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Pontin is a critical regulator for AML1-ETO-induced leukemia

Lookup NU author(s): Professor Olaf Heidenreich


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The oncogenic fusion protein AML1-ETO, also known as RUNX1-RUNX1T1 is generated by the t(8; 21)(q22; q22) translocation, one of the most frequent chromosomal rearrangements in acute myeloid leukemia (AML). Identifying the genes that cooperate with or are required for the oncogenic activity of this chimeric transcription factor remains a major challenge. Our previous studies showed that Drosophila provides a genuine model to study how AML1-ETO promotes leukemia. Here, using an in vivo RNA interference screen for suppressors of AML1-ETO activity, we identified pontin/RUVBL1 as a gene required for AML1-ETO-induced lethality and blood cell proliferation in Drosophila. We further show that PONTIN inhibition strongly impaired the growth of human t(8; 21) or AML1-ETO-expressing leukemic blood cells. Interestingly, AML1-ETO promoted the transcription of PONTIN. Moreover, transcriptome analysis in Kasumi-1 cells revealed a strong correlation between PONTIN and AML1-ETO gene signatures and demonstrated that PONTIN chiefly regulated the expression of genes implicated in cell cycle progression. Concordantly, PONTIN depletion inhibited leukemic self-renewal and caused cell cycle arrest. All together our data suggest that the upregulation of PONTIN by AML1-ETO participate in the oncogenic growth of t(8; 21) cells.

Publication metadata

Author(s): Breig O, Bras S, Soria NM, Osman D, Heidenreich O, Haenlin M, Waltzer L

Publication type: Article

Publication status: Published

Journal: Leukemia

Year: 2014

Volume: 28

Issue: 6

Pages: 1271-1279

Print publication date: 01/06/2014

Online publication date: 14/01/2014

Acceptance date: 11/12/2013

ISSN (print): 0887-6924

ISSN (electronic): 1476-5551

Publisher: Nature Publishing Group


DOI: 10.1038/leu.2013.376


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Funder referenceFunder name
Association for International Cancer Research
Fondation ARC
Fondation pour la Recherche Medicale
Ligue Regionale Midi Pyrenees
10033Leukaemia and Lymphoma Research