Abstract：
: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 BCP-ALL 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.
journal_name
Sci Repjournal_title
Scientific reportsauthors
Jerchel IS,Hoogkamer AQ,Ariës IM,Boer JM,Besselink NJM,Koudijs MJ,Pieters R,den Boer MLdoi
10.1038/s41598-018-38169-zsubject
Has Abstractpub_date
2019-02-12 00:00:00pages
1875issue
1issn
2045-2322pii
10.1038/s41598-018-38169-zjournal_volume
9pub_type
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pub_type： 杂志文章
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更新日期：2016-05-11 00:00:00
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pub_type： 临床试验,杂志文章
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journal_title：Scientific reports
pub_type： 临床试验,杂志文章,多中心研究
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更新日期：2016-02-01 00:00:00
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更新日期：2016-06-22 00:00:00
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journal_title：Scientific reports
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journal_title：Scientific reports
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更新日期：2017-04-06 00:00:00
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