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E-GEOD-12995 - Transcription profiling of human acute lymphoblastic leukemia samples for diagnostic purposes

Status
Submitted on 30 September 2008, released on 26 October 2008, last updated on 10 June 2011
Organism
Homo sapiens
Samples (175)
Array (1)
Protocols (5)
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
Experiment types
transcription profiling by array, unknown experiment type
Contact
MIAME
PlatformsProtocolsVariablesProcessedRaw
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