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.

journal_name

Leuk Res

journal_title

Leukemia research

authors

Campbell PK,Zong Y,Yang S,Zhou S,Rubnitz JE,Sorrentino BP

doi

10.1016/j.leukres.2011.05.004

subject

Has Abstract

pub_date

2011-10-01 00:00:00

pages

1321-9

issue

10

eissn

0145-2126

issn

1873-5835

pii

S0145-2126(11)00221-9

journal_volume

35

pub_type

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