Novel Drivers and Modifiers of MPL-dependent Oncogenic Transformation Identified by Deep Mutational Scanning

The single transmembrane domain of the human thrombopoietin receptor (TpoR/MPL), encoded by exon 10 of the MPL gene, is a hotspot for somatic mutations associated with myeloproliferative neoplasms. The project was designed to identify all single-amino-acid substitutions in the human TpoR transmembrane and partial juxtamembrane regions (488-516) that could independently confer factor-free growth or enhance the factor-free growth phenotype of TpoR S505N as second-site mutations.