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 this study, enzymatic profiling, crystal structures, and proliferation assays using Ba/F3 with the BCR-ABL1 variant showed higher sensitivity to axitinib in fusions with the T315I variant of ABL1 compared to wildtype ABL1 (IC50 of 21nM vs. 217 nM in resazurin assay; IC50 of 98 nM vs. 823 nM in tritiated thymidine assay). Bone marrow mononuclear cells (BM MNCs) were isolated from a chronic myeloid leukemia patients with the BCR-ABL1 T315I variant who was pretreated with imatinib, dasatinib, and chemotherapy. This patient's cells were sensitive to Ponatinib and Axitinib and insensitive to Nilotinib, Imatinib, and Dasatinib according to drug sensitivity scoring in proliferation assays. The patient was given axitinib monotherapy resulting in a significant decrease in T315I transcript levels in bone marrow (P<0.05). The authors note this as an example of a drug specifically targeting the secondary mutant resistant form of a protein.
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/4369
Gene URL
https://civic.genome.wustl.edu/links/genes/4
Variant URL
https://civic.genome.wustl.edu/links/variants/2
Rating
4
Evidence Type
Predictive
Disease
Chronic Myeloid Leukemia
Evidence Direction
Supports
Drug
Axitinib
Evidence Level
C
Clinical Significance
Sensitivity/Response
Pubmed
25686603
Drugs
Drug NameSensitivitySupported
AxitinibSensitivitytrue