Genetic characterization of TET1, TET2, and TET3 alterations in myeloid malignancies

Omar Abdel-Wahab, Ann Mullally, Cyrus Hedvat, Guillermo Garcia-Manero, Jay Patel, Martha Wadleigh, Sebastien Malinge, Jin Juan Yao, Outi Kilpivaara, Rukhmi Bhat, Kety Huberman, Sabrena Thomas, Igor Dolgalev, Adriana Heguy, Elisabeth Paietta, Michelle M. Le Beau, Miloslav Beran, Martin S. Tallman, Benjamin L. Ebert, Hagop M. KantarjianRichard M. Stone, D. Gary Gilliland, John D. Crispino, Ross L. Levine

Research output: Contribution to journalArticle

473 Scopus citations

Abstract

Disease alleles that activate signal transduction are common in myeloid malignancies; however, there are additional unidentified mutations that contribute to myeloid transformation. Based on the recent identification of TET2 mutations, we evaluated the mutational status of TET1, TET2, and TET3 in myeloproliferative neoplasms (MPNs), chronic myelomonocytic leukemia (CMML), and acute myeloid leukemia (AML). Sequencing of TET2 in 408 paired tumor/normal samples distinguished between 68 somatic mutations and 6 novel single nucleotide polymorphisms and identified TET2 mutations in MPN (27 of 354, 7.6%), CMML (29 of 69, 42%), AML (11 of 91, 12%), and M7 AML (1 of 28, 3.6%) samples.We did not identify somatic TET1 or TET3 mutations or TET2 promoter hypermethylation in MPNs. TET2 mutations did not cluster in genetically defined MPN, CMML, or AML subsets but were associated with decreased overall survival in AML (P = .029). These data indicate that TET2 mutations are observed in different myeloid malignancies and may be important in AML prognosis.

Original languageEnglish (US)
Pages (from-to)144-147
Number of pages4
JournalBlood
Volume114
Issue number1
DOIs
StatePublished - 2009

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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  • Cite this

    Abdel-Wahab, O., Mullally, A., Hedvat, C., Garcia-Manero, G., Patel, J., Wadleigh, M., Malinge, S., Yao, J. J., Kilpivaara, O., Bhat, R., Huberman, K., Thomas, S., Dolgalev, I., Heguy, A., Paietta, E., Le Beau, M. M., Beran, M., Tallman, M. S., Ebert, B. L., ... Levine, R. L. (2009). Genetic characterization of TET1, TET2, and TET3 alterations in myeloid malignancies. Blood, 114(1), 144-147. https://doi.org/10.1182/blood-2009-03-210039