Protein signatures as potential surrogate biomarkers for stratification and prediction of treatment response in chronic myeloid leukemia patients

Abstract

There is unmet need for prediction of treatment response for chronic myeloid leukemia (CML) patients. The present study aims to identify disease-specific/disease-associated protein biomarkers detectable in bone marrow and peripheral blood for objective prediction of individual’s best treatment options and prognostic monitoring of CML patients. Bone marrow plasma (BMP) and peripheral blood plasma (PBP) samples from newly-diagnosed chronic-phase CML patients were subjected to expression-proteomics using quantitative two-dimensional gel electrophoresis (2-DE) and label-free liquid chromatography tandem mass spectrometry (LC-MS/MS). Analysis of 2-DE protein fingerprints preceding therapy commencement accurately predicts 13 individuals that achieved major molecular response (MMR) at 6 months from 12 subjects without MMR (No-MMR). Results were independently validated using LC-MS/MS analysis of BMP and PBP from patients that have more than 24 months followed-up. One hundred and sixty-four and 138 proteins with significant differential expression profiles were identified from PBP and BMP, respectively and only 54 proteins overlap between the two datasets. The protein panels also discriminates accurately patients that stay on imatinib treatment from patients ultimately needing alternative treatment. Among the identified proteins are TYRO3, a member of TAM family of receptor tyrosine kinases (RTKs), the S100A8, and MYC and all of which have been implicated in CML. Our findings indicate analyses of a panel of protein signatures is capable of objective prediction of molecular response and therapy choice for CML patients at diagnosis as ‘personalized-medicine-model’.

LC‑MS/MS proteomic analysis revealed novel associations of 37 proteins with T2DM and notable upregulation of immunoglobulins

“…The comparisons were made between the mean ± standard error of the mean values of the readings of each subset of samples, such as the depleted samples of T2DM males and female vs. the controls. The Progenesis QI V2.0/TransOmics Informatics (Waters Corporation) software was used to process and search the data using the principle of the search algorithm, as previously described (19,20). The data were filtered to show only statistically significant [P<0.05; analysis of variance (ANOVA) and post hoc Tukey's test] changes in protein concentration with maximum fold change (MFC) ≥1.5.…”

PD‐L1 promotes OCT4 and Nanog expression in breast cancer stem cells by sustaining PI3K/AKT pathway activation

“…Prior to expression proteomics analysis, total whole cell lysate protein extracts (100 lg) derived from MDA-MB-231 human breast cancer cell lines were subjected to in-solution tryptic digestion as previously described. 15 The protein identification was done using one-dimensional Nano Acquity liquid chromatography coupled with tandem mass spectrometry on Synapt G2 HDMS (Waters, Manchester, UK). The sample analysis was done on a Triazaic Nano source (Waters, Manchester, UK) and ionization in the positive ion mobility mode nanoESI as previously described.…”

“…The sample analysis was done on a Triazaic Nano source (Waters, Manchester, UK) and ionization in the positive ion mobility mode nanoESI as previously described. 15,16 The Progenesis QI for Proteomics version 2.0.5387 (Nonlinear Dynamics/ Waters, Manchester, UK) was used for all automated data processing and database searching using the Uniprot database (www.uniprot.org) for protein identification. The data were filtered to show only unambiguous protein identification using multiple parameters including expected molecular mass, percentage coverage, peptides count, unique peptides and confidence scores.…”

S100 Proteins in Acute Myeloid Leukemia

“…Finally, S100A8 appears to be negatively correlated with both treatment and sustained long-term major molecular response also in CML in a study with 37 patients and might therefore be a marker for aggressiveness, i.e., progression towards blast crisis [64] .…”