Original Article

Leukemia (2009) 23, 856–862; doi:10.1038/leu.2008.372; published online 8 January 2009

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

M L De Marchis1, M Ballarino1, B Salvatori1, M C Puzzolo1, I Bozzoni1,2 and A Fatica1

  1. 1Department of Genetics and Molecular Biology, Institute Pasteur Cenci-Bolognetti, Sapienza University, Rome, Italy
  2. 2Institute of Molecular Biology and Pathology, Consiglio Nazionale delle Ricerche, Rome, Italy

Correspondence: Dr A Fatica, Department of Genetics and Molecular Biology, Institute Pasteur Cenci-Bolognetti, Sapienza University, Rome 00185, Italy. E-mail: alessandro.fatica@uniroma1.it

Received 3 September 2008; Revised 24 November 2008; Accepted 28 November 2008; Published online 8 January 2009.

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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.

Keywords:

microRNA, APL, ATRA, PU.1, IRF-1, IRF-9

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