Global Cell Proteome Profiling, Phospho-signaling and Quantitative Proteomics for Identification of New Biomarkers in Acute Myeloid Leukemia Patients

Abstract

The identification of protein biomarkers for acute myeloid leukemia (AML) that could find applications in AML diagnosis and prognosis, treatment and the selection for bone marrow transplant requires substantial comparative analyses of the proteomes from AML patients. In the past years, several studies have suggested some biomarkers for AML diagnosis or AML classification using methods for sample preparation with low proteome coverage and low resolution mass spectrometers. However, most of the studies did not follow up, confirm or validate their candidates with more patient samples. Current proteomics methods, new high resolution and fast mass spectrometers allow the identification and quantification of several thousands of proteins obtained from few tens of μg of AML cell lysate. Enrichment methods for posttranslational modifications (PTM), such as phosphorylation, can isolate several thousands of site-specific phosphorylated peptides from AML patient samples, which subsequently can be quantified with high confidence in new mass spectrometers. While recent reports aiming to propose proteomic or phosphoproteomic biomarkers on the studied AML patient samples have taken advantage of the technological progress, the access to large cohorts of AML patients to sample from and the availability of appropriate control samples still remain challenging.

Proteome and Phosphoproteome Changes Associated with Prognosis in Acute Myeloid Leukemia

“…Liquid chromatography tandem mass spectrometry (LC-MS/MS)-based proteomics or phosphoproteomics have been utilized for the subclassification of patients with non-APL variants of AML [23][24][25] and for the study of proteins released by apoptosis-resistant and sensitive primary AML cells [26]. Remarkable advances in the mass spectrometry technology over the past decades have provided equipment with optimized resolution, allowing high coverage characterizations of post-translation modifications (PTMs).…”

Proteome and phosphoproteome changes associated with prognosis in acute myeloid leukemia

“…[15][16][17][18][19][20] However, liquid chromatography tandem mass spectrometry (LC-MS/MS)-based proteomics or phosphoproteomics can also be used for subclassification of patients with non-APL variants of AML. [21][22][23][24][25][26] In the present study we therefore compared the proteome and phosphoproteome profiles of primary AML cells collected at the time of diagnosis for patients who later either became long-term leukemia-free survivors or suffered from chemoresistant relapse. Based on the proteomics and phosphoproteomics analysis of these two groups, we found common denominators in diagnostic samples which could be utilized for future treatments for patients that would later relapse.…”

Selecting Sample Preparation Workflows for Mass Spectrometry-Based Proteomic and Phosphoproteomic Analysis of Patient Samples with Acute Myeloid Leukemia

“…Specially, mass spectrometry (MS)-based proteomic studies on AML patient samples have been increasingly published in the past years. Most of them have been recently reviewed by another research group [8] and us [9]. Early MS-based proteomic studies on AML, which have mostly been carried out with two-dimensional electrophoresis (2DE)-based approaches combined with matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF)- or liquid chromatography (LC)-MS, resulted in a low number of quantified proteins compared to shotgun proteomics.…”