title: Plasma proteomics in CML patients before and after initiation of tyrosine kinase inhibitor therapy reveals induced Th1 immunity and loss of angiogenic stimuli.
abstract: The simultaneous measurement of many proteins is now possible using multiplex assays. In this pilot study we investigated a total of 124 proteins in plasma from chronic myeloid leukemia (CML) patients with the purpose of identifying proteins that are differently expressed at diagnosis and after tyrosine kinase inhibitor (TKI) treatment initiation.
  
  
  
  Samples were taken from 14 CML patients at diagnosis and after three months of TKI treatment (imatinib or dasatinib). Samples were analyzed by Mesoscale Discovery, Myriad RBM MAP technology and Olink Proseek.
  
  
  
  Multiple plasma proteins were differentially expressed before and after initiation of TKI therapy. Protein patterns demonstrated a possible shift towards Th1-immunity and reduced angiogenic stimuli. Further, some plasma proteins were identified that can be of potential interest to study further for biologic, prognostic or therapeutic significance such as E-selectin, uPAR, growth hormone and carbonic anhydrase IX.
  
  
  
  Plasma proteomics seems feasible and useful in CML patients, both for studying patterns of protein expression and for identifying single proteins differentially expressed before and after treatment. Plasma proteomics may be useful to map disease activity and biological processes. Hence, plasma proteomics can be used to understand drug mechanisms and treatment responses in CML.
authors.affiliation: Dept. of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden; Dept. of Medical Sciences, Uppsala University, Uppsala, Sweden; Section of Hematology, Uppsala University Hospital, Uppsala, Sweden. Electronic address: stina.soderlund@igp.uu.se.
authors.forename: Stina
authors.initials: S
authors.lastname: Söderlund
authors.affiliation: Dept. of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Lisa
authors.initials: L
authors.lastname: Christiansson
authors.affiliation: Dept. of Statistics, Uppsala University, Uppsala, Sweden.
authors.forename: Inger
authors.initials: I
authors.lastname: Persson
authors.affiliation: Department of Hematology, St. Olav's Hospital, Trondheim, Norway; Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
authors.forename: Henrik
authors.initials: H
authors.lastname: Hjorth-Hansen
authors.affiliation: Department of Hematology, Oncology and Radiation Physics, Skåne University Hospital, Lund, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Richter
authors.affiliation: Dept. of Medical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Bengt
authors.initials: B
authors.lastname: Simonsson
authors.affiliation: Hematology Research Unit Helsinki, Department of Hematology, University of Helsinki and Helsinki University Central Hospital Comprehensive Cancer Center, Helsinki, Finland; Department of Clinical Chemistry, University of Helsinki, Helsinki, Finland.
authors.forename: Satu
authors.initials: S
authors.lastname: Mustjoki
authors.affiliation: Dept. of Medical Sciences, Uppsala University, Uppsala, Sweden; Section of Hematology, Uppsala University Hospital, Uppsala, Sweden.
authors.forename: Ulla
authors.initials: U
authors.lastname: Olsson-Strömberg
authors.affiliation: Dept. of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Angelica
authors.initials: A
authors.lastname: Loskog
mesh_terms: D000328:Adult; D000368:Aged; D001798:Blood Proteins / Q000032:analysis; D000069439:Dasatinib / Q000627:therapeutic use; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate / Q000627:therapeutic use; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D010865:Pilot Projects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D040901:Proteomics / Q000379:methods*; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology
chemical_list: D001798:Blood Proteins; D047428:Protein Kinase Inhibitors; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D000069439:Dasatinib
keywords: Angiogenesis; Chronic myeloid leukemia; Proteomics; Th1; Tyrosine kinase inhibitor