PIG7, transactivated by AML1, promotes apoptosis and differentiation of leukemia cells with AML1-ETO fusion gene

J. Liu, H. Xing, Y. Chen, Lan Wang, D. Wang, Q. Rao, K. Tang, Z. Tian, K. He, M. Wang, J. Wang

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

AML1, the potent transcription factor in hematopoiesis, is antagonized by AML1-ETO in t(8;21) leukemia. Our previous study showed that the differentiation and apoptosis of Kasumi-1 induced by sodium phenylbutyrate (PB), were accompanied by significant upregulation of PIG7 and AML1b (one of the AML1 isoforms). Here, we further investigated the relationship between AML1b and PIG7, also the effects of PIG7 on leukemia cells. The results demonstrated that exogenous AML1b could upregulate PIG7 expression in HEK-293 and CV-1 cells in sequence-specific and dosage-dependent manners, and this effect was antagonized by AML1-ETO. The specific AML1-binding site required for p53-induced gene 7 (PIG7) transactivation was located between nucleotides 1511 and 1503 in the PIG7 promoter. Overexpression of PIG7 could induce the apoptosis and differentiation of Kasumi-1 and SKNO-1 cells, but showed less effect on NB4 cells directly. Moreover, ectopic expression of PIG7 could sensitize these cell lines to PB or all-trans retinoic acid, respectively, which could then be abrogated by downregulation of PIG7 expression. Furthermore, the primary acute myeloid leukemia cells showed similar response to the ectopic expression of PIG7. In conclusion, PIG7 could be transactivated by AML1, which subsequently induces differentiation and apoptosis of leukemia cells, especially those with AML1-ETO fusion gene.

Original languageEnglish (US)
Pages (from-to)117-126
Number of pages10
JournalLeukemia
Volume26
Issue number1
DOIs
StatePublished - Jan 2012
Externally publishedYes

Fingerprint

Gene Fusion
p53 Genes
Cell Differentiation
Leukemia
Apoptosis
Up-Regulation
Phenylbutyrates
Gene Expression
Hematopoiesis
Myeloid Cells
Tretinoin
Acute Myeloid Leukemia
Transcriptional Activation
Protein Isoforms
Transcription Factors
Down-Regulation
Nucleotides
Binding Sites
Cell Line

Keywords

  • AML1-ETO
  • AML1b
  • apoptosis
  • differentiation
  • PIG7
  • transactivation

ASJC Scopus subject areas

  • Hematology
  • Cancer Research
  • Anesthesiology and Pain Medicine

Cite this

PIG7, transactivated by AML1, promotes apoptosis and differentiation of leukemia cells with AML1-ETO fusion gene. / Liu, J.; Xing, H.; Chen, Y.; Wang, Lan; Wang, D.; Rao, Q.; Tang, K.; Tian, Z.; He, K.; Wang, M.; Wang, J.

In: Leukemia, Vol. 26, No. 1, 01.2012, p. 117-126.

Research output: Contribution to journalArticle

Liu, J, Xing, H, Chen, Y, Wang, L, Wang, D, Rao, Q, Tang, K, Tian, Z, He, K, Wang, M & Wang, J 2012, 'PIG7, transactivated by AML1, promotes apoptosis and differentiation of leukemia cells with AML1-ETO fusion gene', Leukemia, vol. 26, no. 1, pp. 117-126. https://doi.org/10.1038/leu.2011.178
Liu, J. ; Xing, H. ; Chen, Y. ; Wang, Lan ; Wang, D. ; Rao, Q. ; Tang, K. ; Tian, Z. ; He, K. ; Wang, M. ; Wang, J. / PIG7, transactivated by AML1, promotes apoptosis and differentiation of leukemia cells with AML1-ETO fusion gene. In: Leukemia. 2012 ; Vol. 26, No. 1. pp. 117-126.
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