Annotation Detail

Information
Associated Genes
ALK
Associated Variants
ALK NPM-ALK
Associated Disease
anaplastic large cell lymphoma
Source Database
CIViC Evidence
Description
NPM-ALK in anaplastic large cell lymphoma (ALCL) was the first ALK-fusion to be discovered and characterized. In this study, targeted activity against NPM-ALK by the ALK and MET inhibitor crizotinib was assessed in cell lines and tumor xenograft models. Treatment of NPM-ALK positive ALCL cell lines Karpas299 and SU-DHL-1 potently inhibited growth, and this was seen to occur at concentrations which also inhibited NPM-ALK phosphorylation in these cells. Administration of 100mg/kg/d crizotinib resulted in complete regression of all tumors, indicating that NPM-ALK could be an effective target for crizotinib in ALCL.
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/1239
Gene URL
https://civic.genome.wustl.edu/links/genes/1
Variant URL
https://civic.genome.wustl.edu/links/variants/513
Rating
5
Evidence Type
Predictive
Disease
Anaplastic Large Cell Lymphoma
Evidence Direction
Supports
Drug
Crizotinib
Evidence Level
D
Clinical Significance
Sensitivity/Response
Pubmed
18089725
Drugs
Drug NameSensitivitySupported
CrizotinibSensitivitytrue