Abstract
High-throughput DNA sequence analysis was used to screen for TET2 mutations in peripheral blood derived DNA from 97 patients with BCR-ABL-negative myeloproliferative neoplasms (MPNs). Overall six mutations in the coding region of the gene were identified in 7 patients with an overall mutational frequency of 7.2%. In polycythemia vera patients (n = 25) 2 mutations were identified (8%), and in those with essential thrombocythemia (n = 55) 2 mutations (3.6%); in those with unclassifiable MPN (n = 8) 3 mutations (37.5%). No primary myelofibrosis patients (n = 6) harboured TET2 mutations. Three unreported mutations were identified (p.P177fs, p.C1298del, and p.P411del), the first two in patients with unclassifiable MPN, the last in a patient with essential thrombocythemia. On multivariate analysis the diagnosis of an unclassifiable MPN was significantly related to the presence of TET2 mutations (P = 0.02; OR: 2.81; 95% CI 1.11–7.06). We conclude that TET2 mutations occur in both JAK2 V617F-positive and -negative MPNs and are more frequent in MPN-U patients. This could represent the biological link between the different classes of myeloid malignancies.
Highlights
Philadelphia-negative myeloproliferative neoplasms (MPNs) are a spectrum of clonal disorders of the hematopoietic system characterized by overproduction of mature blood elements, a trend to thrombotic and/or hemorrhagic complications with variable rates of transformation to secondary myelofibrosis and acute leukemia [1]
In addition to the expected differences in full blood count, frequency of splenomegaly, JAK2 V617F allele burden, bone marrow cellularity, depending on specific MPN subtype, we found that the polycythemia vera (PV) patients were significantly older than the other patients (P = 0.04), and essential thrombocytemia (ET) patients were more often females (P = 0.04)
No significant difference was observed between patients with/without TET2 mutations as far as the JAK2 V617F frequency is concerned (Table 3)
Summary
Philadelphia-negative myeloproliferative neoplasms (MPNs) are a spectrum of clonal disorders of the hematopoietic system characterized by overproduction of mature blood elements, a trend to thrombotic and/or hemorrhagic complications with variable rates of transformation to secondary myelofibrosis and acute leukemia [1]. The presence of JAK2 or MPL mutations represents major diagnostic criteria in the WHO classification of classic BCR-ABL-negative MPNs. a variable percentage of patients lack both molecular markers. At the best of our knowledge, no significant correlation was observed between the TET2 mutation status and both the clinical-laboratory phenotype and the risk of secondary clonal evolution in MPNs [6]. Aims of our study were (1) to investigate the presence of TET2 mutations in MPN patients with or without the JAK2 V617F mutation and (2) to establish a possible relationship between clinical and laboratory findings in the context of BioMed Research International polycythemia vera (PV), essential thrombocytemia (ET), primary myelophibrosis (PMF) and myeloproliferative neoplasms unclassifiable (MPNs-U)
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