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Acute Leukemias

A new molecular network comprising PU.1, interferon regulatory factor proteins and miR-342 stimulates ATRA-mediated granulocytic differentiation of acute promyelocytic leukemia cells

Leukemia volume 23, pages 856–862 (2009)Cite this article

Abstract

In the acute promyelocytic leukemia (APL) bearing the t(15;17), all-trans-retinoic acid (ATRA) treatment induces granulocytic maturation and complete remission of leukemia. We identified miR-342 as one of the microRNAs (miRNAs) upregulated by ATRA during APL differentiation. This miRNA emerged as a direct transcriptional target of the critical hematopoietic transcription factors PU.1 and interferon regulatory factor (IRF)-1 and IRF-9. IRF-1 maintains miR-342 at low levels, whereas the binding of PU.1 and IRF-9 in the promoter region following retinoic ATRA-mediated differentiation, upregulates miR-342 expression. Moreover, we showed that enforced expression of miR-342 in APL cells stimulated ATRA-induced differentiation. These data identified miR-342 as a new player in the granulocytic differentiation program activated by ATRA in APL.

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Acknowledgements

We thank O Sthandier and M Marchioni for cell cultures and M Arceci for technical assistance. This work was partially supported by grants from: AIRC and AIRC-ROC, Sixth Research Framework Programme of the European Union, Project RIGHT (LSHB-CT-2004 005276) and SIROCCO (Grant LSHG-CT-2006–037900), PRIN and ‘Centro di eccellenza BEMM’.

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Authors and Affiliations

  1. Department of Genetics and Molecular Biology, Institute Pasteur Cenci-Bolognetti, Sapienza University, Rome, Italy

    M L De Marchis, M Ballarino, B Salvatori, M C Puzzolo, I Bozzoni & A Fatica

  2. Institute of Molecular Biology and Pathology, Consiglio Nazionale delle Ricerche, Rome, Italy

    I Bozzoni

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  1. M L De Marchis
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  2. M Ballarino
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  3. B Salvatori
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  4. M C Puzzolo
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  5. I Bozzoni
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  6. A Fatica
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Corresponding author

Correspondence to A Fatica.

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Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu)

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De Marchis, M., Ballarino, M., Salvatori, B. et al. A new molecular network comprising PU.1, interferon regulatory factor proteins and miR-342 stimulates ATRA-mediated granulocytic differentiation of acute promyelocytic leukemia cells. Leukemia 23, 856–862 (2009). https://doi.org/10.1038/leu.2008.372

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