Transcriptomic and proteomic analysis of mouse radiation-induced acute myeloid leukaemia (AML)

// Christophe Badie 1 , Agnieszka Blachowicz 2 , Zarko Barjaktarovic 3 , Rosemary Finnon 1 , Arlette Michaux 4 , Hakan Sarioglu 5 , Natalie Brown 1 , Grainne Manning 1 , M. Abderrafi Benotmane 4 , Soile Tapio 3 , Joanna Polanska 2 , Simon D. Bouffler 1 1 Radiation Effects Department, Centre for Radiation, Chemical and Environmental Hazards, Public Health England, Chilton, UK 2 Faculty of Automatic Control, Electronics and Computer Science, Silesian University of Techology, Gliwice, Poland 3 Helmholtz Zentrum Munchen, German Research Center for Environmental Health GmbH, Radiation Proteomics Group, Institute of Radiation Biology, Neuherberg, Germany 4 Radiobiology Unit, Institute for Environment, Health and Safety, Belgian Nuclear Research Centre (SCK•.CEN), Mol, Belgium 5 Helmholtz Zentrum Munchen, German Research Center for Environmental Health GmbH, Research Unit Protein Science, Neuherberg, Germany Correspondence to: Simon D. Bouffler, email: simon.bouffler@phe.gov.uk Keywords: ionising radiation, acute myeloid leukaemia, mouse, gene expression, protein expression Received: February 11, 2016     Accepted: May 09, 2016     Published: May 26, 2016 ABSTRACT A combined transcriptome and proteome analysis of mouse radiation-induced AMLs using two primary AMLs, cell lines from these primaries, another cell line and its in vivo passage is reported. Compared to haematopoietic progenitor and stem cells (HPSC), over 5000 transcriptome alterations were identified, 2600 present in all materials. 55 and 3 alterations were detected in the proteomes of the cell lines and primary/ in vivo passage material respectively, with one common to all materials. In cell lines, approximately 50% of the transcriptome changes are related to adaptation to cell culture, and in the proteome this proportion was higher. An AML ‘signature’ of 17 genes/proteins commonly deregulated in primary AMLs and cell lines compared to HPSCs was identified and validated using human AML transcriptome data. This also distinguishes primary AMLs from cell lines and includes proteins such as Coronin 1, pontin/RUVBL1 and Myeloperoxidase commonly implicated in human AML. C-Myc was identified as having a key role in radiation leukaemogenesis. These data identify novel candidates relevant to mouse radiation AML pathogenesis, and confirm that pathways of leukaemogenesis in the mouse and human share substantial commonality.