Elevated serum BDNF levels are associated with favorable outcome in CLL patients: Possible link to CXCR4 downregulation

David Azoulay; Yair Herishanu; Mika Shapiro; Yarden Brandshaft; Celia Suriu; Luiza Akria; Andrei Braester

doi:10.1016/j.exphem.2018.04.005

Elevated serum BDNF levels are associated with favorable outcome in CLL patients: Possible link to CXCR4 downregulation

Exp Hematol. 2018 Jul:63:17-21.e1. doi: 10.1016/j.exphem.2018.04.005. Epub 2018 Apr 26.

Authors

David Azoulay¹, Yair Herishanu², Mika Shapiro², Yarden Brandshaft³, Celia Suriu³, Luiza Akria³, Andrei Braester³

Affiliations

¹ Hematology Unit, Galilee Medical Center, Nahariya & Bar-Ilan University Faculty of Medicine Safed, Israel. Electronic address: davidA@gmc.gov.il.
² Department of Hematology, Sourasky Medical Center and Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
³ Hematology Unit, Galilee Medical Center, Nahariya & Bar-Ilan University Faculty of Medicine Safed, Israel.

PMID: 29705266
DOI: 10.1016/j.exphem.2018.04.005

Abstract

Increased chemokine C-X-C receptor 4 (CXCR4) expression is related to unfavorable outcome in chronic lymphocytic leukemia (CLL). Brain-derived neurotrophic factor (BDNF) is a neuronal growth factor that has been shown previously to interact with CXCR4 in neuronal cells. Here, we studied the in vitro effect of BDNF on CXCR4 expression and chemotaxis toward stromal derived factor-1 (SDF-1) in freshly isolated CLL cells. We also explored the correlations between serum BDNF levels in CLL patients and disease characteristics and clinical course. Incubation of CLL cells with recombinant BDNF (50 ng/mL) resulted in a downregulation of CXCR4 surface expression and atenuated chemotaxis toward SDF-1. Higher serum BDNF levels were associated with a mutated immunoglobulin heavy chain variable (IGHV) gene, an early clinical stage, and a stable clinical course. Our findings suggest that increased circulating blood BDNF may be associated with a favorable effect in CLL. However, the exact mechanism of this favorable effect should be investigated further.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Brain-Derived Neurotrophic Factor / blood*
Brain-Derived Neurotrophic Factor / genetics
Brain-Derived Neurotrophic Factor / pharmacokinetics
Brain-Derived Neurotrophic Factor / physiology
Chemokine CXCL12 / pharmacology
Chemotaxis / drug effects
Down-Regulation / drug effects
Gene Expression Regulation, Leukemic / drug effects
Gene Rearrangement, B-Lymphocyte, Heavy Chain
Genes, Immunoglobulin
Humans
Immunoglobulin Variable Region / genetics
Kaplan-Meier Estimate
Leukemia, Lymphocytic, Chronic, B-Cell / blood*
Leukemia, Lymphocytic, Chronic, B-Cell / genetics
Leukemia, Lymphocytic, Chronic, B-Cell / mortality
Leukemia, Lymphocytic, Chronic, B-Cell / pathology
Membrane Glycoproteins / biosynthesis
Membrane Glycoproteins / genetics
Neoplasm Proteins / biosynthesis
Neoplasm Proteins / blood*
Neoplasm Proteins / genetics
Neoplasm Proteins / physiology
Platelet Count
Prognosis
Receptor, trkB / biosynthesis
Receptor, trkB / genetics
Receptors, CXCR4 / biosynthesis*
Receptors, CXCR4 / genetics
Recombinant Proteins / pharmacology
Tumor Cells, Cultured

Substances

Brain-Derived Neurotrophic Factor
CXCL12 protein, human
CXCR4 protein, human
Chemokine CXCL12
Immunoglobulin Variable Region
Membrane Glycoproteins
Neoplasm Proteins
Receptors, CXCR4
Recombinant Proteins
BDNF protein, human
Receptor, trkB
tropomyosin-related kinase-B, human