title: Cerebrospinal fluid proteomics in children during induction for acute lymphoblastic leukemia: A pilot study.
abstract: BACKGROUND
  Thrombosis in patients with acute lymphocytic leukemia (ALL) can develop after treatment with L-asparaginase (asp) and is often localized to the central nervous system (CNS). We hypothesize that changes in the cerebrospinal fluid (CSF) proteome will occur after asp therapy and will anticipate CNS clots.
  
  
  METHODS
  Five newly diagnosed patients, ages 1-11 years, with ALL (n = 4) or lymphoblastic lymphoma (LL) (n = 1) underwent serial lumbar punctures during induction. CSF was depleted of abundant plasma proteins and analyzed by gel-free, label-free quantitative proteomics.
  
  
  RESULTS
  More than 600 proteins were quantified across all CSF samples. In four subjects, the expression of proteins involved in coagulation such as protein C Inhibitor (SERPINA5) and heparin cofactor II (SERPIND1) changed over the course of asp therapy. Antithrombin III (ATIII) and plasminogen (PLMN) levels were shown to have decreased expression over time in one child who developed a CNS thrombosis, compared to other subjects.
  
  
  CONCLUSIONS
  CSF proteomics is feasible and reproducible in ALL and LL. CSF ATIII and PLMN should be further investigated as predictive markers of CNS thrombosis.
authors: Division of Pediatric Hematology/Oncology, University of North Carolina, Chapel Hill, North Carolina.
authors: Ginna M
authors: GM
authors: Priola
authors: Pulmonary, Allergy and Critical Care Medicine, Duke University Medical Center, Durham, North Carolina.|Proteomics and Metabolomics Shared Resource, Duke University Medical Center, Durham, North Carolina.
authors: Matthew W
authors: MW
authors: Foster
authors: Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina.
authors: Allison M
authors: AM
authors: Deal
authors: Proteomics and Metabolomics Shared Resource, Duke University Medical Center, Durham, North Carolina.
authors: Brenna M
authors: BM
authors: Richardson
authors: Proteomics and Metabolomics Shared Resource, Duke University Medical Center, Durham, North Carolina.
authors: J Will
authors: JW
authors: Thompson
authors: Division of Pediatric Hematology/Oncology, University of North Carolina, Chapel Hill, North Carolina.|Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina.
authors: Julie
authors: J
authors: Blatt
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D001927:Brain Diseases / Q000134:cerebrospinal fluid* / Q000209:etiology; D002648:Child; D002675:Child, Preschool; D002853:Chromatography, Liquid; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D010865:Pilot Projects; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000134:cerebrospinal fluid* / Q000150:complications; D011446:Prospective Studies; D040901:Proteomics / Q000379:methods*; D053719:Tandem Mass Spectrometry; D013927:Thrombosis / Q000134:cerebrospinal fluid* / Q000209:etiology; D055815:Young Adult
chemical_list: D015415:Biomarkers
keywords: ALL; CSF; asparaginase; proteomics; thrombosis