Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Oct;15(4):511-516.
doi: 10.3988/jcn.2019.15.4.511.

Prediction of Chemotherapy-Induced Peripheral Neuropathy in Patients with Lymphoma and Myeloma: the Roles of Brain-Derived Neurotropic Factor Protein Levels and A Gene Polymorphism

David Azoulay  1   2 , Sami Giryes  3 , Roni Nasser  3 , Rivka Sharon  1 , Netanel A Horowitz  3   4
Affiliations

Prediction of Chemotherapy-Induced Peripheral Neuropathy in Patients with Lymphoma and Myeloma: the Roles of Brain-Derived Neurotropic Factor Protein Levels and A Gene Polymorphism

David Azoulay et al. J Clin Neurol. 2019 Oct.

Abstract

Background and purpose: Brain-derived neurotrophic factor (BDNF) is a neuronal growth factor that plays an essential role in the maintenance of the nervous system. We have evaluated the peripheral blood protein levels of BDNF and the valine-to-methionine substitution at codon 66 (Val66Met) single-nucleotide polymorphism (SNP) as potential biomarkers for the early recognition of chemotherapy-induced peripheral neuropathy (CIPN) in non-Hodgkin lymphoma and multiple myeloma patients.

Methods: CIPN was assessed in 45 patients at the diagnosis and during vincristine or bortezomib-based therapy using objective [reduced version of the Total Neuropathy Score (TNSr)] and subjective (FACT-GOG-NTx) tools. Depression was assessed using the Patient Health Questionnaire-9 (PHQ-9) questionnaire. BDNF protein levels and the Val66Met SNP were determined using ELISA and Sanger sequencing.

Results: The pretreatment BDNF protein level was inversely correlated with the maximum TNSr, FACT-GOG-NTx, and PHQ-9 scores in both genotypes. BDNF patients with the Val/Val genotype demonstrated significantly higher maximum FACT-GOG-NTx and PHQ-9 scores than those with the Val/Met and Met/Met genotypes (Met-BNDF carriers). Correlations between PHQ-9 and TNSr score were found only in Met-BDNF carriers, suggesting that peripheral neuropathy and depression coincide in Met-BDNF carriers.

Conclusions: Determining the BDNF protein levels before initiating chemotherapy might be a useful tool for CIPN risk assessment and preemptive dose modification. The present data should be validated in larger studies that include other neurotoxic agents.

Keywords: BDNF; Val66Met single-nucleotide polymorphism; chemotherapy-induced peripheral neuropathy; multiple myeloma; non-Hodgkin lymphoma.

PubMed Disclaimer

Conflict of interest statement

The authors have no potential conflicts of interest to disclose.

Figures

Fig. 1
Fig. 1. Correlations between the pretreatment BDNF level and the objective symptoms (A), subjective symptoms (B), and depression (C) in CIPN patients. The graphs include linear regression lines for the relationships between pretreatment BDNF levels and the maximum TNSr, FACT-GOG-NTx, and PHQ-9 scores. BDNF: brain-derived neurotrophic factor, CIPN: chemotherapy-induced peripheral neuropathy, FACT-GOG-NTx: Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity, PHQ-9: Patient Health Questionnaire-9, TNSr: reduced version of the Total Neuropathy Score.
Fig. 2
Fig. 2. Baseline and maximum FACT-GOG-NTx scores (A) and PHQ-9 scores in Val-BDNF and Met-BDNF patients (B). Data are mean and SEM values. *p<0.05, †p<0.01. BDNF: brain-derived neurotrophic factor, FACT-GOG-NTx: Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity, PHQ-9: Patient Health Questionnaire-9.
See this image and copyright information in PMC

References

    1. Rocamora N, García-Ladona FJ, Palacios JM, Mengod G. Differential expression of brain-derived neurotrophic factor, neurotrophin-3, and low-affinity nerve growth factor receptor during the postnatal development of the rat cerebellar system. Brain Res Mol Brain Res. 1993;17:1–8. - PubMed
    1. Lipsky RH, Marini AM. Brain-derived neurotrophic factor in neuronal survival and behavior-related plasticity. Ann N Y Acad Sci. 2007;1122:130–143. - PubMed
    1. Novikova L, Novikov L, Kellerth JO. Brain-derived neurotrophic factor reduces necrotic zone and supports neuronal survival after spinal cord hemisection in adult rats. Neurosci Lett. 1996;220:203–206. - PubMed
    1. Egan MF, Kojima M, Callicott JH, Goldberg TE, Kolachana BS, Bertolino A, et al. The BDNF val66met polymorphism affects activitydependent secretion of BDNF and human memory and hippocampal function. Cell. 2003;112:257–269. - PubMed
    1. Białecka M, Kurzawski M, Roszmann A, Robowski P, Sitek EJ, Honczarenko K, et al. BDNF G196A (Val66Met) polymorphism associated with cognitive impairment in Parkinson's disease. Neurosci Lett. 2014;561:86–90. - PubMed