In vitro sensitivity of T-cell lymphoblastic leukemia to UCN-01 (7-hydroxystaurosporine) is dependent on p16 protein status : A pediatric oncology group study

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 wit...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2000-12, Vol.60 (23), p.6573-6576
Main Authors: OMURA-MINAMISAWA, Motoko, DICCIANNI, Mitchell B, BATOVA, Ayse, CHANG, Ray C, BRIDGEMAN, Louis J, YU, John, DE WIT, Esther, KUNG, Faith H, PULLEN, Jeanette D, YU, Alice L
Format: Article
Language:English
Subjects:
7-hydroxystaurosporine
Alkaloids - toxicity
Antineoplastic agents
Antineoplastic Agents - toxicity
Biological and medical sciences
Carrier Proteins - biosynthesis
Carrier Proteins - genetics
Cell Cycle Proteins
Cyclin-Dependent Kinase Inhibitor p15
Cyclin-Dependent Kinase Inhibitor p16 - biosynthesis
Cyclin-Dependent Kinase Inhibitor p16 - genetics
Cyclin-Dependent Kinase Inhibitor p16 - physiology
Gene Deletion
Gene Expression Regulation, Leukemic
Gene Silencing
General aspects
Humans
Leukemia-Lymphoma, Adult T-Cell - drug therapy
Leukemia-Lymphoma, Adult T-Cell - genetics
Leukemia-Lymphoma, Adult T-Cell - metabolism
Medical sciences
p16 protein
Pharmacology. Drug treatments
Phosphorylation
Retinoblastoma Protein - biosynthesis
Retinoblastoma Protein - genetics
Retinoblastoma Protein - metabolism
Reverse Transcriptase Polymerase Chain Reaction
Staurosporine - analogs & derivatives
Tumor Cells, Cultured
Tumor Suppressor Proteins
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Summary: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.
ISSN:0008-5472
1538-7445