Reference Report

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. (Export to RIS)
FlyBase ID	FBrf0212361
Publication Type	Research paper
PubMed ID	20688956
PubMed 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.
DOI	10.1182/blood-2010-03-276998
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Language of Publication	English
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Publication Type	Journal
Abbreviation	Blood
Title	Blood
Publication Year	1946-
ISBN/ISSN	0006-4971
Data from Reference
Aberrations (3)
	Df(3L)fz2 Df(3L)pbl-X1 Df(3L)ZN47
Alleles (55)
	Akt1^GD1361 Akt1^KK100495 Akt1^{Scer\UAS.Exel} Atu^s1938 Avic\GFP^{2x.EGFP.Scer\UAS} Bgb^D Bgb^Scer\UAS.cLa Bro^Scer\UAS.cLa Cat^Scer\UAS.cAa CG5033^EY04217 cpo^BG02810 dsf^MB03062 E2f⁰⁷¹⁷² EcR^{A-ΔC655.F645A.Scer\UAS} EcR^{B2-ΔC655.F645A.Scer\UAS} EcR^{dsRNA.A.Scer\UAS} EcR^KG04522 EcR^NIG.1765R EcR^Q50st foxo^Scer\UAS.cPa fz2^Scer\UAS.N fz^JB hop^Tum Hsap\RUNX1::Hsap\RUNX1T1^{NHR2X.Scer\UAS.cSa} Hsap\RUNX1::Hsap\RUNX1T1^{NHR2Xm7.Scer\UAS.cSa} Hsap\RUNX1::Hsap\RUNX1T1^{NHR3X.Scer\UAS.cSa} Hsap\RUNX1::Hsap\RUNX1T1^{R174Q.Scer\UAS.cSa} Hsap\RUNX1::Hsap\RUNX1T1^Scer\UAS.cSa Hsap\RUNX1::Hsap\RUNX1T1^{YT.Scer\UAS.cSa} Hsap\RUNX1::Hsap\RUNX1T1^{YTR.Scer\UAS.cSa} Hsap\RUNX1^Scer\UAS.cSa Hsap\RUNX1T1^Scer\UAS.cSa Kr² l(2)06496^k14618 lz^Scer\UAS.cSa msl-3¹ msl-3^d01070 Nurf-38^k16102 Nurf-38^NIG.4634R Pkc53E^EY14093 Pten^{dsRNA.Exel.Scer\UAS} Rya-r44F^EY12439 S0279-04^S0279-04 S1364-03^S1364-03 S042938^S042938 Scer\GAL4^Hml.Δ Scer\GAL4^Pxn.PS Sin3A⁰⁸²⁶⁹ Sin3A^GD4387 Sin3A^KK100700 sls^KG00981 Sod2^{dsRNA.Scer\UAS.cKa} Sod2^Scer\UAS.cMa Wnt4^C1 Wnt4^EMS23
Constructs (31)
	P{GD1361} P{GD4387} P{Hml-GAL4.Δ} P{KK100495} P{KK100700} P{lacW} P{NIG.1765R} P{NIG.4634R} P{Pxn-GAL4} P{UAS-2xEGFP} P{UAS-Akt1.Exel} P{UAS-Bgb.L} P{UAS-Bro.L} P{UAS-Cat.A} P{UAS-EcR.A.dsRNA} P{UAS-EcR.A.F645A} P{UAS-EcR.B2.F645A} P{UAS-foxo.P} P{UAS-lz.S} P{UAS-Pten.dsRNA.Exel} P{UAS-RUNX1::RUNX1T1.S} P{UAS-RUNX1.S} P{UAS-RUNX1-RUNX1T1.NHR2X} P{UAS-RUNX1-RUNX1T1.NHR2Xm7} P{UAS-RUNX1-RUNX1T1.NHR3X} P{UAS-RUNX1-RUNX1T1.R174Q} P{UAS-RUNX1-RUNX1T1.YT} P{UAS-RUNX1-RUNX1T1.YTR} P{UAS-RUNX1T1.S} P{UAS-Sod2.dsRNA.K} P{UAS-Sod2.M}
Genes (41)
	Akt1 Atu Avic\GFP Bgb Bro Cat CG5033 cpo dsf E2f EcR Eip78C foxo fz fz2 Hml hop Hsap\RUNX1 Hsap\RUNX1::Hsap\RUNX1T1 Hsap\RUNX1T1 Kr l(2)06496 lz msl-3 ND75 NimC1 Nurf-38 Pkc53E proPO-A1 Pten Pxn Rya-r44F S0279-04 S1364-03 S042938 Scer\GAL4 Sin3A sls Sod2 wg Wnt4
Insertions (14)
	Mi{ET1}dsf^MB03062 P{EPgy2}CG5033^EY04217 P{EPgy2}Rya-r44F^EY12439 P{GT1}cpo^BG02810 P{lacW}l(2)06496^k14618 P{lacW}Nurf-38^k16102 P{lacW}S0279-04^S0279-04 P{lacW}S1364-03^S1364-03 P{lacW}S042938^S042938 P{PZ}E2f⁰⁷¹⁷² P{PZ}Sin3A⁰⁸²⁶⁹ P{SUPor-P}EcR^KG04522 P{SUPor-P}sls^KG00981 P{XP}msl-3^d01070
Natural transposons (1)
	P-element