Tracking leukemic T-cell transcriptional dynamics in vivo with a blood-based reporter assay

Abstract

Transcriptional dynamics of cancer cells govern cell fate decisions and are therapeutically actionable drug targets. In this study, we engineered a circulating cancer cell line that secretes a luciferase reporter to capture constitutive and circadian clock-driven transcription dynamics over the course of a day. Engineered human leukemic T cells (Jurkat) were observed to rhythmically secrete luciferase in a continuous flow cell culture system. When transplanted in vivo, engineered leukemic cells caused circadian plasma luciferase activity and had expected pathological signs of leukemic disease. This technique is rapid and noninvasive, requiring only a few microliters of media or blood, and can aid in investigating relationships between in vivo cancer cell signaling and behavior, such as diet or sleep.

Keywords: circadian clocks; leukemic T cells; secreted luciferase; transcriptional reporter.