Annotation Detail
Information
- Associated Genes
- ABL1
- Associated Variants
-
ABL1 p.Phe378Cys (p.F378C)
(
ENST00000318560.6,
ENST00000372348.9 )
ABL1 p.Phe378Cys (p.F378C) ( ENST00000318560.6, ENST00000372348.9 ) - 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 of >150nM. In patients with F359C and/or F359V mutations prior to nilotinib treatment, complete hematological responses were achieved in 3 of 10 patients, a major cytogenetic response in 1 of 11 patients, a complete cytogenetic response in 0 of 11 patients, and major molecular response in 0 of 10 patients. After a median follow-up of 15.5 months, 9 of 11 patients with this mutation progressed or died. The F359C mutation was present in 1 patient at baseline and newly emerged in 1 patient at progression. The F359V mutation was present in 4 patients at baseline and newly emerged in 1 patient at progression.
- Variant Origin
- somatic
- Variant Origin
- Somatic
- Evidence URL
- https://civic.genome.wustl.edu/links/evidence_items/6233
- Gene URL
- https://civic.genome.wustl.edu/links/genes/4
- Variant URL
- https://civic.genome.wustl.edu/links/variants/1184
- Rating
- 3
- Evidence Type
- Predictive
- Disease
- Chronic Myeloid Leukemia
- Evidence Direction
- Supports
- Drug
- Imatinib Mesylate,Nilotinib
- 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 |