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- Title
High throughput digital quantification of mRNA abundance in primary human acute myeloid leukemia samples.
- Authors
Payton, Jacqueline E.; Grieselhuber, Nicole R.; Li-Wei Chang; Murakami, Mark; Geiss, Gary K.; Link, Daniel C.; Nagarajan, Rakesh; Watson, Mark A.; Ley, Timothy J.; Chang, Li-Wei
- 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.
- Subjects
MESSENGER RNA; MYELOID leukemia; GENE expression; CELL lines; BIOMARKERS; LABORATORY mice; COMPARATIVE studies; GENES; RESEARCH methodology; MEDICAL cooperation; RESEARCH; RESEARCH funding; RNA; SIGNAL processing; EVALUATION research; ACUTE myeloid leukemia; OLIGONUCLEOTIDE arrays
- Publication
Journal of Clinical Investigation, 2009, Vol 119, Issue 6, p1714
- ISSN
0021-9738
- Publication type
journal article
- DOI
10.1172/JCI38248