title: 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'.
authors: Proteomics Unit, Stem Cell and Tissue Re-Engineering Program, King Faisal Specialist Hospital and Research Centre, (KFSH&RC), Riyadh, 11211 Saudi Arabia.
authors: Ayodele A
authors: AA
authors: Alaiya
authors: Adult Hematology/HSCT Section, Oncology Center, King Faisal Specialist Hospital and Research Centre, (KFSH&RC), Riyadh, 11211 Saudi Arabia.
authors: Mahmoud
authors: M
authors: Aljurf
authors: Proteomics Unit, Stem Cell and Tissue Re-Engineering Program, King Faisal Specialist Hospital and Research Centre, (KFSH&RC), Riyadh, 11211 Saudi Arabia.
authors: Zakia
authors: Z
authors: Shinwari
authors: Adult Hematology/HSCT Section, Oncology Center, King Faisal Specialist Hospital and Research Centre, (KFSH&RC), Riyadh, 11211 Saudi Arabia.
authors: Fahad
authors: F
authors: Almohareb
authors: Adult Hematology/HSCT Section, Oncology Center, King Faisal Specialist Hospital and Research Centre, (KFSH&RC), Riyadh, 11211 Saudi Arabia.
authors: Hafiz
authors: H
authors: Malhan
authors: Adult Hematology/HSCT Section, Oncology Center, King Faisal Specialist Hospital and Research Centre, (KFSH&RC), Riyadh, 11211 Saudi Arabia.
authors: Hazzaa
authors: H
authors: Alzahrani
authors: Hematopathology Section, Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Centre, (KFSH&RC), Riyadh, 11211 Saudi Arabia.
authors: Tarek
authors: T
authors: Owaidah
authors: Waters U.K. Limited, Atlas Park, Simonsway, Manchester, M22 5PP, UK.
authors: Jonathan
authors: J
authors: Fox
authors: Adult Hematology/HSCT Section, Oncology Center, King Faisal Specialist Hospital and Research Centre, (KFSH&RC), Riyadh, 11211 Saudi Arabia.
authors: Fahad
authors: F
authors: Alsharif
authors: Adult Hematology/HSCT Section, Oncology Center, King Faisal Specialist Hospital and Research Centre, (KFSH&RC), Riyadh, 11211 Saudi Arabia.
authors: Said Y
authors: SY
authors: Mohamed
authors: Adult Hematology/HSCT Section, Oncology Center, King Faisal Specialist Hospital and Research Centre, (KFSH&RC), Riyadh, 11211 Saudi Arabia.
authors: Walid
authors: W
authors: Rasheed
authors: Adult Hematology/HSCT Section, Oncology Center, King Faisal Specialist Hospital and Research Centre, (KFSH&RC), Riyadh, 11211 Saudi Arabia.
authors: Ghuzayel
authors: G
authors: Aldawsari
authors: Adult Hematology/HSCT Section, Oncology Center, King Faisal Specialist Hospital and Research Centre, (KFSH&RC), Riyadh, 11211 Saudi Arabia.
authors: Amr
authors: A
authors: Hanbali
authors: Adult Hematology/HSCT Section, Oncology Center, King Faisal Specialist Hospital and Research Centre, (KFSH&RC), Riyadh, 11211 Saudi Arabia.
authors: Syed Osman
authors: SO
authors: Ahmed
authors: Adult Hematology/HSCT Section, Oncology Center, King Faisal Specialist Hospital and Research Centre, (KFSH&RC), Riyadh, 11211 Saudi Arabia.
authors: Naeem
authors: N
authors: Chaudhri
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood / Q000378:metabolism*; D001853:Bone Marrow / Q000378:metabolism; D040501:Calgranulin A / Q000097:blood / Q000378:metabolism; D002853:Chromatography, Liquid; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D040901:Proteomics / Q000379:methods*; D016271:Proto-Oncogene Proteins c-myc / Q000097:blood / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000097:blood / Q000378:metabolism; D053719:Tandem Mass Spectrometry; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D040501:Calgranulin A; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D020794:Receptor Protein-Tyrosine Kinases; C084944:TYRO3 protein, human