Annotation Detail
Information
- Associated Genes
- ABL1
- Associated Variants
- ABL1 p.Glu274Lys (p.E274K) ABL1 p.Glu274Lys (p.E274K)
- Associated Disease
- chronic myeloid leukemia
- Source Database
- CIViC Evidence
- Description
- In this open-label, phase II registration trial, patients that were imatinib resistant or intolerant underwent nilotinib monotherapy. Within 12 months of nilotinib therapy, there was no significant difference in response to nilotinib treatment between patients with mutations in the Abl1 kinase domain versus without. However, the authors identify Y253H, E255K/V, and F359C/V variants as resistant as they had an IC50 greater than 150 nM. In patients with E255K and/or E255V mutations prior to nilotinib treatment, complete hematological responses were achieved in 5 of 7 patients, major cytogenetic responses in 3 of 7 patients, complete cytogenetic responses in 0 of 7 patients, and a major molecular response in 1 of 7 patients. After a median follow-up of 15.5 months, 6 of 7 patients with this mutation progressed or died. The E255K mutation was present in 6 patients at baseline and newly emerged in 4 patients at progression. The E255V mutation was present in 0 patients at baseline and newly emerged in 3 patients at progression.
- Variant Origin
- somatic
- Variant Origin
- Somatic
- Evidence URL
- https://civic.genome.wustl.edu/links/evidence_items/6232
- Gene URL
- https://civic.genome.wustl.edu/links/genes/4
- Variant URL
- https://civic.genome.wustl.edu/links/variants/3
- Rating
- 3
- Evidence Type
- Predictive
- Disease
- Chronic Myeloid Leukemia
- Evidence Direction
- Supports
- Drug
- Nilotinib,Imatinib Mesylate
- Evidence Level
- C
- Clinical Significance
- Resistance
- Pubmed
- 19652056
Drugs
| Drug Name | Sensitivity | Supported |
|---|---|---|
| Imatinib Mesylate | Resitance or Non-Reponse | true |
| Nilotinib | Resitance or Non-Reponse | true |