Clonal proliferation is triggered by the acquisition of somatic mutations in specific myeloid genes, operationally classified in driver mutations, e.g., JAK2V617F and JAK2 exon 12 mutations, MPLW515 mutations, and CALR indels, covering virtually all PV cases (~99%) and the vast majority of ET and PMF cases (85–90%), and less common non-driver mutations, including TET2, ASXL1, IDH1/2, EZH2, SRSF2, LNK, CBL, TP53, etc., occurring in fewer than 30% of patients during chronic phase but typically increasing with disease progression (accelerated/blast phase) [2]. The gene discussed is CALR; the disease is essential thrombocythemia.