- Periodicals; 616.99419
• DOI: 10.1080/10428194.2020.1775212
• Languages: English
• ISSNs: 1042-8194

Abstract

Abstract: The prognosis of patients with acute myeloid leukemia (AML) caused by the FLT3-ITD mutation is poor. Arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) can down-regulate FLT3-ITD level and selectively kill leukemia cells carrying the FLT3-ITD mutation. However, the mechanisms of action of these two compounds are unknown. Here, we found that ATO could bind FLT3-ITD at Lys91 and Asp225, whereas ATRA could bind FLT3-ITD at Lys5 and Gln6. Both compounds could not bind wild-type FLT3. Further studies revealed that ATO/ATRA may suppress the Expression of FLT3-ITD by promoting the UBE2L6-mediated ubiquitination pathway and decreasing the expression of C-MYC. However, further studies are needed to define the mechanisms of these compounds on AML. Our research provides an experimental basis for the use of ATO/ATRA in FLT3-ITD AML in clinical practice.