Annotation Detail

Information
Associated Genes
ABL1
Associated Variants
ABL1 p.Val318Leu (p.V318L) ( ENST00000318560.6, ENST00000372348.9 )
ABL1 p.Val318Leu (p.V318L) ( ENST00000318560.6, ENST00000372348.9 )
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, major cytogenetic response, complete cytogenetic response (CCyR), and major molecular response. There was 1 patient with a V299L mutation who did not achieved CCyR with dasatinib monotherapy. Analyses by variant included patients with multiple kinase domain mutations. Of the 63 variants considered, 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. They suggest considering alternative treatment options for patients with these variants.
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/4540
Gene URL
https://civic.genome.wustl.edu/links/genes/4
Variant URL
https://civic.genome.wustl.edu/links/variants/1231
Rating
1
Evidence Type
Predictive
Disease
Chronic Myeloid Leukemia
Evidence Direction
Supports
Drug
Dasatinib
Evidence Level
C
Clinical Significance
Resistance
Pubmed
19779040
Drugs
Drug NameSensitivitySupported
DasatinibResitance or Non-Reponsetrue