Reference Report

Reference
Citation	Muyrers-Chen, I., Rozovskaia, T., Lee, N., Kersey, J.H., Nakamura, T., Canaani, E., Paro, R. (2004). Expression of leukemic MLL fusion proteins in Drosophila affects cell cycle control and chromosome morphology. Oncogene 23(53): 8639--8648. (Export to RIS)
FlyBase ID	FBrf0180611
Publication Type	Research paper
PubMed ID	15378024
PubMed Abstract	The Mixed Lineage Leukemia (MLL) gene is involved in lymphoblastic and myeloid leukemia through chromosome translocations leading to fusion of MLL to partner genes, or through internal MLL rearrangements. MLL is the mammalian counterpart of the Drosophila trithorax (trx) gene, involved in maintaining active gene expression states. We have used transgenic Drosophila to assess the molecular targets and cellular processes affected by MLL and two of its leukemic fusion proteins. We find that whereas expression of normal human MLL in flies does not result in phenotypic alterations, overexpressing the human MLL-AF9 and MLL-AF4 proteins causes larval to pupal lethality, which interestingly resembles the phenotypes displayed by certain Drosophila trx mutant alleles. MLL-AF9 and MLL-AF4 transgenic flies exhibit antagonistic alterations in cell cycle progression. Additionally, flies expressing MLL-AF9 display impairment in higher order chromatin integrity, evidenced in decondensation of mitotic figures. The effects of MLL fusion proteins in Drosophila suggest that alteration of chromatin structure by MLL fusion proteins may contribute to the lethal phenotype. Our results indicate that the mode(s) of action of MLL-AF9 in Drosophila varies from that of MLL-AF4. Taken together, the expression of MLL fusion proteins in Drosophila provides a new and powerful system to reveal and characterize biological activities associated with MLL fusion proteins.
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Language of Publication	English
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Publication Type	Journal
Abbreviation	Oncogene
Title	Oncogene
Publication Year	1987-
ISBN/ISSN	0950-9232
Data from Reference
Alleles (20)
	Hsap\AFF1^{Cterm.Scer\UAS.T:Hsap\MYC} Hsap\MLL::Hsap\AFF1^Scer\UAS.cMa Hsap\MLL::Hsap\MLLT3^{Scer\UAS.C.T:Zzzz\FLAG} Hsap\MLL^{Nterm.Scer\UAS.T:Hsap\MYC} Hsap\MLL^{Scer\UAS.C.T:Zzzz\FLAG} Hsap\MLLT3^{Cterm.Scer\UAS.T:Hsap\MYC} Scer\GAL4⁵⁰¹⁵ Scer\GAL4^Act5C.PU Scer\GAL4^arm.PS Scer\GAL4^Cg.PA Scer\GAL4^da.G32 Scer\GAL4^Dot.PK Scer\GAL4^en-e16E Scer\GAL4^gcm.PU Scer\GAL4^{mat.αTub67C.T:Hsim\VP16} Scer\GAL4^MZ1580 Scer\GAL4^T80 trx^B11 trx^E3 trx^JY16
Constructs (13)
	P{Act5C-GAL4.U} P{Cg-GAL4.A} P{Dot-GAL4.K} P{GAL4-arm.S} P{GAL4-da.G32} P{gcm-GAL4.U} P{matα4-GAL-VP16} P{UAS-AF4.Cterm.MYC} P{UAS-AF9.Cterm.MYC} P{UAS-MLL.C.FLAG} P{UAS-MLL.Nterm.MYC} P{UAS-MLL-AF4} P{UAS-MLL-AF9.FLAG}
Genes (9)
	Hsap\AFF1 Hsap\MLL Hsap\MLL::Hsap\AFF1 Hsap\MLL::Hsap\MLLT3 Hsap\MLLT3 Scer\GAL4 T:Hsap\MYC T:Zzzz\FLAG trx
Insertions (4)
	P{en2.4-GAL4}e16E P{GawB}5015 P{GawB}MZ1580 P{GawB}T80
Natural transposons (1)
	P-element