Anti-PML-RARα shRNA sensitises promyelocytic leukaemia cells to all-trans retinoic acid


Research Report

J RNAi Gene Silencing (2012), 8, 464-469

doi: jrgsxx

Published online: 13 July 2012

Full Text: (pdf ~635kb)

Anti-PML-RARα shRNA sensitises promyelocytic leukaemia cells to all-trans retinoic acid

Nicholas P Casey and Gregory M Woods

Menzies Research Institute, University of Tasmania, Medical Science 1, 17 Liverpool Street, Hobart TAS 7000, Australia

*Correspondence toGreory Woods, Email: G.M.Woods@utas.edu.au, or Nicholas Casey, Email: npcasey@utas.edu.au, Tel: +61 3 62264832, Fax: +61 3 62264816

Received: 02 February 2012, Revised: 10 July 2012, Accepted: 11 July 2012

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ABSTRACT

The PML-RARα fusion gene disrupts the retinoic acid differentiation signal in a range of leukaemia types, promoting proliferation. We designed a shRNA to target the fusion mRNA, and the shRNA expression cassette was delivered via lentiviral transduction. Delivery of this shRNA significantly down regulated the target mRNA, with effects also evident at the protein level. When combined with ATRA administration, this down regulation of the fusion gene strongly inhibited proliferation in the NB4 PML cell line.

Keywords: Leukaemia, PML, shRNA, lentiviral vector

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