Fgf2-fgfr1 signaling regulates release of leukemia-protective exosomes from bone marrow stromal cells

Nathalie Javidi-Sharifi, Jacqueline Martinez, Isabel English, Sunil K. Joshi, Renata Scopim-Ribiero, David K. Edwards V, Anupriya Agarwal, Claudia Lopez, Danielle Jorgens, Jeffrey W. Tyner, Brian J. Druker, Elie Traer

Research output: Contribution to journalArticlepeer-review

39 Scopus citations


Protective signaling from the leukemia microenvironment leads to leukemia cell persistence, development of resistance, and disease relapse. Here, we demonstrate that fibroblast growth factor 2 (FGF2) from bone marrow stromal cells is secreted in exosomes, which are subsequently endocytosed by leukemia cells, and protect leukemia cells from tyrosine kinase inhibitors (TKIs). Expression of FGF2 and its receptor, FGFR1, are both increased in a subset of stromal cell lines and primary AML stroma; and increased FGF2/FGFR1 signaling is associated with increased exosome secretion. FGFR inhibition (or gene silencing) interrupts stromal autocrine growth and significantly decreases secretion of FGF2-containing exosomes, resulting in less stromal protection of leukemia cells. Likewise, Fgf2 -/- mice transplanted with retroviral BCR-ABL leukemia survive significantly longer than their +/+ counterparts when treated with TKI. Thus, inhibition of FGFR can modulate stromal function, reduce exosome secretion, and may be a therapeutic option to overcome resistance to TKIs.

Original languageEnglish (US)
Article numbere40033
StatePublished - Feb 2019

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)


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