In vitro sensitivity of T-cell lymphoblastic leukemia to UCN-01 (7-hydroxystaurosporine) is dependent on p16 protein status: a Pediatric Oncology Group study
| Autor: | Omura-Minamisawa M, Mb, Diccianni, Batova A, Rc, Chang, Lj, Bridgeman, Yu J, de Wit E, Fh, Kung, Jd, Pullen, alice yu |
|---|---|
| Předmět: |
Gene Expression Regulation
Leukemic Reverse Transcriptase Polymerase Chain Reaction Tumor Suppressor Proteins Antineoplastic Agents Cell Cycle Proteins Staurosporine Retinoblastoma Protein Alkaloids Tumor Cells Cultured Humans Leukemia-Lymphoma Adult T-Cell Gene Silencing Phosphorylation Carrier Proteins Cyclin-Dependent Kinase Inhibitor p16 Gene Deletion Cyclin-Dependent Kinase Inhibitor p15 |
| Zdroj: | Europe PubMed Central |
| Popis: | p16 regulates the cell cycle pathway by inhibiting the cyclin Ds-cyclin-dependent kinase (CDK) 4/6-mediated phosphorylation of retinoblastoma protein (pRb). Previously, we reported that most primary T-cell acute lymphoblastic leukemia (T-ALL) harbored p16 inactivation and hyperphosphorylated pRb without cyclin Ds or CDK4/6 alterations. Therefore, inhibiting CDK4/6 may be an ideal therapeutic approach for p16 (-) T-ALL. UCN-01 (7-hydroxystaurosporine) is a potent antitumor agent that exerts its effects through the inhibition of CDKs. We now report that p16 protein expression status of T-ALL cells influences their sensitivity to UCN-01. In 36 primary T-ALL cells, the IC50s of UCN-01 in the 27 p16 (-) cells (43+/-52 nM) was significantly lower than that in the 9 p16 (+) cells (258+/-260 nM). Our results suggest that agents like UCN-01 may be useful as a p16-selective therapy for T-ALL. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|