Annotation Detail
Information
- Associated Genes
- PRPS1
- Associated Variants
-
PRPS1 S103I
PRPS1 S103I - Associated Disease
- childhood B-cell acute lymphoblastic leukemia
- Source Database
- CIViC Evidence
- Description
- Lentiviral-mediated overexpression of PRPS1 S103I in Reh cells resulted in significant resistance against mercaptopurine (6-MP) and thioguanine (6-TG) as indicated by IC50 increases and reduced apoptosis compared to multiple controls (empty vector and overexpression of wildtype or known reduced-function PRPS1 mutants). After 6-MP exposure, mass spectrometry revealed S103I cells possessed reduced concentrations of intracellular 6-MP metabolites (TIMP, TGMP, etc.) versus controls. S103I cells produce increased intracellular concentrations of hypoxanthine and IMP. The enhanced production of hypoxanthine likely leads to reduced conversion of thiopurines to their active form due to competitive inhibition.
- Variant Origin
- somatic
- Variant Origin
- Somatic
- Evidence URL
- https://civic.genome.wustl.edu/links/evidence_items/7905
- Gene URL
- https://civic.genome.wustl.edu/links/genes/4566
- Variant URL
- https://civic.genome.wustl.edu/links/variants/2925
- Rating
- 4
- Evidence Type
- Predictive
- Disease
- Childhood B-cell Acute Lymphoblastic Leukemia
- Evidence Direction
- Supports
- Drug
- Mercaptopurine,Thioguanine
- Evidence Level
- D
- Clinical Significance
- Resistance
- Pubmed
- 25962120
Drugs
| Drug Name | Sensitivity | Supported |
|---|---|---|
| Mercaptopurine | Resitance or Non-Reponse | true |
| Thioguanine | Resitance or Non-Reponse | true |