Decreased sensitivity of cyclin-dependent kinase 4/6 inhibitors, palbociclib and abemaciclib to canine lymphoma cells with high p16 protein expression and low retinoblastoma protein phosphorylation

Canine lymphoma/leukemia cell lines with p16 protein expressions: high (17-71 and GL-1) and low (CLBL-1, CLC, Nody-1, and UL-1) were treated in vitro with cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, palbociclib or abemaciclib. Cell proliferation decreased as a result, with higher IC50 levels observed in the high p16 (17-71 and GL-1) and one low p16 (UL-1) cell lines compared with the low p16 cells (CLBL-1, CLC, and Nody-1). As expected, palbociclib and abemaciclib treatment reduced pRb phosphorylation in a dose-dependent manner, especially in cells with low p16. These results suggest that CDK4/6 inhibitors have potential as new chemotherapeutic agents for canine lymphoma and high p16 protein expression may be used as a biomarker for resistance to CDK4/6 inhibitor therapy.

Automated summary

Canine lymphoma/leukemia cell lines with high (17-71 and GL-1) and low (CLBL-1, CLC, Nody-1, and UL-1) p16 protein expressions were treated in vitro with CDK4/6 inhibitors, palbociclib or abemaciclib. The cell proliferation decreased with higher IC50 levels in high p16 and one low p16 cell lines compared to low p16 cells. The CDK4/6 inhibitors reduced pRb phosphorylation in a dose-dependent manner, especially in cells with low p16, suggesting their potential as new chemotherapeutic agents for canine lymphoma, while high p16 expression may indicate resistance to CDK4/6 inhibitor therapy.