Annotation Detail
Information
- Associated Genes
- ABL1
- Associated Variants
-
ABL1 p.Tyr272His (p.Y272H)
(
ENST00000318560.6,
ENST00000372348.9 )
ABL1 p.Tyr272His (p.Y272H) ( ENST00000318560.6, ENST00000372348.9 ) - Associated Disease
- chronic myeloid leukemia
- Source Database
- CIViC Evidence
- Description
- In an in vitro study, a Ba/F3-p210BCR-ABL1 cell line was ENU-mutated and exposed to graded concentrations of imatinib, nilotinib or dasatinib to identify resistance mutations. The Y253H mutation in the ABL1 portion of the BCR-ABL1 fusion protein was associated with resistance to 50nM nilotinib (14 clones recovered, ~30% of viable clones in this treatment), 500nM nilotinib (50 clones, ~63%), and 16 nM imatinib (16 clones; ~48%). Resistant clones were also found at 2, 4, and 8 μM imatinib. In a review of 20 publications, this mutation was described in imatinib resistant patients.
- Variant Origin
- somatic
- Variant Origin
- Somatic
- Evidence URL
- https://civic.genome.wustl.edu/links/evidence_items/2654
- Gene URL
- https://civic.genome.wustl.edu/links/genes/4
- Variant URL
- https://civic.genome.wustl.edu/links/variants/1025
- Rating
- 3
- Evidence Type
- Predictive
- Disease
- Chronic Myeloid Leukemia
- Evidence Direction
- Supports
- Drug
- Nilotinib,Imatinib Mesylate
- Evidence Level
- D
- Clinical Significance
- Resistance
- Pubmed
- 16772610
Drugs
| Drug Name | Sensitivity | Supported |
|---|---|---|
| Imatinib Mesylate | Resitance or Non-Reponse | true |
| Nilotinib | Resitance or Non-Reponse | true |