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
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. The patient's cells were sensitive to Ponatinib and Axitinib and insensitive to Nilotinib, Imatinib, and Dasatinib compared to BM MNCs from healthy controls using drug sensitivity scoring of proliferation assays. Additionally, in a rezasurin proliferation assay, Ba/F3 cells carrying the BCR-ABL1 variant were resistant to imatinib in fusions with the T315I variant of ABL1 compared to wildtype ABL1 (IC50 of >4,000 nM vs. 257 nM).
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/7780
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
Nilotinib,Imatinib,Dasatinib
Evidence Level
D
Clinical Significance
Resistance
Pubmed
25686603
Drugs
Drug NameSensitivitySupported
DasatinibResitance or Non-Reponsetrue
ImatinibResitance or Non-Reponsetrue
NilotinibResitance or Non-Reponsetrue