The germline sequence variant rs2736100_C in TERT associates with myeloproliferative neoplasms

Myeloproliferative neoplasms (MPN) constitute a group of clonal hematological disorders characterized by an expansion and accumulation of one or more mature cell types of the myeloid lineages. There are four main groups of MPNs that can be classified by the presence or absence of the Philadelphia (Ph) chromosome. 1 Chronic myeloid leukemia is accompanied by the Ph chromosome, whereas polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) are not. 1 In all three Ph-negative MPN subtypes (hereafter called MPN), a recurrent somatic mutation is frequently found in the pseudokinase region of Janus kinase 2 (JAK2 V617F ). 2 The mutation is observed in about 80–95% of PV cases, 50% of ET cases and 60% of PMF cases. 2 Owing to the activating nature of the mutation, it leads to constant stimulation of myeloid proliferation. 2 Family studies have shown that germline variants may predispose to the disease as the risk of MPN among first-degree relatives of MPN patients in Sweden is five to sevenfold greater than that in the general population. 2 Furthermore, common germline single-nucleotide polymorphisms (SNPs) at the JAK2 locus have been associated with MPN. 3 , 4 , 5