LAUSR

Calreticulin (CALR) mutations are important disease-initiating drivers of myeloproliferative neoplasms (MPNs) and cause hyperproliferation by binding to the thrombopoietin (TPO) receptor and inducing cytokine independent signaling. Jutzi and colleagues report on a CRISPR knockout screen in CALR-mutant cells to identify potential targeted approaches to treating CALR-mutant MPNs. They demonstrated that N-glycosylation of the TPO receptor is necessary for normal surface receptor expression. Chemical inhibition of N-glycosylation impairs growth of CALR-mutant cells but not normal cells, providing a potential for targeted therapy of CALR-mutant MPNs.