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Digital gene expression profiling of primary acute lymphoblastic leukemia cells
Uppsala University, Sweden .
Uppsala University, Sweden .
Uppsala University, Sweden .
Uppsala University, Sweden .
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2012 (English)In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 26, no 6, 1218-1227 p.Article in journal (Refereed) Published
Abstract [en]

We determined the genome-wide digital gene expression (DGE) profiles of primary acute lymphoblastic leukemia (ALL) cells from 21 patients taking advantage of `second-generation sequencing technology. Patients included in this study represent four cytogenetically distinct subtypes of B-cell precursor (BCP) ALL and T-cell lineage ALL (T-ALL). The robustness of DGE combined with supervised classification by nearest shrunken centroids (NSC) was validated experimentally and by comparison with published expression data for large sets of ALL samples. Genes that were differentially expressed between BCP ALL subtypes were enriched to distinct signaling pathways with dic(9;20) enriched to TP53 signaling, t(9;22) to interferon signaling, as well as high hyperdiploidy and t(12;21) to apoptosis signaling. We also observed antisense tags expressed from the non-coding strand of similar to 50% of annotated genes, many of which were expressed in a subtype-specific pattern. Antisense tags from 17 gene regions unambiguously discriminated between the BCP ALL and T-ALL subtypes, and antisense tags from 76 gene regions discriminated between the 4 BCP subtypes. We observed a significant overlap of gene regions with alternative polyadenylation and antisense transcription (Pless than1 x 10(-15)). Our study using DGE profiling provided new insights into the RNA expression patterns in ALL cells.

Place, publisher, year, edition, pages
Nature Publishing Group , 2012. Vol. 26, no 6, 1218-1227 p.
Keyword [en]
pediatric acute lymphoblastic leukemia; ALL; digital gene expression; second-generation sequencing; antisense transcript; alternative polyadenylation
National Category
Social Sciences
URN: urn:nbn:se:liu:diva-79818DOI: 10.1038/leu.2011.358ISI: 000305081000009OAI: diva2:544962
Available from: 2012-08-17 Created: 2012-08-14 Last updated: 2014-09-10

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