RRC ID 11088
Author Sinenko SA, Hung T, Moroz T, Tran QM, Sidhu S, Cheney MD, Speck NA, Banerjee U.
Title Genetic manipulation of AML1-ETO-induced expansion of hematopoietic precursors in a Drosophila model.
Journal Blood
Abstract Among mutations in human Runx1/AML1 transcription factors, the t(8;21)(q22;q22) genomic translocation that creates an AML1-ETO fusion protein is implicated in etiology of the acute myeloid leukemia. To identify genes and components associated with this oncogene we used Drosophila as a genetic model. Expression of AML1-ETO caused an expansion of hematopoietic precursors in Drosophila, which expressed high levels of reactive oxygen species (ROS). Mutations in functional domains of the fusion protein suppress the proliferative phenotype. In a genetic screen, we found that inactivation of EcRB1 or activation of Foxo and superoxide dismutase-2 (SOD2) suppress the AML1-ETO-induced phenotype by reducing ROS expression in the precursor cells. Our studies indicate that ROS is a signaling factor promoting maintenance of normal as well as the aberrant myeloid precursors and suggests the importance of antioxidant enzymes and their regulators as targets for further study in the context of leukemia.
Volume 116(22)
Pages 4612-20
Published 2010-11-25
DOI 10.1182/blood-2010-03-276998
PII blood-2010-03-276998
PMID 20688956
PMC PMC2996118
MeSH Animals Cell Proliferation Core Binding Factor Alpha 2 Subunit / genetics* Core Binding Factor Alpha 2 Subunit / metabolism* Core Binding Factor beta Subunit / metabolism DNA / metabolism Drosophila / genetics* Drosophila / metabolism Drosophila Proteins / metabolism Forkhead Transcription Factors / metabolism Gene Expression* Gene Expression Regulation Hematopoietic System / cytology Hematopoietic System / metabolism* Hemocytes / cytology* Hemocytes / metabolism Humans Larva / cytology Larva / metabolism Leukemia, Myeloid, Acute / genetics Leukemia, Myeloid, Acute / metabolism Oncogene Proteins, Fusion / genetics* Oncogene Proteins, Fusion / metabolism* Phenotype RUNX1 Translocation Partner 1 Protein Reactive Oxygen Species / metabolism Receptors, Steroid / metabolism Superoxide Dismutase / metabolism
IF 15.132
Times Cited 25
Drosophila 1765R-2 1765R-4 7404R-2 7404R-3 9310R-1 9310R-2 11783R-1 11783R-2