Annotation Detail
Information
- Associated Genes
- ABL1
- Associated Variants
- ABL1 SNX2-ABL1 Fusion
- Associated Disease
- Pediatric B-cell Acute Lymphoblastic Leukemia
- Source Database
- CIViC Evidence
- Description
- SNX2-ABL1 protein (SNX2 exon 3 to ABL1 exon 4) was transfected in murine Ba/F3 cells and proliferation rates in the presence of IL-3, and tyrosine kinase inhibitors, imatinib and dasatinib was compared to BCR-ABL1 p190 and p210 transfected Ba/F3 cells. Cell proliferation assays showed that SNX2-ABL1 transfected cells had over 20% and 50% of cell survival after 24-hr incubation with imatinib (2µM) and dasatinib (10nM). SNX2-ABL1 transfected cells continued to proliferate again 48 hr after treatment with dasatinib (10nM). This data was further supported by apoptosis (annexin V-propidium iodide) studies. In addition, newer tyrosine kinase inhibitors including nilotinib (500nM), bafetinib (500nM), rebastinib (500nM), and ponatinib (100nM), were examined and SNX2-ABL1 cells showed a better response, but still some resistance to these compounds. Further examination of downstream phosphorylation of SNX2-ABL1 cells showed only partial inhibition with imatinib and dasatinib.
- Variant Origin
- somatic
- Variant Origin
- Somatic
- Evidence URL
- https://civic.genome.wustl.edu/links/evidence_items/7655
- Gene URL
- https://civic.genome.wustl.edu/links/genes/4
- Variant URL
- https://civic.genome.wustl.edu/links/variants/2678
- Rating
- 3
- Evidence Type
- Predictive
- Disease
- Pediatric B-cell Acute Lymphoblastic Leukemia
- Evidence Direction
- Supports
- Drug
- Dasatinib,Imatinib
- Evidence Level
- D
- Clinical Significance
- Resistance
- Pubmed
- 24367893