ArticleMolecular and cellular biology2000
Identification and characterization of an activating TrkA deletion mutation in acute myeloid leukemia.
Article in Molecular and cellular biology, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 2 of them syntheses that pooled it.
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Who cites it
43 citing papers in PubMed, 2 syntheses or guidelines pooled it, 115 citations in OpenAlex.
- Japanese Society of Medical Oncology/Japan Society of Clinical Oncology/Japanese Society of Pediatric Hematology/Oncology-led clinical recommendations on the diagnosis and use of tropomyosin receptor kinase inhibitors in adult and pediatric patients with neurotrophic receptor tyrosine kinase fusion-positive advanced solid tumors.International journal of clinical oncology · 2023Guideline
- Japan society of clinical oncology/Japanese society of medical oncology-led clinical recommendations on the diagnosis and use of tropomyosin receptor kinase inhibitors in adult and pediatric patients with neurotrophic receptor tyrosine kinase fusion-positive advanced solid tumors, cooperated by the Japanese society of pediatric hematology/oncology.International journal of clinical oncology · 2020Guideline
- NTRK fusion promotes tumor migration and invasion through epithelial-mesenchymal transition and closely interacts with ECM1 and NOVA1.BMC cancer · 2024Article
- Pyrazolo[1,5-Molecules (Basel, Switzerland) · 2024Review
- Selective type II TRK inhibitors overcome xDFG mutation mediated acquired resistance to the second-generation inhibitors selitrectinib and repotrectinib.Acta pharmaceutica Sinica. B · 2024Review
- NTRK amplification occurs frequently in pan-TRK immunopositive dedifferentiated liposarcomas.Pathology oncology research : POR · 2024Article
- Analysis of CD74 Occurrence in Oncogenic Fusion Proteins.International journal of molecular sciences · 2023Review
- TrkA Co-Receptors: The Janus Face of TrkA?Cancers · 2023Review
- Research Progress on Small Molecules Inhibitors Targeting TRK Kinases.Current medicinal chemistry · 2023Article
- NTRK Gene Fusion Detection in Atypical Spitz Tumors.International journal of molecular sciences · 2021Article
- Targeted activity of the small molecule kinase inhibitor Pz-1 towards RET and TRK kinases.Scientific reports · 2021Article
- Development of small-molecule tropomyosin receptor kinase (TRK) inhibitors forActa pharmaceutica Sinica. B · 2021Review
- Discovery and characterization of targetable NTRK point mutations in hematologic neoplasms.Blood · 2020Article
- Review
- Review
- The TP53 Apoptotic Network Is a Primary Mediator of Resistance to BCL2 Inhibition in AML Cells.Cancer discovery · 2019Article
- Detection of Tumor NTRK Gene Fusions to Identify Patients Who May Benefit from Tyrosine Kinase (TRK) Inhibitor Therapy.The Journal of molecular diagnostics : JMD · 2019Review
- Insights into Current Tropomyosin Receptor Kinase (TRK) Inhibitors: Development and Clinical Application.Journal of medicinal chemistry · 2019Article
- NTRK fusion-positive cancers and TRK inhibitor therapy.Nature reviews. Clinical oncology · 2018Review
- Oncogenic TRK fusions are amenable to inhibition in hematologic malignancies.The Journal of clinical investigation · 2018Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
In this study, we utilized retroviral transfer of cDNA libraries in order to identify oncogenes that are expressed in acute myeloid leukemia (AML). From screens using two different cell types as targets for cellular transformation, a single cDNA encoding a variant of the TrkA protooncogene was isolated. The protein product of this protooncogene, TrkA, is a receptor tyrosine kinase for nerve growth factor. The isolated transforming cDNA encoded a TrkA protein that contains a 75-amino-acid deletion in the extracellular domain of the receptor and was named DeltaTrkA. DeltaTrkA readily transformed fibroblast and epithelial cell lines. The deletion resulted in activation of the tyrosine kinase domain leading to constitutive tyrosine phosphorylation of the protein. Expression of DeltaTrkA in cells led to the constitutive activation of intracellular signaling pathways that include Ras, extracellular signal-regulated kinase/mitogen-activated protein kinase, and Akt. Importantly, DeltaTrkA altered the apoptotic and growth properties of 32D myeloid progenitor cells, suggesting DeltaTrkA may have contributed to the development and/or maintenance of the myeloid leukemia from which it was isolated. Unlike Bcr-Abl, expression of DeltaTrkA did not activate Stat5 in these cells. We have detected expression of DeltaTrkA in the original AML sample by reverse transcriptase PCR and by Western blot analysis. While previous TrkA mutations identified from human tumors involved fusion to other proteins, this report is the initial demonstration that deletions within TrkA may play a role in human cancers. Finally, this report is the first to indicate mutations in TrkA may contribute to leukemogenesis.
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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.