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Myeloproliferative neoplasms other than CML are grouped as policytemia vera (PV), essential trombocythemia (ET) and primary myelofibrosis (PMF). By the identification of JAK2617f mutation in 2005; the explanation of the clonal proliferation in 90-95% of PV, 50% of ET and 50% of PMF have been possible. Thereafter JAK exon-12 mutations for PV and MPL mutations for ET and PMF have been  defined. However the clonal proliferation in approximately half of the ET and PMF cases  have been undetermined. One of the many mutations which could have a role in the pathogenesis is TET2 mutations. TET2 mutations were found  positive in 15% of PV, 4-11% of ET and 19% of PMF patients. Some studies also showed that TET2 mutations have prognostic value.

Our aims are the determination and clinical relevance of TET2 mutations in patients with ET and PMF which are following in our clinic. 

35 ET ve 10 PMF patiens are included according to WHO criteria. Patients’ demographic informations, clinical and laboratory findings were registered. DNAs were isolated from venous blood samplings and all exons of the TET2 gene were analyzed by Sanger based sequencing method. Informed consent was obtained from all patients. In addition to descriptive statistics, datas were evaluated for the comprasion of two groups with t test, chi-square test and Odds Ratio.

TET2 mutations were found in 47,5% (16/35) of ET patients and 70% (7/10) of PMF patients. Six mutations were defined: I1762V, M1907T, L1721W, H1778A, C1298Y and Q1828X. Of these, L1721W and I1762V have possibility of being a genetic polymorphism. The frequency of TET2 mutation was not statistically different between sex and age. We demonstrated a correlation between initial spleen size and TET2 mutations for patients with ET (p=0.011). Increased bone marrow fibrosis is also found in bone marrow biopsy examination in TET2 mutation-positive ET patients (p=0,011). Furthermore, complications including arterial thrombosis and bleeding are found more frequent in TET2 mutations positive ET and PMF patients (for ET relatively OR:2,59, for PMF relatively OR:1,7, OR:1,6). Togetherness of JAK2V617F and TET2 mutations associates bigger spleen size (p=0,001) and increased risk of arterial thrombosis and bleeding in patients with ET and PMF (for ET, relatively OR:3,85, OR:2,8; for PMF, relatively OR:3,67, OR:3,67). 

We herein found higher rates of TET2 mutations in patients with ET and PMF. Positivity of TET2 mutations are correlated with especially spleen size and the rate of fibrosis for patients with ET; and these mutations increase the risk of arterial thrombosis and bleeding. For patients with PMF, positivity of TET2 mutations increase spleen size and the risk of arterial thrombosis and bleeding. Togetherness of JAK2V617F and TET2 is associated with increased risk of complications. We conclude that to know the TET2 mutations in ET and PMF can give information about disease progression and complications thus may identify a high-risk subgroup of MPN patients.