Deciphering the role of GPX4 in acute myeloid leukemia and identification of SMC4 as a possible novel therapeutic target in NPM1-mutated acute myeloid leukemia

Abstract

AML is a form of acute myeloid leukemia with unsatisfactory survival rate. Therefore, novel treatment options are needed. The role of ROS in leukemia and its impact on disease initiation and progression are still unclear. The aim of this thesis was to investigate the role of GPX4, an important ROS scavenger, in leukemia and the possibility to target AML cells by interfering with GPX4 expression. GPX4 was identified as an important factor for survival of healthy hematopoietic and leukemic cells. SMC4 was revealed to be a possible novel therapeutic target in NPM1-mutated AML. Disruption of the MEIS1-SMC4 axis led to prolonged survival in a humanized mouse model and might provide an interesting treatment option in this subtype of acute myeloid leukemia.