M. Talpaz

Lysosomal Degradation Pathways Target Mutant Calreticulin and the Thrombopoietin Receptor in Myeloproliferative Neoplasms

This study shows that mutant calreticulin induces lysosomal degradation of the thrombopoietin receptor in MPNs, and drug-induced lysosomal activation reduces mutant protein levels and pathogenic effects.

Mpl is activated by dimers of MPN-linked calreticulin mutants stabilized by disulfide bonds and ionic interactions

This study identifies how mutated calreticulin (CRTDel52) forms dimers stabilized by disulfide bonds and ionic interactions, leading to Mpl activation and cytokine-independent cell proliferation in MPNs.