Annotation Detail
Information
- Associated Genes
- ABL1
- Associated Variants
-
ABL1 p.Leu267Arg (p.L267R)
(
ENST00000318560.6,
ENST00000372348.9 )
ABL1 p.Leu267Arg (p.L267R) ( ENST00000318560.6, ENST00000372348.9 ) - 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. 1 of these clones had an L248R mutation. To validate resistance to dasatinib, a Ba/F3 cell line stably expressing the L248R mutation in the ABL1 region of the BCR-ABL fusion was generated. The L248R variants was associated with higher dasatinib IC50 of 16 nM vs 1.34 nM in wildtype and higher imatinib IC50 of >10,000 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/6210
- Gene URL
- https://civic.genome.wustl.edu/links/genes/4
- Variant URL
- https://civic.genome.wustl.edu/links/variants/2340
- 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 |