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TET2 mutations and their clinical correlates in polycythemia vera, essential thrombocythemia and myelofibrosis
Open accessAbstract
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 ∼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 ∼16, 5, 17, 14, 14 and 17% (P=0.50). Mutant TET2 was detected in ∼17 and ∼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 ∼23% in patients ⩾60 years old versus ∼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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Cites
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Metadata
- Authors
- Tefferi, A., Pardanani, A., Lim, K.-H., Abdel-Wahab, O., Lasho, T. L., Patel, J., Gangat, N., Finke, C. M., Schwager, S., Mullally, A., Li, C.-Y., Hanson, C. A., Mesa, R., Bernard, O., Delhommeau, F., Vainchenker, W., Gilliland, D. G., & Levine, R. L.
- Venue
- Leukemia
- Published
- 2009-03-05
- Volume
- 23
- Issue
- 5
- Pages
- 905-911
- ISSN
- 0887-6924 (ISSN-L)
- 1476-5551
- OpenAlex
- W2112129429
- Cited by
- 425
- References
- 2
- FWCI
- 26.48
- Type
- journal article
- Language
- en
- Open access
- green
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