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

Alaiya,Ayodele  A.; Aljurf,Mahmoud; Shinwari,Zakia; Almohareb,Fahad; Malhan,Hafiz; Alzahrani,Hazzaa; Owaidah,Tarek; Fox,Jonathan; Alsharif,Fahad; Mohamed,Said  Y.; Rasheed,Walid; Aldawsari,Ghuzayel; Hanbali,Amr; Ahmed,Syed  Osman; Chaudhri,Naeem

doi:10.3892/ijo.2016.3618

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

Authors:
- Ayodele A. Alaiya
- Mahmoud Aljurf
- Zakia Shinwari
- Fahad Almohareb
- Hafiz Malhan
- Hazzaa Alzahrani
- Tarek Owaidah
- Jonathan Fox
- Fahad Alsharif
- Said Y. Mohamed
- Walid Rasheed
- Ghuzayel Aldawsari
- Amr Hanbali
- Syed Osman Ahmed
- Naeem Chaudhri
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Affiliations: Proteomics Unit, Stem Cell and Tissue Re-Engineering Program, King Faisal Specialist Hospital and Research Centre, (KFSH&RC), Riyadh, 11211 Saudi Arabia, Adult Hematology/HSCT Section, Oncology Center, King Faisal Specialist Hospital and Research Centre, (KFSH&RC), Riyadh, 11211 Saudi Arabia, Hematopathology Section, Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Centre, (KFSH&RC), Riyadh, 11211 Saudi Arabia, Waters U.K. Limited, Atlas Park, Simonsway, Manchester, M22 5PP, UK
Published online on: July 7, 2016 https://doi.org/10.3892/ijo.2016.3618
Pages: 913-933
Copyright: © Alaiya et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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’.

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