Survey of ex vivo drug combination effects in chronic lymphocytic leukemia reveals synergistic drug effects and genetic dependencies

CD38 gene polymorphisms and genetic susceptibility to chronic lymphocytic leukemia

Introduction: CLL is one of the most common leukemias, which is categorized by the accumulation of mature CD5+ B-lymphocytes in the peripheral blood, bone marrow, and secondary lymphoid organs. In this study, the status of rs6449182 polymorphism of the CD38 gene and its association with clinical and laboratory parameters of CLL patients was evaluated. Methods: Genomic DNA extraction was perfor...

Ex vivo study of the effect of an anti-proliferative drug in Chronic Lymphocytic Leukemia cells mimicking proliferative niches microenvironment

Drug-Drug Interactions: Influence of verapamil on the pharmacokinetics of sitagliptin in rats and Ex vivo models

P-glycoprotein (P-gp) and cytochrome P450 3A4 (CYP3A4) play a significant role in the disposition and elimination of drugs. The objective of this study was to investigate the mechanism underlying the interaction between sitagliptin (substrate of P-gp and CYP3A4) and verapamil (known modulator of P-gp and CYP3A4) using in vivo, ex vivo and in situ models. Rats were treated with sitagliptin (10 m...

Personalized Drug Analysis in B Cell Chronic Lymphocytic Leukemia Patients

BACKGROUND B cell chronic lymphocytic leukemia (B-CLL) is the most common adult leukemia in the Western world. Although therapeutic advances have notably improved the outcome for many patients, B-CLL remains an incurable disease. The purpose of this study was to search for therapeutic drugs based on altered pathways in individual patients. MATERIAL AND METHODS Genes from microarray data were ma...

Idelalisib and bendamustine combination is synergistic and increases DNA damage response in chronic lymphocytic leukemia cells

Idelalisib is a targeted agent that potently inhibits PI3Kδ which is exclusively expressed in hematological cells. Bendamustine is a well-tolerated cytotoxic alkylating agent which has been extensively used for treatment of chronic lymphocytic leukemia (CLL). Both these agents are FDA-approved for CLL. To increase the potency of idelalisib and bendamustine, we tested their combination in primar...