Fibroblast growth factor receptor signaling in pediatric B-cell precursor acute lymphoblastic leukemia
The FGF receptor signaling pathway is recurrently involved in the leukemogenic processes. Oncogenic fusions of FGFR1 with various fusion partners were described in myeloid proliferative neoplasms, and overexpression and mutations of FGFR3 are common in multiple myeloma. In addition, fibroblast growth factors are abundant in the bone marrow, and they were shown to enhance the survival of acute myeloid leukemia cells. Here we investigate the effect of FGFR stimulation on pediatric BCP-ALL cells in vitro, and search for mutations with deep targeted next-generation sequencing of mutational hotspots in FGFR1, FGFR2, and FGFR3. In 481 primary BCP-ALL cases, 28 samples from 19 unique relapsed BCPALL cases, and twelve BCP-ALL cell lines we found that mutations are rare (4/481 = 0.8%, 0/28 and 0/12) and do not affect codons which are frequently mutated in other malignancies. However, recombinant ligand FGF2 reduced the response to prednisolone in several BCP-ALL cell lines in vitro. We therefore conclude that FGFR signaling can contribute to prednisolone resistance in BCP-ALL cells, but that activating mutations in this receptor tyrosine kinase family are very rare.
|Persistent URL||dx.doi.org/10.1038/s41598-018-38169-z, hdl.handle.net/1765/115188|
Jerchel, I.S, Hoogkamer, A.Q, Ariës, I.M.A.A, Boer, J.M, Besselink, N, Koudijs, M.J, … den Boer, M.L. (2019). Fibroblast growth factor receptor signaling in pediatric B-cell precursor acute lymphoblastic leukemia. Scientific Reports, 9. doi:10.1038/s41598-018-38169-z