Protein Post-Translational Modification Crosstalk in Acute Myeloid Leukemia Calls for Action

Abstract

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 areas.

Post‐translational modifications of histones: Mechanisms, biological functions, and therapeutic targets

“…A better understanding of AML pathogenesis at the molecular level is important for guiding more precise treatment decisions in the future. The prospect of epigenetics in the research and treatment of leukemia has gradually gained focus 331–334 . The genetic heterogeneity of leukemia poses a therapeutic challenge.…”

“…The prospect of epigenetics in the research and treatment of leukemia has gradually gained focus. 331 , 332 , 333 , 334 The genetic heterogeneity of leukemia poses a therapeutic challenge. However, drugs targeting epigenetic mechanisms components are expected to be an integral part of leukemia treatment.…”

Research Progress for RNA Modifications in Physiological and Pathological Angiogenesis

“…2) Research on RNA modifications in angiogenesis. The crosstalk between protein modifications (PTMs) and DNA modifications in cancers has been well studied (Cedar and Bergman, 2009;Wu et al, 2019b;Hernandez-Valladares et al, 2019;Li et al, 2020b;Zhang et al, 2020), but RNA modification as an emerging epigenetic layer remains to be discovered. In a recent study for patients with CRC among different RNA modifications, the crosstalk between writers was introduced (Chen et al, 2021b).…”

Targeted and Immune-Based Therapies for Acute Myeloid Leukemia: Inflammatory Signaling and Multiple Post-Translational Modifications

“…Post-Translational Modification (PTM) crosstalk is a new promising research field that may be of great importance for dissection of aberrant signaling and consequently the development of new effective drugs for combating AML. The comprehensive review by Hernandez-Valladares et al [6] presents protocols for simultaneous enrichment of PTMs (phosphoproteome, methylproteome, glycoproteome and ubiquitinome), as well as providing bioinformatics tools for subsequent mass spectrometry-based data analysis of PTM crosstalk in AML.…”