Background: Post-translational modification (PTM) crosstalk is a young research field.
However, there is now evidence of the extraordinary characterization of the different proteoforms
and their interactions in a biological environment that PTM crosstalk studies can describe. Besides
gene expression and phosphorylation profiling of acute myeloid leukemia (AML) samples, the
functional combination of several PTMs that might contribute to a better understanding of the
complexity of the AML proteome remains to be discovered.
Objective: By reviewing current workflows for the simultaneous enrichment of several PTMs and
bioinformatics tools to analyze mass spectrometry (MS)-based data, our major objective is to introduce
the PTM crosstalk field to the AML research community.
Results: After an introduction to PTMs and PTM crosstalk, this review introduces several protocols
for the simultaneous enrichment of PTMs. Two of them allow a simultaneous enrichment of at
least three PTMs when using 0.5-2 mg of cell lysate. We have reviewed many of the bioinformatics
tools used for PTM crosstalk discovery as its complex data analysis, mainly generated from
MS, becomes challenging for most AML researchers. We have presented several non-AML PTM
crosstalk studies throughout the review in order to show how important the characterization of
PTM crosstalk becomes for the selection of disease biomarkers and therapeutic targets.
Conclusion: Herein, we have reviewed the advances and pitfalls of the emerging PTM crosstalk
field and its potential contribution to unravel the heterogeneity of AML. The complexity of sample
preparation and bioinformatics workflows demands a good interaction between experts of several