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A standardized microarray assay for the independent gene expression markers in AML: EVI1 and BAALC

High levels of BAALC, ERG, EVI1 and MN1 expression have been associated with shorter overall survival in AML but standardized and clinically validated assays are lacking. We have therefore developed and optimized an assay for standardized detection of these prognostic genes for patients with interme...

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Autores principales: Brand, Jaap, van Vliet, Martin H, de Best, Leonie, Valk, Peter JM, Viëtor, Henk E, Löwenberg, Bob, van Beers, Erik H
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3605258/
https://www.ncbi.nlm.nih.gov/pubmed/23497432
http://dx.doi.org/10.1186/2162-3619-2-7
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author Brand, Jaap
van Vliet, Martin H
de Best, Leonie
Valk, Peter JM
Viëtor, Henk E
Löwenberg, Bob
van Beers, Erik H
author_facet Brand, Jaap
van Vliet, Martin H
de Best, Leonie
Valk, Peter JM
Viëtor, Henk E
Löwenberg, Bob
van Beers, Erik H
author_sort Brand, Jaap
collection PubMed
description High levels of BAALC, ERG, EVI1 and MN1 expression have been associated with shorter overall survival in AML but standardized and clinically validated assays are lacking. We have therefore developed and optimized an assay for standardized detection of these prognostic genes for patients with intermediate cytogenetic risk AML. In a training set of 147 intermediate cytogenetic risk cases we performed cross validations at 5 percentile steps of expression level and observed a bimodal significance profile for BAALC expression level and unimodal significance profiles for ERG and MN1 levels with no statistically significant cutoff points near the median expression level of BAALC, ERG or MN1. Of the possible cutoff points for expression levels of BAALC, ERG and MN1, just the 30th and 75th percentile of BAALC expression level and the 30th percentile of MN1 expression level cutoff points showed clinical significance. Of these only the 30th percentile of BAALC expression level reproduced in an independent verification (extended training) data set of 242 cytogenetically normal AML cases and successfully validated in an external cohort of 215 intermediate cytogenetic risk AML cases. Finally, we show independent prognostic value for high EVI1 and low BAALC in multivariate analysis with other clinically relevant molecular AML markers. We have developed a highly standardized molecular assay for the independent gene expression markers EVI1 and BAALC.
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spelling pubmed-36052582013-03-22 A standardized microarray assay for the independent gene expression markers in AML: EVI1 and BAALC Brand, Jaap van Vliet, Martin H de Best, Leonie Valk, Peter JM Viëtor, Henk E Löwenberg, Bob van Beers, Erik H Exp Hematol Oncol Research High levels of BAALC, ERG, EVI1 and MN1 expression have been associated with shorter overall survival in AML but standardized and clinically validated assays are lacking. We have therefore developed and optimized an assay for standardized detection of these prognostic genes for patients with intermediate cytogenetic risk AML. In a training set of 147 intermediate cytogenetic risk cases we performed cross validations at 5 percentile steps of expression level and observed a bimodal significance profile for BAALC expression level and unimodal significance profiles for ERG and MN1 levels with no statistically significant cutoff points near the median expression level of BAALC, ERG or MN1. Of the possible cutoff points for expression levels of BAALC, ERG and MN1, just the 30th and 75th percentile of BAALC expression level and the 30th percentile of MN1 expression level cutoff points showed clinical significance. Of these only the 30th percentile of BAALC expression level reproduced in an independent verification (extended training) data set of 242 cytogenetically normal AML cases and successfully validated in an external cohort of 215 intermediate cytogenetic risk AML cases. Finally, we show independent prognostic value for high EVI1 and low BAALC in multivariate analysis with other clinically relevant molecular AML markers. We have developed a highly standardized molecular assay for the independent gene expression markers EVI1 and BAALC. BioMed Central 2013-03-06 /pmc/articles/PMC3605258/ /pubmed/23497432 http://dx.doi.org/10.1186/2162-3619-2-7 Text en Copyright ©2013 Brand et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Brand, Jaap
van Vliet, Martin H
de Best, Leonie
Valk, Peter JM
Viëtor, Henk E
Löwenberg, Bob
van Beers, Erik H
A standardized microarray assay for the independent gene expression markers in AML: EVI1 and BAALC
title A standardized microarray assay for the independent gene expression markers in AML: EVI1 and BAALC
title_full A standardized microarray assay for the independent gene expression markers in AML: EVI1 and BAALC
title_fullStr A standardized microarray assay for the independent gene expression markers in AML: EVI1 and BAALC
title_full_unstemmed A standardized microarray assay for the independent gene expression markers in AML: EVI1 and BAALC
title_short A standardized microarray assay for the independent gene expression markers in AML: EVI1 and BAALC
title_sort standardized microarray assay for the independent gene expression markers in aml: evi1 and baalc
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3605258/
https://www.ncbi.nlm.nih.gov/pubmed/23497432
http://dx.doi.org/10.1186/2162-3619-2-7
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