Annotation Detail
Information
- Associated Genes
- ABL1
- Associated Variants
-
ABL1 MUTATION
ABL1 MUTATION - Associated Disease
- chronic myeloid leukemia
- Source Database
- CIViC Evidence
- Description
- This is a retrospective study of imatinib-resistant (n = 805) or -intolerant (n = 238), chronic myeloid leukemia (chronic-phase), patients with mutations in the BCR-ABL gene fusion kinase domain from the START-C, START-R, and CA180-034 trials. With dasatinib monotherapy, imatinib-resistant patients with and without ABL1 mutation had comparable complete hematologic response [CHR= 90% (345/384) vs. 93% (390/421)], major cytogenetic response [MCyR= 56% (211/384) vs. 58% (243/421)], complete cytogenetic response [CCyR= 43% (164/384) vs. 47% (196/421)], and major molecular response [MMR= 31% (115/367) vs. 36% (145/404)]. Of the 63 imatinib-resistant variants observed (see comment), the authors associate T315I, F317L, and V299L with resistance to dasatinib or lower levels of response due to clinical resistance and low in vitro sensitivity. However, F317L does have a high CHR. They suggest considering alternative treatment options for patients with these three variants.
- Variant Origin
- somatic
- Variant Origin
- Somatic
- Evidence URL
- https://civic.genome.wustl.edu/links/evidence_items/6311
- Gene URL
- https://civic.genome.wustl.edu/links/genes/4
- Variant URL
- https://civic.genome.wustl.edu/links/variants/2371
- Rating
- 3
- Evidence Type
- Predictive
- Disease
- Chronic Myeloid Leukemia
- Evidence Direction
- Does Not Support
- Drug
- Dasatinib
- Evidence Level
- B
- Clinical Significance
- Resistance
- Pubmed
- 19779040
Drugs
| Drug Name | Sensitivity | Supported |
|---|---|---|
| Dasatinib | Resitance or Non-Reponse | false |