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

Oncotarget. 2016 Jun 28;7(26):40461-40480. doi: 10.18632/oncotarget.9626.

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.

Keywords: acute myeloid leukaemia; gene expression; ionising radiation; mouse; protein expression.

MeSH terms

  • ATPases Associated with Diverse Cellular Activities / metabolism
  • Algorithms
  • Animals
  • Carrier Proteins / metabolism
  • Cell Line, Tumor
  • DNA Helicases / metabolism
  • Gene Expression Regulation, Leukemic
  • Hematopoietic Stem Cells / metabolism*
  • Humans
  • Leukemia, Myeloid, Acute / metabolism*
  • Leukemia, Myeloid, Acute / pathology
  • Mice
  • Microfilament Proteins / metabolism
  • Neoplasms, Radiation-Induced / metabolism*
  • Neoplasms, Radiation-Induced / pathology
  • Peroxidase / metabolism
  • Proteome*
  • Signal Transduction
  • Transcriptome*

Substances

  • Carrier Proteins
  • Microfilament Proteins
  • Proteome
  • coronin proteins
  • Peroxidase
  • TIP48 protein, mouse
  • ATPases Associated with Diverse Cellular Activities
  • DNA Helicases
  • RUVBL1 protein, human