4 years ago

Identification of putative biomarkers for leptomeningeal invasion in B-cell non-Hodgkin lymphoma by NMR metabolomics

Carlos Fonseca, Gonçalo Graça, Joana Desterro, Joana Sousa, Tânia Carvalho, Margarida Silveira, Jacinta Serpa, Luís G. Gonçalves, Maria G. da Silva



B-cell non-Hodgkin lymphoma (B-NHL) is the most common hematological malignancy and different genetic alterations are frequently detected in transformed B lymphocytes. Within this heterogeneous disease, certain aggressive subgroups have an increased risk of central nervous system (CNS) involvement at diagnosis and/or relapse, resulting in parenchymal or leptomeningeal infiltration (LI) in 5–15% of cases. The current sensitivity limitations of cerebrospinal fluid (CSF) cytology and contrast-enhanced MRI for CNS involvement, mainly at early stages, motivates the search for alternative diagnostic methods.


Here we aim at using untargeted 1H-NMR metabolomics to identify putative biomarkers for LI in B-NHL patients.


CSF and peripheral blood samples were obtained from B-NHL patients with a positive (n = 7, LI group) or negative LI diagnostic (n = 13, control group). For seven patients, CSF samples were collected during the course of intrathecal chemotherapy, making it possible to assess the patient´s response to treatment. 1H-NMR spectra were acquired and statistical multivariate and univariate analysis were performed to identify significant alterations.


Significant metabolite differences were found between LI and control groups in CSF, but not in serum. A predictive PLS-DA cross-validated model identified significant pool changes in glycine, alanine, pyruvate, acetylcarnitine, carnitine, and phenylalanine. Additionally, increments in protein signals were detected in the LI group. Significantly, the PLS-DA model predicted correctly all samples obtained from the group of patients in remission during LI treatment.


The results show that the CSF NMR-metabolomics approach is a promising complementary method in clinical diagnosis and treatment follow-up of LI in B-NHL patients.

Publisher URL: https://link.springer.com/article/10.1007/s11306-017-1269-9

DOI: 10.1007/s11306-017-1269-9

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.