title: Identification of a novel, tissue-specific ABCG2 promoter expressed in pediatric acute megakaryoblastic leukemia.
abstract: ABCG2 encodes a transporter protein that is associated with multidrug-resistant phenotypes in many cancers, including acute myeloid leukemia (AML); high levels of expression are generally associated with a poor prognosis. To better understand how expression of ABCG2 is controlled in pediatric AML, we performed a detailed analysis of the ABCG2 transcript isoforms from a variety of tissue sources, including 85 pediatric AML samples. These studies revealed a complex 5' untranslated region (UTR) with 6 novel exons and multiple splice variants. Samples from children with acute megakaryoblastic leukemia (AML FAB-M7) not associated with Down syndrome showed uniformly higher levels of ABCG2 transcripts than samples from children with other AML subtypes. A novel 5' UTR identified 90kb upstream of the exon 2 translation initiation site was expressed only in M7 AML subtypes. An associated upstream promoter fragment was shown to be selectively expressed in megakaryoblastic leukemia cells but not in human epithelial cell lines. These findings identify a new tissue-specific ABCG2 promoter that is selectively expressed in pediatric M7 AML. We also show a relatively high incidence of ABCG2 mRNA expression in non-Down associated M7 AML, which may contribute to the relatively poor prognosis of the M7 AML subtype.
authors.affiliation: Division of Leukemia/Lymphoma, St. Jude Children's Research Hospital, Memphis, TN, USA.
authors.forename: Patrick K
authors.initials: PK
authors.lastname: Campbell
authors.forename: Yang
authors.initials: Y
authors.lastname: Zong
authors.forename: Shengping
authors.initials: S
authors.lastname: Yang
authors.forename: Sheng
authors.initials: S
authors.lastname: Zhou
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Rubnitz
authors.forename: Brian P
authors.initials: BP
authors.lastname: Sorrentino
mesh_terms: D024506:5' Flanking Region; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000293:Adolescent; D017398:Alternative Splicing; D001483:Base Sequence; D015139:Blotting, Southern; D002648:Child; D002675:Child, Preschool; D005091:Exons; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D020014:K562 Cells; D016086:Lentivirus; D007947:Leukemia, Megakaryoblastic, Acute / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics*; D009928:Organ Specificity; D010372:Pediatrics; D011379:Prognosis; D020033:Protein Isoforms / Q000235:genetics*; D020871:RNA Stability; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D014162:Transfection; D055815:Young Adult
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D009363:Neoplasm Proteins; D020033:Protein Isoforms