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Statements

Subject Item
n2:RIV%2F00064190%3A_____%2F12%3A%230000369%21RIV13-MZ0-00064190
rdf:type
n10:Vysledek skos:Concept
dcterms:description
Wilms' tumor gene 1 (WT1) functions including some contradictory effects may be explained by the presence and interactions of its isoforms, however, their evaluation has been so far complicated by several technical problems. We designed unique quantitative PCR systems for direct quantification of the major WT1 isoforms A[EX5-/KTS-], B[+/-], C[-/+] and D[+/+] and verified their sensitivity, specificity and reproducibility in extensive testing. With this method we evaluated WT1 total and isoform expression in 23 normal bone marrow (BM) samples, 73 childhood acute myeloid leukemia (AML), 20 childhood myelodysplastic syndrome (MDS), 9 childhood severe aplastic anemia (SAA), 30 adult AML and 29 adult MDS patients. WT1 isoform patterns showed differences among these samples and clustered them into groups representing the specific diagnoses (P<0.0001). Isoform profiles were independent of total WT1 expression and possess certain common features-overexpression of isoform D and EX5[+] variants. The KTS[+]/KTS[-] ratio was less variable than the EX5[+]/EX5[-] ratio and differed between children and adults (P<0.001); the EX5[+]/EX5[-] ratio varied between diagnoses (AML vs MDS, P<0.001). These findings bring new insights into WT1 isoform function and suggest that the ratio of WT1 isoforms, particularly EX5 variants, is probably crucial for the process of malignant transformation. Wilms' tumor gene 1 (WT1) functions including some contradictory effects may be explained by the presence and interactions of its isoforms, however, their evaluation has been so far complicated by several technical problems. We designed unique quantitative PCR systems for direct quantification of the major WT1 isoforms A[EX5-/KTS-], B[+/-], C[-/+] and D[+/+] and verified their sensitivity, specificity and reproducibility in extensive testing. With this method we evaluated WT1 total and isoform expression in 23 normal bone marrow (BM) samples, 73 childhood acute myeloid leukemia (AML), 20 childhood myelodysplastic syndrome (MDS), 9 childhood severe aplastic anemia (SAA), 30 adult AML and 29 adult MDS patients. WT1 isoform patterns showed differences among these samples and clustered them into groups representing the specific diagnoses (P<0.0001). Isoform profiles were independent of total WT1 expression and possess certain common features-overexpression of isoform D and EX5[+] variants. The KTS[+]/KTS[-] ratio was less variable than the EX5[+]/EX5[-] ratio and differed between children and adults (P<0.001); the EX5[+]/EX5[-] ratio varied between diagnoses (AML vs MDS, P<0.001). These findings bring new insights into WT1 isoform function and suggest that the ratio of WT1 isoforms, particularly EX5 variants, is probably crucial for the process of malignant transformation.
dcterms:title
Real-time PCR quantification of major Wilms' tumor gene 1 (WT1) isoforms in acute myeloid leukemia, their characteristic expression patterns and possible functional consequences. Real-time PCR quantification of major Wilms' tumor gene 1 (WT1) isoforms in acute myeloid leukemia, their characteristic expression patterns and possible functional consequences.
skos:prefLabel
Real-time PCR quantification of major Wilms' tumor gene 1 (WT1) isoforms in acute myeloid leukemia, their characteristic expression patterns and possible functional consequences. Real-time PCR quantification of major Wilms' tumor gene 1 (WT1) isoforms in acute myeloid leukemia, their characteristic expression patterns and possible functional consequences.
skos:notation
RIV/00064190:_____/12:#0000369!RIV13-MZ0-00064190
n10:predkladatel
n11:ico%3A00064190
n3:aktivita
n9:V n9:P
n3:aktivity
P(NS10488), V
n3:cisloPeriodika
9
n3:dodaniDat
n17:2013
n3:domaciTvurceVysledku
n19:8025452
n3:druhVysledku
n16:J
n3:duvernostUdaju
n8:S
n3:entitaPredkladatele
n14:predkladatel
n3:idSjednocenehoVysledku
164287
n3:idVysledku
RIV/00064190:_____/12:#0000369
n3:jazykVysledku
n15:eng
n3:klicovaSlova
WT1; Wilms' tumor gene 1; leukemia
n3:klicoveSlovo
n5:WT1 n5:Wilms%27%20tumor%20gene%201 n5:leukemia
n3:kodStatuVydavatele
GB - Spojené království Velké Británie a Severního Irska
n3:kontrolniKodProRIV
[8693BDE351E1]
n3:nazevZdroje
Leukemia
n3:obor
n13:FD
n3:pocetDomacichTvurcuVysledku
1
n3:pocetTvurcuVysledku
11
n3:projekt
n4:NS10488
n3:rokUplatneniVysledku
n17:2012
n3:svazekPeriodika
26
n3:tvurceVysledku
Kramarzová, K. Boublíková, Ludmila
s:issn
0887-6924
s:numberOfPages
10
n7:doi
10.1038/leu.2012.76