Table 2.
Liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based proteomics from recently (2017–2020) published studies of AML patient cohorts
| MS-Based Quantification | Sample Preparation Components | Clinical and Pathological Findings/Identified Marker(s) | Cohort Size a | Ref. |
|---|---|---|---|---|
| Label-free DDA | In-solution digestion, IP | Study on the protein tyrosine kinase-protein tyrosine phosphatase connections and effect on protein-phosphotyrosine signaling networks | 12 | [80] |
| Label-free DDA | FACS, in-solution digestion, high pH RP-fractionation | Altered expression of leukemia-enriched plasma membrane proteins on distinct AML subclones. Some of the proteins (e.g., IL3RA, TIM3, CD44, CD96, CD47, CD32, IL2RA, CD99, and CLEC12A) have been previously identified by other non-MS-based technologies | 42 | [81] |
| Label-free DDA | FASP | The constitutive release of mediators from primary AML differ from the intracellular protein levels | 19 | [82] |
| Label-free DDA, SRM | 2D-DIGE, IMAC | Phosphoprotein profiles reveal blast differentiation and cytogenic risk stratification | 62 | [83] |
| Label-free DDA | FASP | Patient subsets with high constitutive cytokine release levels show high expression of proteins involved in intracellular signaling interacting with integrins, RAC1, and SYK. AML cells with low release show high expression of transcriptional regulators | 16 | [84] |
| Label-free DDA | FASP | Strong antiproliferative and proapoptotic effects of metabolic pathways inhibitors on AML patient cells | 14 | [48] |
| Super-SILAC DDA | FASP, mixed-mode fractionation, IMAC | Higher phosphorylation of transcription regulators decreased cytokine release and increased integrin expression on cells from AML patients with high constitutive activation of the PI3K-AKT-mTOR signaling pathway | 20 | [85] |
| Super-SILAC DDA | FASP, mixed-mode fractionation, IMAC | Transcription factors and proteins involved in mRNA splicing are highly expressed in AML cells with self-renewal capacity | 15 | [86] |
| Super-SILAC DDA | FASP, mixed-mode fractionation, IMAC | Enhanced phosphorylation and activation of the PI3K-AKT-mTOR pathway by insulin is coupled to reduced antiproliferative effects of metabolic inhibitors in AML patient subsets | 14 | [68] |
| Super-SILAC DDA | FASP, mixed-mode fractionation, IMAC | High expression of RNA processing proteins, low expression of V-ATPase proteins, and higher activity of CSK2 and CDKs could help predict chemoresistant AML relapse | 41 | [46] |
| Super-SILAC DDA | FASP, mixed-mode fractionation, IMAC | High expression of mitochondrial ribosomal subunit proteins, RNA processing proteins, DNA repair proteins, and high activity of CDKs at AML relapse | 14 b | [47] |
| TMT DDA | FACS, LSCs engraftment, in-solution digestion, high pH RP-fractionation | Characterization of the expression of cell adhesion molecules, proteins of the oxidative phosphorylation process, and spliceosome factors in LSCs | 18 c | [87] |
| TMT DDA | FACS, LSCs engraftment, in-solution digestion, high pH RP-fractionation | BCAT1 is enriched in LSCs and links BCAA metabolism to epigenomic and post-translational HIF1α regulation via αKG-dependent dioxygenase | 18 c | [88] |
| TMT DDA | FACS, membrane, and cytosol isolation, in-solution digestion | Protein modification and cytoskeleton reorganization proteins showed an altered abundance in the proteome of leukemic progenitor cells | 5 | [89] |
| iTRAQ DDA | Nuclear isolation, in-solution digestion, high-pH RP-fractionation | Over-expression of nuclear S100A4 in AML cells. Nuclear S100A4 is crucial for AML survival | 15 | [90] |
a Cohort size is expressed as the number of AML patients in the study cohort; b 14: the number here represents 14 paired samples (diagnosis/relapse) from seven patients; c 18: the number here represents 18 AML populations from 6 patients; TMT: Tandem mass tag; LSCs: Leukemia stem cells; DDA: Data-dependent acquisition; IP: Immunoprecipitation; FACS: Fluorescence-activated cell sorting; RP: Reversed-phase; IL3RA: Interleukin-3 receptor subunit alpha; TIM3: T-cell immunoglobulin mucin receptor 3; CD: Cluster of differentiation; IL2RA: Interleukin-2 receptor subunit alpha; CLEC12A: C-type lectin domain family 12 member A; FASP: Filter-aided sample preparation; SRM: Selective reaction monitoring; DIGE: Difference gel electrophoresis; IMAC: Immobilized metal affinity chromatography; RAC1: Ras-related C3 botulinum toxin substrate 1; SYK: Tyrosine-protein kinase syk; SILAC: Stable isotope labeling with amino acids in cell culture; Mixed-mode fractionation: polystyrenedivinylbenzene reversed phase sulfonate, SDB-RPS; CSK2: Casein kinase 2; CDK: Cyclin-dependent kinase; BCAT1: BCAA transaminase 1; BCAA: Branched-chain amino acid; HIF1α: Hypoxia-inducible factor 1-alpha; KG: Ketoglutarate; iTRAQ: Isobaric tag for relative and absolute quantitation.