Annotation Detail
Information
- Associated Genes
- ABL1
- Associated Variants
- ABL1 p.Phe336Leu (p.F336L) ABL1 p.Phe336Leu (p.F336L)
- 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, patients with and without ABL1 mutation had comparable complete hematologic response (CHR), major cytogenetic response (MCyR), complete cytogenetic response (CCyR), and major molecular response (MMR). Out of 14 patients with F317L mutations, 1, 2, and 13 achieved CCyR, MCyR, and CHR to dasatinib monotherapy, respectively. Analyses by variant included patients with multiple kinase domain mutations. Despite high CHR in patients with the F317L variant, of the 63 variants considered, the authors associate T315I, F317L, and V299L with resistance or lower levels of response to dasatinib due to clinical resistance and low in vitro sensitivity. 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/6309
- Gene URL
- https://civic.genome.wustl.edu/links/genes/4
- Variant URL
- https://civic.genome.wustl.edu/links/variants/241
- Rating
- 3
- Evidence Type
- Predictive
- Disease
- Chronic Myeloid Leukemia
- Evidence Direction
- Supports
- Drug
- Dasatinib
- Evidence Level
- B
- Clinical Significance
- Resistance
- Pubmed
- 19779040
Drugs
| Drug Name | Sensitivity | Supported |
|---|---|---|
| Dasatinib | Resitance or Non-Reponse | true |