ArticleLeukemia2018
FGFR1 fusion kinase regulation of MYC expression drives development of stem cell leukemia/lymphoma syndrome.
Article in Leukemia, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 39 citations in OpenAlex.
- BCR-ABL1 Drives Transcriptional Reprogramming of Chronic Myeloid Leukemia Cells for Immune Evasion Through C/EBPβ.MedComm · 2026Article
- Article
- The FGF/FGFR/c-Myc axis as a promising therapeutic target in multiple myeloma.Journal of experimental & clinical cancer research : CR · 2024Review
- Myeloid/lymphoid neoplasms with eosinophilia and FGFR1 rearrangement t(8;13)(p11;q12): A case report and literature review.Oncology letters · 2024Article
- Biology and Therapeutic Properties of Mesenchymal Stem Cells in Leukemia.International journal of molecular sciences · 2024Review
- Genome-wide open reading frame profiling identifies fibroblast growth factor signaling as a driver of PD-L1 expression in head and neck squamous cell carcinoma.Oral oncology · 2023Article
- RHOA-regulated IGFBP2 promotes invasion and drives progression of BCR-ABL1 chronic myeloid leukemia.Haematologica · 2023Article
- Blockade of FGF2/FGFR2 partially overcomes bone marrow mesenchymal stromal cells mediated progression of T-cell acute lymphoblastic leukaemia.Cell death & disease · 2022Article
- A truncated derivative of FGFR1 kinase cooperates with FLT3 and KIT to transform hematopoietic stem cells in syndromic and de novo AML.Molecular cancer · 2022Article
- Identification of a novel HOOK3-FGFR1 fusion gene involved in activation of the NF-kappaB pathway.Cancer cell international · 2022Article
- Proteomic analysis reveals dual requirement for Grb2 and PLCγ1 interactions for BCR-FGFR1-Driven 8p11 cell proliferation.Oncotarget · 2022Article
- Mechanisms of resistance to FGFR1 inhibitors in FGFR1-driven leukemias and lymphomas: implications for optimized treatment.Cancer drug resistance (Alhambra, Calif.) · 2021Article
- Downregulation of PUMA underlies resistance to FGFR1 inhibitors in the stem cell leukemia/lymphoma syndrome.Cell death & disease · 2020Article
- Oncogenic fusion protein BCR-FGFR1 requires the breakpoint cluster region-mediated oligomerization and chaperonin Hsp90 for activation.Haematologica · 2020Article
- mRNA Expression of FGFR1 as Potential Marker for Predicting Prognosis of Surgical Resection of Small Cell Lung Cancer may be better than Protein Expression and Gene Amplification.Journal of Cancer · 2020Article
- Rac1/2 activation promotes FGFR1 driven leukemogenesis in stem cell leukemia/lymphoma syndrome.Haematologica · 2020Article
- DNA methyltransferase 1-mediated CpG methylation of the miR-150-5p promoter contributes to fibroblast growth factor receptor 1-driven leukemogenesis.The Journal of biological chemistry · 2019Article
- BCR: a promiscuous fusion partner in hematopoietic disorders.Oncotarget · 2019Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Oncogenic transformation of hematopoietic stem cells by chimeric fusion kinases causing constitutive activation of FGFR1 leads to a stem cell leukemia/lymphoma (SCLL) syndrome, accompanied by widespread dysregulation of gene activity. We now show that FGFR1 activation is associated with upregulation of MYC and pharmacological suppression of FGFR1 activation leads to downregulation of MYC and suppression of MYC target genes. Luciferase reporter assays demonstrate that FGFR1 can directly regulate MYC expression and this effect is enhanced in the presence of chimeric FGFR1 kinases. In SCLL cells, a truncated form of FGFR1 is generated by granzyme B cleavage of the chimeric kinases, producing a nucleus-restricted derivative that can bind MYC regulatory regions. Mutation of the granzyme B cleavage site prevents relocation to the nucleus but does not suppress MYC activation, suggesting additional mechanisms of MYC activation in the presence of cytoplasm-restricted chimeric kinases. We show that one of these mechanisms involves activating cytoplasmic STAT5, which upregulates MYC independent of the truncated FGFR1 kinase. Targeting MYC function using shRNA knockdown and 10054-F8 in SCLL cells leads to inhibition of cell proliferation and synergizes with the BGJ398 FGFR1 inhibitor, suggesting a combination therapy that could be used in the treatment of SCLL.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.