A New Model for Lymphoma Drug Discovery

WASHINGTON, August 10, 2019 (Newswire.com) - ​An article published in Experimental Biology and Medicine (Volume 244, Issue 11, August, 2019) (https://journals.sagepub.com/doi/pdf/10.1177/1535370219857594) describes a new drug discovery model for mantle cell lymphoma, a deadly subtype of non-Hodgkin’s lymphoma. The study, led by Dr. Kathryn Whitehead in the Departments of Biomedical Engineering and Chemical Engineering at Carnegie Mellon University in Pittsburgh, Pennsylvania (USA), reports the development of a drug-resistant cell line that recapitulates the chemoresistance typically observed in patients. 

Mantle cell lymphoma is an aggressive subtype of non-Hodgkin’s lymphoma that claims the lives of tens of thousands of people every year. Mantle cell lymphoma is considered incurable, even though new treatments have yielded promising results. The combination chemotherapy regimen CHOP has a high response rate in patients. However, the cancer becomes resistant to treatment over time, and the duration of the response is often less than three years. The development of effective treatments for patients with advanced disease is hampered by the lack of conventional cell culture and preclinical models of mantle cell lymphoma that recapitulate the chemoresistance seen in patients. The lack of chemoresistant models has also limited our understanding of the mechanisms used by cells to acquire resistance. 

In the current study, Dr. Whitehead and colleagues describe the generation of a chemoresistant mantle cell lymphoma cell line that mimics the low level resistance observed in patients. JeKO-1 cells treated with increasing concentrations of the chemotherapy cocktail CHOP developed tolerance to CHOP treatment and exhibited rapid proliferation when exposed to therapeutic levels of CHOP. These cells also exhibited increased expression of three oncogenes implicated in the development of mantle cell lymphoma--Cyclin D1, Mcl-1 and Bcl-1. Dr. Whitehead said “a significant challenge in cancer therapy today is a lack of models that are representative of true human disease. We are pleased to have developed a mantle cell lymphoma cell culture model that recapitulates typical levels of chemoresistance in patients.”

Dr. Steven R. Goodman, Editor-in-Chief of Experimental Biology & Medicine, said “Whitehead and colleagues have provided a clinically relevant in vitro model of mantle cell lymphoma. This model should be extremely valuable in identifying therapeutics that can overcome the issue of drug resistance.”

​Experimental Biology and Medicine is a global journal dedicated to the publication of multidisciplinary and interdisciplinary research in the biomedical sciences. The journal was first established in 1903. Experimental Biology and Medicine is the journal of the Society of Experimental Biology and Medicine. To learn about the benefits of society membership, visit www.sebm.org. If interested in publishing in the journal, please visit http://ebm.sagepub.com.

Source: Experimental Biology and Medicine