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Pediatr Blood Cancer. 2015 Jul;62(7):1190-4. doi: 10.1002/pbc.25420. Epub 2015 Mar 23.

Cerebrospinal fluid proteomics in children during induction for acute lymphoblastic leukemia: A pilot study.

Author information

1
Division of Pediatric Hematology/Oncology, University of North Carolina, Chapel Hill, North Carolina.
2
Pulmonary, Allergy and Critical Care Medicine, Duke University Medical Center, Durham, North Carolina.
3
Proteomics and Metabolomics Shared Resource, Duke University Medical Center, Durham, North Carolina.
4
Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina.

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.

KEYWORDS:

ALL; CSF; asparaginase; proteomics; thrombosis

PMID:
25809122
DOI:
10.1002/pbc.25420
[Indexed for MEDLINE]

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