Investigation Title Transcription profiling of human acute lymphoblastic leukemia samples for diagnostic purposes Comment[Submitted Name] Expression data for diagnosis acute lymphoblastic leukemia samples Experimental Design unknown_experiment_design_type transcription profiling by array Experimental Design Term Source REF EFO Comment[ArrayExpressReleaseDate] 2008-10-26 Comment[SecondaryAccession] GSE12995 Comment[AEMIAMESCORE] 3 Comment[ArrayExpressAccession] E-GEOD-12995 Comment[MAGETAB TimeStamp_Version] 2010-07-30 12:37:24 Last Changed Rev: 13058 Experimental Factor Name Experimental Factor Type Experimental Factor Term Source REF Person Last Name Song Person First Name Guangchun Person Mid Initials Person Email guangchun.song@stjude.org Person Phone Person Fax Person Address Downing, Pathology, St Jude Children's Research Hospital, 332 N Lauderdale, Memphis, 38105, USA Person Affiliation St Jude Children's Research Hospital Person Roles submitter Person Roles Term Source REF The MGED Ontology Quality Control Type Quality Control Term Source REF Replicate Type Replicate Term Source REF Normalization Type Normalization Term Source REF Date of Experiment Public Release Date 2008-10-26 PubMed ID Publication DOI Publication Author List Publication Title Publication Status Publication Status Term Source REF Experiment Description We studied a cohort of 221 high-risk pediatric B-progenitor ALL patients that excluded known high risk ALL subtypes (BCR-ABL1 and infant ALL), using Affymetrix single nucleotide polymorphism microarrays, gene expression profiling and candidate gene resequencing. A CNA poor outcome predictor was identified using a semi-supervised principal components approach, and tested in an independent validation cohort of 258 pediatric B-progenitor ALL cases. Over 50 regions of recurring somatically acquired CNA, with the most frequently targeted genes encoding regulators of B-lymphoid development (66.8% of cases; with PAX5 targeted in 31.7% and IKZF1 in 28.6%). A CNA classifier identified a very poor outcome subgroup in the high-risk cohort (P=4.2x10-5) and was strongly associated with the presence of deletions involving IKZF1, which encodes the early lymphoid transcription factor IKAROS. This classifier, and IKZF1 deletions, also predicted poor outcome and elevated minimal residual disease at the end of induction therapy in the validation cohort. The gene expression signature of the poor outcome group was characterized by reduced expression of B lineage specific genes, and was highly related to the expressing signature of BCR-ABL1 ALL, a known high-risk ALL subtype also characterized by a high frequency of IKZF1 deletion.Somatically acquired deletions involving IKZF1 identify a very poor outcome subgroup of pediatric ALL patients. Incorporation of molecular tests to identify IKZF1 deletion in diagnostic leukemic blasts should improve the ability to accurately risk stratify patients for appropriate therapy. Affymetrix U133A arrays were performed according to the maufacturers directions on RNA extracted from cryopreserved diagnostic bone marrow or peripheral blood samples. Samples with less than 80% blasts were flow sorted prior to RNA extraction Experiment Overall Design: One hundred seventy five pediatric B-progenitor ALL samples were studied using either Affymetrix U133A Protocol Name P-G12995-1 P-G12995-3 P-G12995-2 Affymetrix:Protocol:Hybridization-Unknown P-AFFY-6 Protocol Type grow nucleic_acid_extraction labeling hybridization feature_extraction Protocol Description Cryopreserved peripheral blood or bone marrow samples obtained at diagnosis Trizol extraction of total RNA was performed according to the manufacturer's instructions. As per manufacturer (Affymetrix) Title: Affymetrix Generic Hybridization. Description: Title: Affymetrix CEL analysis. Description: Protocol Parameters Protocol Hardware Protocol Software MicroArraySuite 5.0 MicroArraySuite 5.0 Protocol Contact Protocol Term Source REF mo SDRF File E-GEOD-12995.sdrf.txt Term Source Name mo The MGED Ontology ArrayExpress EFO The MGED Ontology mo Term Source File http://mged.sourceforge.net/ontologies/MGEDontology.php http://mged.sourceforge.net/ontologies/MGEDontology.php http://www.ebi.ac.uk/arrayexpress http://www.ebi.ac.uk/efo/ http://mged.sourceforge.net/ontologies/MGEDontology.php http://mged.sourceforge.net/ontologies/MGEDontology.php Term Source Version