Annotation Detail
Information
- Associated Genes
- NTRK3
- Associated Variants
- NTRK3 ETV6-NTRK3
- Associated Disease
- acute myeloid leukemia
- Source Database
- CIViC Evidence
- Description
- Two AML cell lines, IMS-M2 and M0-91, with the ETV6-NTRK3 fusion were treated with entrectinib. Sequencing of these cell lines found no other driver mutations in 265 other cancer genes suggesting the ETV6-NTRK3 fusion is the oncogenic driver. The IC50 for the IMS-M2 and M0-91 cell lines was 0.47 and 0.65 nmol/L, respectively. Mouse xenografts treated with entrectinib at 10 or 30 mg/kg had complete remission while treatment with 3 mg/kg caused significant reduction in tumor growth. Testing of the bone marrow of IMS-M2 xenografts after 3 weeks of treatment found no human CD45-positive cells in the 3, 10, and 30 mg/kg treatment groups; all vehicle treated mice had some human CD45-positive cells in their bone marrow. Zebrafish xenotransplantation of M0-91 cells were sensitive to entrectinib treatment.
- Variant Origin
- somatic
- Variant Origin
- Somatic
- Evidence URL
- https://civic.genome.wustl.edu/links/evidence_items/7994
- Gene URL
- https://civic.genome.wustl.edu/links/genes/3985
- Variant URL
- https://civic.genome.wustl.edu/links/variants/801
- Rating
- 3
- Evidence Type
- Predictive
- Disease
- Acute Myeloid Leukemia
- Evidence Direction
- Supports
- Drug
- Entrectinib
- Evidence Level
- D
- Clinical Significance
- Sensitivity/Response
- Pubmed
- 29237803
Drugs
| Drug Name | Sensitivity | Supported |
|---|---|---|
| Entrectinib | Sensitivity | true |