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Subject Item
n2:RIV%2F00064203%3A_____%2F11%3A6958%21RIV12-MZ0-00064203
rdf:type
n9:Vysledek skos:Concept
rdfs:seeAlso
http://www.ncbi.nlm.nih.gov/pubmed/20971820
dcterms:description
Background Pediatric acute myeloid leukemia is a heterogeneous disease characterized by non-random genetic aberrations related to outcome. The genetic subtype is currently detected by different diagnostic procedures which differ in success rate and/or specificity. Design and Methods We examined the potential of gene expression profiles to classify pediatric acute myeloid leukemia. Gene expression microarray data of 237 children with acute myeloid leukemia were collected and a double-loop cross validation approach was used to generate a subtype-predictive gene expression profile in the discovery cohort (n=157) which was then tested for its true predictive value in the independent validation cohort (n=80). The classifier consisted of 75 probe sets, representing the top 15 discriminating probe sets for MLL-rearranged, t(8;21)(q22;q22), inv(16)(p13q22), t(15;17)(q21;q22) and t(7;12)(q36;p13)-positive acute myeloid leukemia. Results These cytogenetic subtypes represent approximately 40% of cases of pediatric acute myeloid leukemia and were predicted with 92% and 99% accuracy in the discovery and independent validation cohort, respectively. However, for NPM1, CEBPA, MLL(-PTD), FLT3(-ITD), KIT, PTPN11 and N/K-RAS gene expression signatures had limited predictive value. This may be caused by a limited frequency of these mutations and by underlying cytogenetics. This latter is exemplified by the fact that different gene expression signatures were discovered for FLT3-ITD in patients with normal cytogenetics and in those with t(15;17)(q21;q22)-positive acute myeloid leukemia, which pointed to HOXB-upregulation being specific for FLT3-ITD+ cytogenetically normal acute myeloid leukemia. Conclusions In conclusion, gene expression profiling correctly predicted the most prevalent cytogenetic subtypes of pediatric acute myeloid leukemia with high accuracy. In clinical practice, this gene expression signature may replace multiple diagnostic tests for approximately 40% of pediatric ac Background Pediatric acute myeloid leukemia is a heterogeneous disease characterized by non-random genetic aberrations related to outcome. The genetic subtype is currently detected by different diagnostic procedures which differ in success rate and/or specificity. Design and Methods We examined the potential of gene expression profiles to classify pediatric acute myeloid leukemia. Gene expression microarray data of 237 children with acute myeloid leukemia were collected and a double-loop cross validation approach was used to generate a subtype-predictive gene expression profile in the discovery cohort (n=157) which was then tested for its true predictive value in the independent validation cohort (n=80). The classifier consisted of 75 probe sets, representing the top 15 discriminating probe sets for MLL-rearranged, t(8;21)(q22;q22), inv(16)(p13q22), t(15;17)(q21;q22) and t(7;12)(q36;p13)-positive acute myeloid leukemia. Results These cytogenetic subtypes represent approximately 40% of cases of pediatric acute myeloid leukemia and were predicted with 92% and 99% accuracy in the discovery and independent validation cohort, respectively. However, for NPM1, CEBPA, MLL(-PTD), FLT3(-ITD), KIT, PTPN11 and N/K-RAS gene expression signatures had limited predictive value. This may be caused by a limited frequency of these mutations and by underlying cytogenetics. This latter is exemplified by the fact that different gene expression signatures were discovered for FLT3-ITD in patients with normal cytogenetics and in those with t(15;17)(q21;q22)-positive acute myeloid leukemia, which pointed to HOXB-upregulation being specific for FLT3-ITD+ cytogenetically normal acute myeloid leukemia. Conclusions In conclusion, gene expression profiling correctly predicted the most prevalent cytogenetic subtypes of pediatric acute myeloid leukemia with high accuracy. In clinical practice, this gene expression signature may replace multiple diagnostic tests for approximately 40% of pediatric ac
dcterms:title
Evaluation of gene expression signatures predictive of cytogenetic and molecular subtypes of pediatric acute myeloid leukemia Evaluation of gene expression signatures predictive of cytogenetic and molecular subtypes of pediatric acute myeloid leukemia
skos:prefLabel
Evaluation of gene expression signatures predictive of cytogenetic and molecular subtypes of pediatric acute myeloid leukemia Evaluation of gene expression signatures predictive of cytogenetic and molecular subtypes of pediatric acute myeloid leukemia
skos:notation
RIV/00064203:_____/11:6958!RIV12-MZ0-00064203
n9:predkladatel
n10:ico%3A00064203
n3:aktivita
n16:I n16:P
n3:aktivity
I, P(OC09051)
n3:cisloPeriodika
2
n3:dodaniDat
n5:2012
n3:domaciTvurceVysledku
n13:1071718 n13:4977939
n3:druhVysledku
n18:J
n3:duvernostUdaju
n19:S
n3:entitaPredkladatele
n11:predkladatel
n3:idSjednocenehoVysledku
198309
n3:idVysledku
RIV/00064203:_____/11:6958
n3:jazykVysledku
n14:eng
n3:klicovaSlova
pediatric acute myeloid leukemia; gene expression profile; cytogenetic subtype; classification; microarray; acute lymphoblastic-leukemia; internal tandem duplication; acute myelogenous leukemia; minimal-residual-disease; normal karyotype; prognostic-significance; cebpa mutations; group-b; aml 10; flt3
n3:klicoveSlovo
n4:microarray n4:minimal-residual-disease n4:normal%20karyotype n4:cytogenetic%20subtype n4:prognostic-significance n4:group-b n4:pediatric%20acute%20myeloid%20leukemia n4:cebpa%20mutations n4:gene%20expression%20profile n4:internal%20tandem%20duplication n4:aml%2010 n4:acute%20myelogenous%20leukemia n4:flt3 n4:classification n4:acute%20lymphoblastic-leukemia
n3:kodStatuVydavatele
GB - Spojené království Velké Británie a Severního Irska
n3:kontrolniKodProRIV
[50D7236FB766]
n3:nazevZdroje
Haematologica-The Hematology Journal
n3:obor
n15:FD
n3:pocetDomacichTvurcuVysledku
2
n3:pocetTvurcuVysledku
20
n3:projekt
n17:OC09051
n3:rokUplatneniVysledku
n5:2011
n3:svazekPeriodika
96
n3:tvurceVysledku
Starý, Jan van Wering, ER Baruchel, A. Meyer, C. Van den Heuvel-Eibrink, MM Arentsen-Peters, STJCM Cayuela, JM Cloos, J. de Bont, ESJM Hollink, IHIM den Boer, M. L. Beverloo, H. B. Marschalek, R. Trka, Jan Pieters, R. De Menezes, RX Balgobind, BV Kaspers, GJL Reinhardt, D. Zwaan, CM
n3:wos
000287766500009
s:issn
0390-6078
s:numberOfPages
10