Annotation Detail

Information
Associated Genes
NPM1
Associated Variants
NPM1 EXON 12 MUTATION
NPM1 EXON 12 MUTATION
Associated Disease
acute myeloid leukemia
Source Database
CIViC Evidence
Description
Peripheral blood from NPM1 mutated AMLs was assessed for NPM1 mutation status at multiple time points using RT-qPCR with primers designed to amplify different mutant NPM1 transcripts. The test development cohort consisted of 194 cases and an independent validation cohort consisted of 91 cases. Persistence of NPM1-mutated transcripts in blood was present in 15% of the patients after the second chemotherapy cycle. This persistence was associated with a greater risk of relapse after 3 years of follow-up than was an absence of such transcripts (82% vs. 30%; hazard ratio, 4.80; 95% confidence interval [CI], 2.95 to 7.80; P<0.001) and a lower rate of survival (24% vs. 75%; hazard ratio for death, 4.38; 95% CI, 2.57 to 7.47; P<0.001). The presence of minimal residual disease was the only independent prognostic factor for death in multivariate analysis (hazard ratio, 4.84; 95% CI, 2.57 to 9.15; P<0.001). On sequential monitoring of minimal residual disease, relapse was reliably predicted by a rising level of NPM1-mutated transcripts.
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/1102
Gene URL
https://civic.genome.wustl.edu/links/genes/35
Variant URL
https://civic.genome.wustl.edu/links/variants/86
Rating
4
Evidence Type
Prognostic
Disease
Acute Myeloid Leukemia
Evidence Direction
Supports
Evidence Level
B
Clinical Significance
Poor Outcome
Pubmed
26789727
Drugs