Three classes of somatic activating driver mutations localized within specific exons of Janus Kinase 2 (JAK2), thrombopoietin receptor (MPL/TPOR) and calreticulin (CALR) genes are key players in the majority of MPNs2 leading to an improper activation of JAK2 signalling.3 The single HSC that harbours the oncogenic mutation—MPN stem cell—has to acquire a selective advantage over its normal counterpart to ensure the clonal expansion needed for the development of an MPN phenotype. This evidence concerns the gene MPL and myeloproliferative disorder.