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Reference
Citation
Sinenko, S.A., Hung, T., Moroz, T., Tran, Q.M., Sidhu, S., Cheney, M.D., Speck, N.A., Banerjee, U. (2010). Genetic manipulation of AML1-ETO-induced expansion of hematopoietic precursors in a Drosophila model.  Blood 116(22): 4612--4620.
FlyBase ID
FBrf0212361
Publication Type
Research paper
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.

PubMed ID
PubMed Central ID
PMC2996118 (PMC) (EuropePMC)
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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Blood
    Title
    Blood
    Publication Year
    1946-
    ISBN/ISSN
    0006-4971
    Data From Reference
    Aberrations (3)
    Alleles (55)
    Genes (41)
    Human Disease Models (1)
    Natural transposons (1)
    Insertions (14)
    Experimental Tools (2)
    Transgenic Constructs (31)