Identification of Protein Biomarker Signatures for Acute Myeloid Leukemia (AML) Using Both Nontargeted and Targeted Approaches

Abstract

Acute myeloid leukemia (AML) is characterized by an increasing number of clonal myeloid blast cells which are incapable of differentiating into mature leukocytes. AML risk stratification is based on genetic background, which also serves as a means to identify the optimal treatment of individual patients. However, constant refinements are needed, and the inclusion of significant measurements, based on the various omics approaches that are currently available to researchers/clinicians, have the potential to increase overall accuracy with respect to patient management. Using both nontargeted (label-free mass spectrometry) and targeted (multiplex immunoassays) proteomics, a range of proteins were found to be significantly changed in AML patients with different genetic backgrounds. The inclusion of validated proteomic biomarker panels could be an important factor in the prognostic classification of AML patients. The ability to measure both cellular and secreted analytes, at diagnosis and during the course of treatment, has advantages in identifying transforming biological mechanisms in patients, assisting important clinical management decisions.

Proteogenomic analysis of acute myeloid leukemia associates relapsed disease with reprogrammed energy metabolism both in adults and children

“…A few studies have performed global proteomics and phosphoproteomics on AML patient material (e.g., [9][10][11][12][13][14][15][16][17]). The studies carried out thus far mainly served to identify diagnostic or prognostic markers, or to investigate the efficacy of novel treatments.…”

Big data and single‐cell sequencing in acute myeloid leukemia research

“…1 Additionally, growing interest surrounds the exploration of proteomic and metabolomic signatures in AML and their interplay with distinct genomic profiles. [42][43][44] Notably, within a single AML sample, subpopulations may exhibit genetic, phenotypic, and epigenetic variations, collectively contributing to the initiation, progression, and evolution of AML. 1 Alongside studies on human AML samples, mouse models have emerged as valuable tools for validating the impact of diverse genetic and epigenetic abnormalities on AML development and progression, as well as investigating clonal evolution.…”

“…Extensive investigations of genetic, epigenetic, transcriptomic, and phenotypic profiles of AML samples have illuminated the profound complexity and diversity of this disease, surpassing previous notions 1 . Additionally, growing interest surrounds the exploration of proteomic and metabolomic signatures in AML and their interplay with distinct genomic profiles 42–44 . Notably, within a single AML sample, subpopulations may exhibit genetic, phenotypic, and epigenetic variations, collectively contributing to the initiation, progression, and evolution of AML 1 …”

Role of Biomarkers in the Management of Acute Myeloid Leukemia

“…Another proposed category of biomarkers is proteomic biomarkers. Dowling et al collected bone marrow samples from AML patients with favorable, intermediate, and unfavorable risk AML, and compared protein expression by mass spectrometry [ 104 ]. They found many significant differences between the different groups, such as increased proteins associated with metabolic pathways and biosynthesis of amino acids in the unfavorable group compared to the favorable risk group.…”