Journal
JOURNAL OF PROTEOME RESEARCH
Volume 19, Issue 7, Pages 2606-2616Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.jproteome.0c00291
Keywords
cerebrospinal fluid; central nervous system; dimethyl leucine (DiLeu) isobaric labeling; B-cell acute lymphoblastic leukemia; chemotherapy; protein dynamics
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Funding
- Clinical and Translational Science Award (CTSA) program [NIH NCATS UL1TR000427]
- National Institutes of Health (NIH) [RF1AG052324, R01DK071801, P41GM108538]
- NIH [NIH-NCRR S10RR029531]
- Office of the Vice Chancellor for Research and Graduate Education at the University of Wisconsin-Madison
- Wisconsin Alumni Research Foundation
- University of Wisconsin-Madison School of Pharmacy
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The use of mass spectrometry for protein identification and quantification in cerebrospinal fluid (CSF) is at the forefront of research efforts to identify and explore biomarkers for the early diagnosis and prognosis of neurologic disorders. Here we implemented a 4-plex N,N-dimethyl leucine (DiLeu) isobaric labeling strategy in a longitudinal study aiming to investigate protein dynamics in children with B-cell acute lymphoblastic leukemia (B-cell ALL) undergoing chemotherapy. The temporal profile of CSF proteome during chemotherapy treatment at weeks 5, 10-14, and 24-28 highlighted many differentially expressed proteins, such as neural cell adhesion molecule, neuronal growth regulator 1, and secretogranin-3, all of which play important roles in neurodegenerative diseases. A total of 63 proteins were significantly altered across all of the time points investigated. The most over-represented biological processes from gene ontology analysis included platelet degranulation, complement activation, cell adhesion, fibrinolysis, neuron projection, regeneration, and regulation of neuron death. We expect that results from this and future studies will provide a means to monitor neurotoxicity and develop strategies to prevent central nervous system injury in response to chemotherapy in children.
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