Annotation Detail
Information
- Associated Genes
- PRPS1
- Associated Variants
-
PRPS1 M115T
PRPS1 M115T - Associated Disease
- childhood B-cell acute lymphoblastic leukemia
- Source Database
- CIViC Evidence
- Description
- Lentiviral-mediated overexpression of PRPS1 M115T in Reh cells resulted in similar cytotoxic response (IC50 and apoptosis %) compared to controls (empty vector and wildtype PRPS1 overexpression) after treatment with mercaptopurine (6-MP) or thioguanine (6-TG). After 6-MP exposure, mass spectrometry revealed M115T cells possessed similar concentrations of intracellular 6-MP metabolites (TIMP, TGMP, etc.) versus controls. Intracellular concentrations of hypoxanthine and IMP were similar in M115T cells and controls. After 6-MP exposure, no difference in DNA damage response and apoptosis protein markers were observed between M115T cells and controls.
- Variant Origin
- somatic
- Variant Origin
- Somatic
- Evidence URL
- https://civic.genome.wustl.edu/links/evidence_items/7920
- Gene URL
- https://civic.genome.wustl.edu/links/genes/4566
- Variant URL
- https://civic.genome.wustl.edu/links/variants/2940
- Rating
- 4
- Evidence Type
- Predictive
- Disease
- Childhood B-cell Acute Lymphoblastic Leukemia
- Evidence Direction
- Does Not Support
- Drug
- Mercaptopurine,Thioguanine
- Evidence Level
- D
- Clinical Significance
- Resistance
- Pubmed
- 25962120
Drugs
| Drug Name | Sensitivity | Supported |
|---|---|---|
| Mercaptopurine | Resitance or Non-Reponse | false |
| Thioguanine | Resitance or Non-Reponse | false |