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J Clin Invest. 2009 Jun;119(6):1714-26. doi: 10.1172/JCI38248. Epub 2009 May 18.

High throughput digital quantification of mRNA abundance in primary human acute myeloid leukemia samples.

Author information

1
Department of Pathology and Immunology, Division of Laboratory and Genomic Medicine, Washington University Medical School, St. Louis, Missouri 63110, USA.

Abstract

Acute promyelocytic leukemia (APL) is characterized by the t(15;17) chromosomal translocation, which results in fusion of the retinoic acid receptor alpha (RARA) gene to another gene, most commonly promyelocytic leukemia (PML). The resulting fusion protein, PML-RARA, initiates APL, which is a subtype (M3) of acute myeloid leukemia (AML). In this report, we identify a gene expression signature that is specific to M3 samples; it was not found in other AML subtypes and did not simply represent the normal gene expression pattern of primary promyelocytes. To validate this signature for a large number of genes, we tested a recently developed high throughput digital technology (NanoString nCounter). Nearly all of the genes tested demonstrated highly significant concordance with our microarray data (P < 0.05). The validated gene signature reliably identified M3 samples in 2 other AML datasets, and the validated genes were substantially enriched in our mouse model of APL, but not in a cell line that inducibly expressed PML-RARA. These results demonstrate that nCounter is a highly reproducible, customizable system for mRNA quantification using limited amounts of clinical material, which provides a valuable tool for biomarker measurement in low-abundance patient samples.

PMID:
19451695
PMCID:
PMC2689138
DOI:
10.1172/JCI38248
[Indexed for MEDLINE]
Free PMC Article

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