Identification of a novel, tissue-specific ABCG2 promoter expressed in pediatric acute megakaryoblastic leukemia.
Leuk Res
; 35(10): 1321-9, 2011 Oct.
Article
em En
| MEDLINE
| ID: mdl-21640380
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transcrição Gênica
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Leucemia Megacarioblástica Aguda
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Regulação Neoplásica da Expressão Gênica
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Transportadores de Cassetes de Ligação de ATP
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Isoformas de Proteínas
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Proteínas de Neoplasias
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Adolescent
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Adult
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Child
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Child, preschool
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Humans
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Infant
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Newborn
Idioma:
En
Revista:
Leuk Res
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Estados Unidos