Telomerase activity, apoptosis and cell cycle progression in ataxia telangiectasia lymphocytes expressing TCL1

Individuals affected by ataxia telangiectasia (AT) have a marked susceptibility to cancer. Ataxia telangiectasia cells, in addition to defects in cell cycle checkpoints, show dysfunction of apoptosis and of telomeres, which are both thought to have a role in the progression of malignancy. In 1-5% of patients with AT, clonal expansion of T lymphocytes carrying t(14;14) chromosomal translocation, deregulating TCL1 gene(s), has been described. While it is known that these cells can progress with time to a frank leukaemia, the molecular pathway leading to tumorigenesis has not yet been fully investigated. In this study, we compared AT clonal cells, representing 88% of the entire T lymphocytes (AT94-1) and expressing TCL1 oncogene (ATM- TCL1 +), cell cycle progression to T lymphocytes of AT patients without TCL1 expression (ATM- TCL1-) by analysing their spontaneous apoptosis rate, spontaneous telomerase activity and telomere instability. We show that in ATM- TCL1+ lymphocytes, apoptosis rate and cell cycle progression are restored back to a rate comparable with that observed in normal lymphocytes while telomere dysfunction is maintained. © 2003 Cancer Research UK

Clinical Pharmacology in the Adolescent Oncology Patient

Numerous studies have documented that adolescents and young adults (AYAs) experience a significant cancer burden as well as significant cancer mortality compared with other age groups. The reasons for the disparate outcomes of AYAs and other age groups are not completely understood and are likely to be multifactorial, including a range of sociodemographic issues unique to these individuals as well as differences between adolescents, younger pediatric patients, and adults in the pharmacology of anticancer agents. Because adolescence is a period of transition from childhood to early adulthood, numerous physical, physiologic, cognitive, and behavioral changes occur during this time. In this review, we provide an overview of the unique developmental physiology of the adolescent and explain how these factors and the behavioral characteristics of adolescents may affect the pharmacology of anticancer agents in this patient population. Finally, we describe examples of studies that have assessed the relation between drug disposition and age, focusing on the AYA age group