Ribociclib, A Cdk4/Cdk6 Kinase Inhibitor, Enhances Glucocorticoid Sensitivity In B-Acute Lymphoblastic Leukemia (B-All).

Ribociclib, A Cdk4/Cdk6 Kinase Inhibitor, Enhances Glucocorticoid Sensitivity In B-Acute Lymphoblastic Leukemia (B-All). Biochem Pharmacol. 2018 Feb 03;: Authors: Bortolozzi R, Mattiuzzo E, Trentin L, Accordi B, Basso G, Viola G Abstract Dysregulation of the cyclin D1-CDK4/CDK6 complex is frequently observed in almost all human cancer and contributes to aberrant cell proliferation and consequent tumorigenesis. Although many reports described the importance of CDK4/CDK6 in different set of human tumors, only few studies have been performed on leukemia. By gene expression analysis performed in a cohort of childhood patients affected by B-acute lymphoblastic leukemia (B-ALL) we found that both CDK4 and CDK6 are highly expressed. Moreover, Reverse Phase Protein Array (RPPA) analysis showed that cyclin D1 levels are higher in patients undergoing relapse. Starting from these considerations, we evaluated the effect of dual inhibition of CDK4/CDK6 in B-ALL and if this inhibition could enhance cytotoxic killing of leukemia cells after combination treatment with dexamethasone. We treated B-ALL cell lines with ribociclib, a highly specific CDK4/6 inhibitor. As expected, treatment with ribociclib induced growth inhibition of B-ALL cell lines, accompanied by strong cell cycle arrest in G1 phase, along with a dose-dependent decrease in phosphorylated retinoblastoma protein. Ribociclib exposure strongly synergize with dexamethasone in SEM and RCH-A...
Source: Biochemical Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Biochem Pharmacol Source Type: research