The Manalis lab’s platform detects and extracts rare circulating tumor cells from live mouse models using a combination of laser excitation and a microfluidic chip (pictured), and can be used to answer important questions in cancer biology and care.
MIT Koch Institute
April 20, 2024
Leukemias and their bone marrow microenvironments undergo dynamic changes over the course of disease. However, little is known about the circulation kinetics of leukemia cells, or the impact of specific factors on the clearance of circulating leukemia cells (CLCs) from the blood by normal filtration mechanisms.
Professors Scott Manalis and Michael Hemann published a new study of leukemia cell behaviors in Communications Biology that improves our basic understanding of CLC dynamics over the course of disease progression and therapeutic response. Understanding these circulation kinetics and clearance rates can inform our biological understandings of metastasis, as well as the design of tools that target these circulating cells for cancer diagnosis, treatment and monitoring.
Manalis and Hemann used a blood exchange method, which operates similarly to dialysis, to study mouse models of leukemia. This method employs a microdevice-driven cell sorting platform previously developed by the Manalis Lab with other Koch Institute collaborators.
The cell-sorting chip stemmed from a conversation in the Koch Café lunch line between Manalis and Tyler Jacks, David H. Koch (1962) Professor of Biology. They had seen a presentation from a graduate student working in the laboratory of Matthew Vander Heiden about a dialysis-like system to track metabolites in the bloodstream of mice. Jacks and Manalis wondered if a similar approach could be used to study rare circulating tumor cells in real-time, even in mice—something made exceedingly difficult by the low blood volume of mice, rarity of circulating tumor cells, and limitations of available technology. Drawing from multiple areas of expertise around the Koch Institute, Jacks and Manalis developed a real-time cell sorter, that enabled researchers, for the first time, to longitudinally collect circulating tumor cells from the same mouse.
Using the platform in their new study, Manalis and Hemann found that CLCs circulate in the blood for 1–2 orders of magnitude longer than circulating tumor cells from solid tumors. They also observed in an acute lymphocytic leukemia model that leukemia presence in bone marrow can limit the clearance of CLCs, and in a model of relapsed acute myeloid leukemia that CLCs can clear faster than in their untreated counterparts. Further, this blood exchange approach can also directly quantify the impact of microenvironmental factors on CLC clearance properties. For example, data from two leukemia models suggest that E-selectin, a vascular adhesion molecule, alters CLC clearance.
The team’s research highlights that clearance rates of CLCs can vary in response to tumor and treatment status and provides a strategy for identifying basic processes and factors that govern the kinetics of circulating cells. Findings from this work could help improve the design of blood biopsy technologies, personalized treatment regimens, and other detection and treatment applications.