title: Digital gene expression profiling of primary acute lymphoblastic leukemia cells.
abstract: 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 ~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 (P<1 × 10(-15)). Our study using DGE profiling provided new insights into the RNA expression patterns in ALL cells.
authors.affiliation: Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Nordlund
authors.forename: A
authors.initials: A
authors.lastname: Kiialainen
authors.forename: O
authors.initials: O
authors.lastname: Karlberg
authors.forename: E C
authors.initials: EC
authors.lastname: Berglund
authors.forename: H
authors.initials: H
authors.lastname: Göransson-Kultima
authors.forename: M
authors.initials: M
authors.lastname: Sønderkær
authors.forename: K L
authors.initials: KL
authors.lastname: Nielsen
authors.forename: M G
authors.initials: MG
authors.lastname: Gustafsson
authors.forename: M
authors.initials: M
authors.lastname: Behrendtz
authors.forename: E
authors.initials: E
authors.lastname: Forestier
authors.forename: M
authors.initials: M
authors.lastname: Perkkiö
authors.forename: S
authors.initials: S
authors.lastname: Söderhäll
authors.forename: G
authors.initials: G
authors.lastname: Lönnerholm
authors.forename: A-C
authors.initials: AC
authors.lastname: Syvänen
mesh_terms: D000293:Adolescent; D014408:Biomarkers, Tumor / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D007223:Infant; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger