Quantitative comparison of the expression of EVI1 and its presumptive antagonist, MDS1/EVI1, in patients with myeloid leukemia.
The EVI1 gene in chromosome band 3q26 exhibits a number of properties consistent with a role as an oncogene, and its expression is activated in most myeloid leukemia patients with, as well as in a minority of patients without, 3q26 rearrangements. A splice variant of this gene, MDS1/EVI1, acts as its antagonist at least in some tissue culture assays. We established real-time quantitative reverse transcriptase polymerase chain reaction (RTQ-RT-PCR) assays for these mRNA variants to compare their expression levels in a quantitatively reliable manner. EVI1 was overexpressed to highly variable extents in all patients with, as well as in 14% of patients without, 3q26 rearrangements. In some of these samples, MDS1/EVI1 was also transcribed at elevated levels compared to those of healthy controls. However, although the induction of MDS1/EVI1 was comparable to, or higher than, that of EVI1 in three of five samples with a normal EVI1 locus, this was true for only two of 13 patients with a 3q26 aberration. We further provide preliminary evidence that the RTQ-RT-PCR assay may be useful for disease monitoring in patients overexpressing EVI1.
Vinatzer
Ursula
U
Institut für Medizinische Biologie der Universitaet Wien, Vienna, Austria.
Mannhalter
Christine
C
Mitterbauer
Margit
M
Gruener
Helga
H
Greinix
Hildegard
H
Schmidt
Helmut H
HH
Fonatsch
Christa
C
Wieser
Rotraud
R
D000328:Adult; D000368:Aged; D017398:Alternative Splicing / Q000235:genetics; D002648:Child; D002869:Chromosome Aberrations; D002871:Chromosome Banding; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D021983:Cyclophilins / Q000235:genetics; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000235:genetics; D018450:Disease Progression; D005260:Female; D006801:Humans; D020014:K562 Cells; D007951:Leukemia, Myeloid / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000074008:MDS1 and EVI1 Complex Locus Protein; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D015514:Oncogene Proteins, Fusion; D011519:Proto-Oncogenes; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D014407:Tumor Cells, Cultured; D020298:U937 Cells
D004268:DNA-Binding Proteins; D000074008:MDS1 and EVI1 Complex Locus Protein; C098704:MDS1-EVI1 fusion protein, human; C063575:MECOM protein, human; D015514:Oncogene Proteins, Fusion; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D021983:Cyclophilins