Authors: Jia He, Khalid A Hajj, Christopher M Knapp and Kathryn A Whitehead
Summary: Mantle cell lymphoma is an aggressive subtype of non-Hodgkin’s lymphoma that claims the lives of tens of thousands of people every year. Although combination chemotherapy treatments such as CHOP have yielded promising outcomes in the clinic, the development of chemoresistance in patients has limited their long-term success. The lack of in vitro chemoresistance models has limited our ability to understand the mechanisms by which cells develop resistance, and thus our ability to develop novel therapeutics to overcome this issue. Here, we describe the development of a clinically relevant chemoresistant mantle cell lymphoma model using the JeKo-1 cell line. This was achieved through a stepwise treatment selection strategy using gradually increasing concentrations of CHOP. We show that resistant JeKo-1 cells display strong recovery and fast proliferation after treatment with an IC50 dose of CHOP. We also found that resistant JeKo-1 cells overexpress three oncogenes implicated in the development of mantle cell lymphoma—Cyclin D1, Mcl-1, and Bcl-2—compared to normal JeKo-1 cells. We anticipate that in vitro models such as this one will enable the discovery of new therapeutic strategies for overcoming chemoresistance and improve clinical outcomes in mantle cell lymphoma patients.
Keywords: Chemoresistance, lymphoma, in vitro models, CHOP
Source: Experimental Biology and Medicine 2019; 244: 865–872