Annotation Detail

Information
Associated Genes
ABL1
Associated Variants
ABL1 p.Thr334Ile (p.T334I) ABL1 p.Thr334Ile (p.T334I)
Associated Disease
chronic myeloid leukemia
Source Database
CIViC Evidence
Description
In an in vitro study, stochastic mutations were introduced into the ABL1 region of a stably expressed p210 BCR-ABL fusion in Ba/F3 cells using N-ethyl-N-nitrosourea mutagenesis. Resulting clones were grown in a range of tyrosine kinase inhibitor concentrations to identify resistance mutations. The T315I mutation was associated with resistance in 400 nM imatinib + 10 nM dasatinib (10 clones, ~91%), 2 μM imatinib + 50 nM dasatinib (8 clones, 100%), and 4 μM imatinib + 100 nM dasatinib (8 clones, 100%) combination treatments.
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/6234
Gene URL
https://civic.genome.wustl.edu/links/genes/4
Variant URL
https://civic.genome.wustl.edu/links/variants/2
Rating
3
Evidence Type
Predictive
Disease
Chronic Myeloid Leukemia
Evidence Direction
Supports
Drug
Dasatinib,Imatinib Mesylate
Evidence Level
D
Clinical Significance
Resistance
Pubmed
16772610
Drugs
Drug NameSensitivitySupported
DasatinibResitance or Non-Reponsetrue
Imatinib MesylateResitance or Non-Reponsetrue