DEGRADATION OF MUTANT CALRETICULIN AND MPL IN MPN

In this study, we measured the relative levels of MPL protein in platelets purified from patients with MPN and healthy donors and found a significant reduction in MPL levels in platelets of patients with MPN. We used model cell lines co-expressing human MPL and mutant CRT proteins to explore the pathways involved in the regulation of surface MPL and mutant CRT levels. Our findings indicate that the induced degradation of mutant CRT and MPL can be used therapeutically to compromise the cell-transforming effects of mutant CRT.