Article

TET2 mutations and their clinical correlates in polycythemia vera, essential thrombocythemia and myelofibrosis. Leukemia

Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA.
Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K (Impact Factor: 9.38). 03/2009; 23(5):905-11. DOI: 10.1038/leu.2009.47
Source: PubMed

ABSTRACT High-throughput DNA sequence analysis was used to screen for TET2 mutations in bone marrow-derived DNA from 239 patients with BCR-ABL-negative myeloproliferative neoplasms (MPNs). Thirty-two mutations (19 frameshift, 10 nonsense, 3 missense; mostly involving exons 4 and 12) were identified for an overall mutational frequency of approximately 13%. Specific diagnoses included polycythemia vera (PV; n=89), essential thrombocythemia (ET; n=57), primary myelofibrosis (PMF; n=60), post-PV MF (n=14), post-ET MF (n=7) and blast phase PV/ET/MF (n=12); the corresponding mutational frequencies were approximately 16, 5, 17, 14, 14 and 17% (P=0.50). Mutant TET2 was detected in approximately 17 and approximately 7% of JAK2V617F-positive and -negative cases, respectively (P=0.04). However, this apparent clustering of the two mutations was accounted for by an independent association between mutant TET2 and advanced age; mutational frequency was approximately 23% in patients > or =60 years old versus approximately 4% in younger patients (P<0.0001). The presence of mutant TET2 did not affect survival, leukemic transformation or thrombosis in either PV or PMF; a correlation with hemoglobin <10 g per 100 ml in PMF was noted (P=0.05). We conclude that TET2 mutations occur in both JAK2V617F-positive and -negative MPN, are more prevalent in older patients, display similar frequencies across MPN subcategories and disease stages, and hold limited prognostic relevance.

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    • "The presence of activating mutation V617F in Janus kinase 2 (JAK2) gene is a hallmark of MPN, since 97 % of PV patients and about 50 % of ET and PMF patients harbor this mutation (Baxter et al. 2005; James et al. 2005; Kralovics et al. 2005; Levine et al. 2005). Only a small portion of JAK2V617F-negative patients have other mutations , such as JAK2 exon 12 mutations (Scott et al. 2007), MPL exon 10 mutations (Pardanani et al. 2006; Beer et al. 2008), and mutations in CBL (Grand et al. 2009) and TET2 (Tefferi et al. 2009). There is strong evidence that mutations in these genes are decisive events that are responsible for the majority of biological and clinical features of MPN (Plo and Vainchenker 2009). "
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