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

Ayalew Tefferi, Animesh D Pardanani, K. H. Lim, O. Abdel-Wahab, T. L. Lasho, J. Patel, N. Gangat, C. M. Finke, S. Schwager, A. Mullally, C. Y. Li, C. A. Hanson, R. Mesa, O. Bernard, F. Delhommeau, W. Vainchenker, D. G. Gilliland, R. L. Levine

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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 ∼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 100ml 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.

Original languageEnglish (US)
Pages (from-to)905-911
Number of pages7
JournalLeukemia
Volume23
Issue number5
DOIs
StatePublished - 2009

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Essential Thrombocythemia
Polycythemia Vera
Primary Myelofibrosis
Mutation
Blast Crisis
Neoplasms
Frameshift Mutation
DNA Sequence Analysis
Cluster Analysis
Exons
Hemoglobins
Thrombosis
Bone Marrow
Survival
DNA

ASJC Scopus subject areas

  • Hematology
  • Cancer Research
  • Anesthesiology and Pain Medicine

Cite this

TET2 mutations and their clinical correlates in polycythemia vera, essential thrombocythemia and myelofibrosis. / Tefferi, Ayalew; Pardanani, Animesh D; 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.

In: Leukemia, Vol. 23, No. 5, 2009, p. 905-911.

Research output: Contribution to journalArticle

Tefferi, A, Pardanani, AD, Lim, KH, Abdel-Wahab, O, Lasho, TL, Patel, J, Gangat, N, Finke, CM, Schwager, S, Mullally, A, Li, CY, Hanson, CA, Mesa, R, Bernard, O, Delhommeau, F, Vainchenker, W, Gilliland, DG & Levine, RL 2009, 'TET2 mutations and their clinical correlates in polycythemia vera, essential thrombocythemia and myelofibrosis', Leukemia, vol. 23, no. 5, pp. 905-911. https://doi.org/10.1038/leu.2009.47
Tefferi, Ayalew ; Pardanani, Animesh D ; 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. / TET2 mutations and their clinical correlates in polycythemia vera, essential thrombocythemia and myelofibrosis. In: Leukemia. 2009 ; Vol. 23, No. 5. pp. 905-911.
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title = "TET2 mutations and their clinical correlates in polycythemia vera, essential thrombocythemia and myelofibrosis",
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 ∼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 100ml 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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T1 - TET2 mutations and their clinical correlates in polycythemia vera, essential thrombocythemia and myelofibrosis

AU - Tefferi, Ayalew

AU - Pardanani, Animesh D

AU - Lim, K. H.

AU - Abdel-Wahab, O.

AU - Lasho, T. L.

AU - Patel, J.

AU - Gangat, N.

AU - Finke, C. M.

AU - Schwager, S.

AU - Mullally, A.

AU - Li, C. Y.

AU - Hanson, C. A.

AU - Mesa, R.

AU - Bernard, O.

AU - Delhommeau, F.

AU - Vainchenker, W.

AU - Gilliland, D. G.

AU - Levine, R. L.

PY - 2009

Y1 - 2009

N2 - 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 100ml 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.

AB - 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 100ml 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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