Amlexanox as a possible breakthrough of MLL/AF4-positive acute lymphoblastic

2015 Fiscal Year Final Research Report

• Project/Area Number: 26860740
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Hematology
• Research Institution: Nippon Medical School
• Principal Investigator: TAMAI HAYATO 日本医科大学, 医学部, 講師 (40465349)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: MLL / AF4 / Amlexanox / S100A6 / ALL / leukemia / GVL / P53

Outline of Final Research Achievements

MLL/AF4-positive ALL is associated with a poor prognosis even after allogeneic hematopoietic stem cell transplantation. We have reported that this ALL shows resistance to TNF-α, which is the factor in the GVL effect or tumor immunity, by upregulation of S100A6 expression followed by interference with the p53-caspases pathway. It was reported that Amlexanox, an anti-allergic drug, inhibited translocation pathway of endogenous S100A6 in endothelial cells.The purpose of this study is to examine the effect of Amlexanox on MLL/AF4-positive ALL. We found Amlexanox significantly inhibited S100A6 expression in the presence of TNF-αin MLL/AF4-positive ALL cells. Amlexanox blocked upregulation of S100A6 expression followed by interference with the p53-caspases pathway. In vivo analysis, MLL/AF4-positive transgenic mice fed a diet containing Amlexanox developed significantly less leukemia at the age of 1 year. These findings suggest that Amlexanox may be a breakthrough of MLL/AF4-positive ALL.

Free Research Field

血液内科学