Abstract
There are a number of leukemogenic protein-tyrosine kinases (PTKs)
associated with leukemic transformation. Although each is linked
with a specific disease their functional activity poses the question
whether they have a degree of commonality in their effects upon target
cells. Exon array analysis of the effects of six leukemogenic PTKs
(BCR/ABL, TEL/PDGFR, FIP1/PDGFRalpha, D816V KIT, NPM/ALK, and FLT3ITD)
revealed few common effects on the transcriptome. It is apparent,
however, that proteome changes are not directly governed by transcriptome
changes. Therefore, we assessed and used a new generation of iTRAQ
tagging, enabling eight-channel relative quantification discovery
proteomics, to analyze the effects of these six leukemogenic PTKs.
Again these were found to have disparate effects on the proteome
with few common targets. BCR/ABL had the greatest effect on the proteome
and had more effects in common with FIP1/PDGFRalpha. The proteomic
effects of the four type III receptor kinases were relatively remotely
related. The only protein commonly affected was eosinophil-associated
ribonuclease 7. Five of six PTKs affected the motility-related proteins
CAPG and vimentin, although this did not correspond to changes in
motility. However, correlation of the proteomics data with that from
the exon microarray not only showed poor levels of correlation between
transcript and protein levels but also revealed alternative patterns
of regulation of the CAPG protein by different oncogenes, illustrating
the utility of such a combined approach.
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