Annotation Detail
Information
- Associated Genes
- ABL1
- Associated Variants
- ABL1 p.Glu274Lys (p.E274K) ABL1 p.Glu274Lys (p.E274K)
- Associated Disease
- chronic myeloid leukemia
- Source Database
- CIViC Evidence
- Description
- In an in vitro study, stochastic mutations in the ABL1 region of a stably expressed p210 BCR-ABL fusion were generated in Ba/F3 cell lines from five independently derived, mutagenized libraries. Dasatinib resistant subclones were identified using 50 nM dasatinib in liquid culture. 201 individual clones were identified representing 10 different mutations at 6 different residues. 4 of these clones had E255K mutations. To validate resistance to dasatinib, a Ba/F3 cell line stably expressing the E255K mutation in the ABL1 region of the BCR-ABL fusion was generated. The E255K variants was associated with higher dasatinib IC50 of 13 nM vs 1.34 nM in wildtype and higher imatinib IC50 of 8,400 nM vs 323 nM in wildtype as determined by dose response curves.
- Variant Origin
- somatic
- Variant Origin
- Somatic
- Evidence URL
- https://civic.genome.wustl.edu/links/evidence_items/6214
- Gene URL
- https://civic.genome.wustl.edu/links/genes/4
- Variant URL
- https://civic.genome.wustl.edu/links/variants/3
- Rating
- 3
- Evidence Type
- Predictive
- Disease
- Chronic Myeloid Leukemia
- Evidence Direction
- Supports
- Drug
- Imatinib Mesylate,Dasatinib
- Evidence Level
- D
- Clinical Significance
- Resistance
- Pubmed
- 15705718
Drugs
| Drug Name | Sensitivity | Supported |
|---|---|---|
| Dasatinib | Resitance or Non-Reponse | true |
| Imatinib Mesylate | Resitance or Non-Reponse | true |