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

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

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4 Citations (Scopus)


Introduction: 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. Objectives: Here we aim at using untargeted 1H-NMR metabolomics to identify putative biomarkers for LI in B-NHL patients. Methods: 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. Results: 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. Conclusions: 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.

Original languageEnglish
Article number136
Issue number11
Publication statusPublished - 1 Nov 2017


  • B cell non-Hodgkin lymphoma
  • Cerebrospinal fluid
  • Leptomeningeal infiltration
  • NMR metabolomics
  • Serum


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