MAPK-Erk1/2 Pathway Activation and Survival Of Chronic Lymphocytic Leukemia (CLL) Cells Is Induced By In Vitro Modeling Of The Tumor Microenvironment and Can Be Effectively Inhibited Using The MEK1 Inhibitor MEK162
Best OG, Crassini K, Stevenson WS, et al.
Key Points:
Demonstration of anti-tumor activity of MEK inhibitors in preclinical models of CLL hampered by loss of MAPK-Erk1/2 signaling in CLL cells during ex vivo processing and culture
Adding purified stroma-derived factor (SDF-1a/CXCL12) or media conditioned by the HS5 stromal cell line allowed re-activation of the pathway
Increased CLL cell sensitivity to MEK inhibitors also demonstrated in pretreated ex vivo system
Implications:
- inhibition of MEK1/2 may represent novel treatment strategy for CLL
View the original abstract on the ASH website.
