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Expression of four major WT1 splicing variants in acute and chronic myeloid leukemia patients analyzed by newly developed four real-time RT PCRs
T. Lopotová, J. Polák, J. Schwarz, H. Klamová, J. Moravcová
Language English Country United States
Document type Clinical Trial, Comparative Study, Journal Article, Research Support, Non-U.S. Gov't
Grant support
NT12392
MZ0
CEP Register
- MeSH
- Leukemia, Myeloid, Acute diagnosis metabolism therapy MeSH
- Alternative Splicing MeSH
- K562 Cells MeSH
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive diagnosis metabolism therapy MeSH
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Reverse Transcriptase Polymerase Chain Reaction MeSH
- WT1 Proteins biosynthesis MeSH
- Gene Expression Regulation, Leukemic MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial MeSH
- Research Support, Non-U.S. Gov't MeSH
- Comparative Study MeSH
Although the mechanism of action of leukemic oncogene Wilms' tumor gene 1 (WT1) remains unclear, WT1 has already been used in monitoring of patients with acute myeloid leukemia (AML) and it is being tested for immunotherapy. More detailed understanding of the role of WT1 in leukemia may improve its utilization. At least 36 isoforms may be produced. Four major variants denoted as -5/-KTS, -5/+KTS, +5/-KTS and +5/+KTS are produced by combining splicing of exon 5 and KTS sequence. In this study, we report applicability of newly developed real-time RT PCRs enabling for the first time full quantification of the four major WT1 splicing variants. Following careful optimization and testing of quantification reliability of four assays, we analyzed 34 samples of patients with AML and 12 samples of patients with chronic myeloid leukemia (CML) at the time of diagnosis. Analyses of five more CML patients provided insight into WT1 variants expression kinetics. We found predominance of +5/+KTS in both diagnoses. Comparison of WT1 variant expression in AML and CML patients' groups differing in response to therapy suggested possible importance of particular WT1 variant levels as markers of further disease course.
References provided by Crossref.org
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