Annotation Detail
Information
- Associated Genes
- FLT3
- Associated Variants
-
FLT3 p.Asp835Tyr (p.D835Y)
(
ENST00000241453.12 )
FLT3 p.Asp835Tyr (p.D835Y) ( ENST00000241453.12 ) - Associated Disease
- acute myeloid leukemia
- Source Database
- CIViC Evidence
- Description
- In an in-vitro study using an in vitro saturation mutagenesis assay, 4 residues with AC220 (quizartinib) resistance-conferring mutations in the kinase domain of FLT3-ITD were identified. Mutations at three of these amino acid positions conferred high degrees of in vitro AC220 resistance (based on proliferation and cell-based biochemical assays). Among these residues, two within the activation loop were found (D835, Y842). Pre-treatment and relapse samples of 8 patients (treated with AC220) with FLT3-ITD+ acute myeloid leukemia were analyzed. The activation loop mutation D835Y was detected in three cases, D835V in two, and D835F was identified in a single patient. Cross-resistance to sorafenib was identified in-vitro.
- Variant Origin
- somatic
- Variant Origin
- Somatic
- Evidence URL
- https://civic.genome.wustl.edu/links/evidence_items/1038
- Gene URL
- https://civic.genome.wustl.edu/links/genes/24
- Variant URL
- https://civic.genome.wustl.edu/links/variants/437
- Rating
- 4
- Evidence Type
- Predictive
- Disease
- Acute Myeloid Leukemia
- Evidence Direction
- Supports
- Drug
- Sorafenib,Quizartinib
- Evidence Level
- B
- Clinical Significance
- Resistance
- Pubmed
- 22504184
Drugs
| Drug Name | Sensitivity | Supported |
|---|---|---|
| Quizartinib | Resitance or Non-Reponse | true |
| Sorafenib | Resitance or Non-Reponse | true |