EVI1 overexpression in t(3;17) positive myeloid malignancies results from juxtaposition of EVI1 to the MSI2 locus at 17q22.
Chromosomal translocations involving the EVI1 locus are a recurrent finding in myeloid leukemia and are associated with poor prognosis. In this study, we performed a detailed molecular characterization of the recurrent translocation t(3;17)(q26;q22) in 13 hematologic malignancies. The EVI1 gene locus was rearranged in all 13 patients and was associated with EVI1 overexpression. In 9 out of 13 patients, the 17q breakpoints clustered in a 250 kb region on band 17q22 encompassing the MSI2 (musashi homologue 2) gene. Expression analyses failed to demonstrate ectopic MSI2 expression or the presence of an MSI2/EVI1 fusion gene. In conclusion, we show for the first time that the t(3;17) is indeed a recurrent chromosomal aberration in myeloid malignancies. In keeping with findings in other recurrent 3q26 rearrangements, overexpression of the EVI1 gene appears to be the major contributor to leukemogenesis in patients with a t(3;17).
De Weer
An
A
Centre for Medical Genetics Gent, Ghent University Hospital, Ghent, Belgium.
Speleman
Frank
F
Cauwelier
Barbara
B
Van Roy
Nadine
N
Yigit
Nurten
N
Verhasselt
Bruno
B
De Moerloose
Barbara
B
Benoit
Yves
Y
Noens
Lucien
L
Selleslag
Dominik
D
Lippert
Eric
E
Struski
Stephanie
S
Bastard
Christian
C
De Paepe
Anne
A
Vandenberghe
Peter
P
Hagemeijer
Anne
A
Dastugue
Nicole
N
Poppe
Bruce
B
D002886:Chromosomes, Human, Pair 17; D002893:Chromosomes, Human, Pair 3; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics*; D006801:Humans; D000074008:MDS1 and EVI1 Complex Locus Protein; D009196:Myeloproliferative Disorders / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D011519:Proto-Oncogenes / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics*; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics*; D014178:Translocation, Genetic
D004268:DNA-Binding Proteins; D000074008:MDS1 and EVI1 Complex Locus Protein; C063575:MECOM protein, human; C438151:MSI2 protein, human; D015514:Oncogene Proteins, Fusion; D016601:RNA-Binding Proteins; D014157:Transcription Factors