RRC ID |
11088
|
著者 |
Sinenko SA, Hung T, Moroz T, Tran QM, Sidhu S, Cheney MD, Speck NA, Banerjee U.
|
タイトル |
Genetic manipulation of AML1-ETO-induced expansion of hematopoietic precursors in a Drosophila model.
|
ジャーナル |
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.
|
巻・号 |
116(22)
|
ページ |
4612-20
|
公開日 |
2010-11-25
|
DOI |
10.1182/blood-2010-03-276998
|
PII |
S0006-4971(20)31017-X
|
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 |
17.794
|
引用数 |
38
|
WOS 分野
|
HEMATOLOGY
|
リソース情報 |
ショウジョウバエ |
1765R-2
1765R-4
7404R-2
7404R-3
9310R-1
9310R-2
11783R-1
11783R-2 |