BDNF belongs to the nurse-like cell secretome and supports survival of B chronic lymphocytic leukemia cells

Sci Rep. 2020 Jul 28;10(1):12572. doi: 10.1038/s41598-020-69307-1.


Evading apoptosis and sustained survival signaling pathways are two central hallmarks of B-cell chronic lymphocytic leukemia (B-CLL) cells. In this regard, nurse-like cells (NLC), the monocyte-derived type 2 macrophages, deliver stimulatory signals via B-cell activating factor (BAFF), a proliferation-inducing ligand (APRIL), and the C-X-C Motif Chemokine Ligand 12 (CXCL12). Previously, we demonstrated that brain-derived neurotrophic factor (BDNF) protects B-CLL cells from spontaneous apoptosis by activating the oncogenic complex NTSR2-TrkB (neurotensin receptor 2-tropomyosin-related kinase receptor B), only overexpressed in B-CLL cells, inducing anti-apoptotic protein Bcl-2 (B-cell lymphoma 2) expression and Src kinase survival signaling pathways. Herein, we demonstrate that BDNF belongs to the NLC secretome and promotes B-CLL survival. This was demonstrated in primary B-CLL co-cultured with their autologous NLC, compared to B-CLL cells cultured alone. Inhibition of BDNF in co-cultures, enhances B-CLL apoptosis, whereas its exogenous recombinant activates pro-survival pathways in B-CLL cultured alone (i.e. Src activation and Bcl-2 expression), at a higher level than those obtained by the exogenous recombinant cytokines BAFF, APRIL and CXCL12, the known pro-survival cytokines secreted by NLC. Together, these results showed that BDNF release from NLC trigger B-CLL survival. Blocking BDNF would support research strategies against pro-survival cytokines to limit sustained B-CLL cell survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • B-Cell Activating Factor / genetics
  • B-Cell Activating Factor / metabolism
  • B-Lymphocytes / cytology
  • B-Lymphocytes / metabolism
  • Biological Transport
  • Brain-Derived Neurotrophic Factor / genetics
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / genetics
  • Leukemia, Lymphocytic, Chronic, B-Cell / metabolism*
  • Leukemia, Lymphocytic, Chronic, B-Cell / physiopathology
  • Macrophages / metabolism*
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Monocytes / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Receptor, trkB / genetics
  • Receptor, trkB / metabolism
  • Receptors, Neurotensin / genetics
  • Receptors, Neurotensin / metabolism
  • Signal Transduction


  • B-Cell Activating Factor
  • BCL2 protein, human
  • Brain-Derived Neurotrophic Factor
  • Membrane Glycoproteins
  • NTSR2 protein, human
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Neurotensin
  • Receptor, trkB
  • tropomyosin-related kinase-B, human