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, JinJuan Yao, Outi Kilpivaara, Rukhmi Bhat, Kety Huberman, Sabrena Thomas, Igor Dolgalev, Adriana Heguy, Elisabeth M. Paietta, Michelle M. Le Beau, Miloslav Beran, Martin S. Tallman, Benjamin L. Ebert, Hagop M. Kantarjian & 4 others Richard M. Stone, D. Gary Gilliland, John D. Crispino, Ross L. Levine

Research output: Contribution to journalArticle

444 Citations (Scopus)

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

Fingerprint

Signal transduction
Polymorphism
Tumors
Nucleotides
Acute Myeloid Leukemia
Mutation
Leukemia, Myelomonocytic, Chronic
Neoplasms
Leukemia, Megakaryoblastic, Acute
Single Nucleotide Polymorphism
Signal Transduction
Alleles

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Abdel-Wahab, O., Mullally, A., Hedvat, C., Garcia-Manero, G., Patel, J., Wadleigh, M., ... 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

Genetic characterization of TET1, TET2, and TET3 alterations in myeloid malignancies. / Abdel-Wahab, Omar; Mullally, Ann; Hedvat, Cyrus; Garcia-Manero, Guillermo; Patel, Jay; Wadleigh, Martha; Malinge, Sebastien; Yao, JinJuan; Kilpivaara, Outi; Bhat, Rukhmi; Huberman, Kety; Thomas, Sabrena; Dolgalev, Igor; Heguy, Adriana; Paietta, Elisabeth M.; Le Beau, Michelle M.; Beran, Miloslav; Tallman, Martin S.; Ebert, Benjamin L.; Kantarjian, Hagop M.; Stone, Richard M.; Gilliland, D. Gary; Crispino, John D.; Levine, Ross L.

In: Blood, Vol. 114, No. 1, 2009, p. 144-147.

Research output: Contribution to journalArticle

Abdel-Wahab, O, Mullally, A, Hedvat, C, Garcia-Manero, G, Patel, J, Wadleigh, M, Malinge, S, Yao, J, Kilpivaara, O, Bhat, R, Huberman, K, Thomas, S, Dolgalev, I, Heguy, A, Paietta, EM, Le Beau, MM, Beran, M, Tallman, MS, Ebert, BL, Kantarjian, HM, Stone, RM, Gilliland, DG, Crispino, JD & Levine, RL 2009, 'Genetic characterization of TET1, TET2, and TET3 alterations in myeloid malignancies', Blood, vol. 114, no. 1, pp. 144-147. https://doi.org/10.1182/blood-2009-03-210039
Abdel-Wahab O, Mullally A, Hedvat C, Garcia-Manero G, Patel J, Wadleigh M et al. Genetic characterization of TET1, TET2, and TET3 alterations in myeloid malignancies. Blood. 2009;114(1):144-147. https://doi.org/10.1182/blood-2009-03-210039
Abdel-Wahab, Omar ; Mullally, Ann ; Hedvat, Cyrus ; Garcia-Manero, Guillermo ; Patel, Jay ; Wadleigh, Martha ; Malinge, Sebastien ; Yao, JinJuan ; Kilpivaara, Outi ; Bhat, Rukhmi ; Huberman, Kety ; Thomas, Sabrena ; Dolgalev, Igor ; Heguy, Adriana ; Paietta, Elisabeth M. ; Le Beau, Michelle M. ; Beran, Miloslav ; Tallman, Martin S. ; Ebert, Benjamin L. ; Kantarjian, Hagop M. ; Stone, Richard M. ; Gilliland, D. Gary ; Crispino, John D. ; Levine, Ross L. / Genetic characterization of TET1, TET2, and TET3 alterations in myeloid malignancies. In: Blood. 2009 ; Vol. 114, No. 1. pp. 144-147.
@article{d0b0039e0f8848ed8e824bb6e50b4940,
title = "Genetic characterization of TET1, TET2, and TET3 alterations in myeloid malignancies",
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.",
author = "Omar Abdel-Wahab and Ann Mullally and Cyrus Hedvat and Guillermo Garcia-Manero and Jay Patel and Martha Wadleigh and Sebastien Malinge and JinJuan Yao and Outi Kilpivaara and Rukhmi Bhat and Kety Huberman and Sabrena Thomas and Igor Dolgalev and Adriana Heguy and Paietta, {Elisabeth M.} and {Le Beau}, {Michelle M.} and Miloslav Beran and Tallman, {Martin S.} and Ebert, {Benjamin L.} and Kantarjian, {Hagop M.} and Stone, {Richard M.} and Gilliland, {D. Gary} and Crispino, {John D.} and Levine, {Ross L.}",
year = "2009",
doi = "10.1182/blood-2009-03-210039",
language = "English (US)",
volume = "114",
pages = "144--147",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "1",

}

TY - JOUR

T1 - Genetic characterization of TET1, TET2, and TET3 alterations in myeloid malignancies

AU - Abdel-Wahab, Omar

AU - Mullally, Ann

AU - Hedvat, Cyrus

AU - Garcia-Manero, Guillermo

AU - Patel, Jay

AU - Wadleigh, Martha

AU - Malinge, Sebastien

AU - Yao, JinJuan

AU - Kilpivaara, Outi

AU - Bhat, Rukhmi

AU - Huberman, Kety

AU - Thomas, Sabrena

AU - Dolgalev, Igor

AU - Heguy, Adriana

AU - Paietta, Elisabeth M.

AU - Le Beau, Michelle M.

AU - Beran, Miloslav

AU - Tallman, Martin S.

AU - Ebert, Benjamin L.

AU - Kantarjian, Hagop M.

AU - Stone, Richard M.

AU - Gilliland, D. Gary

AU - Crispino, John D.

AU - Levine, Ross L.

PY - 2009

Y1 - 2009

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=67651065502&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67651065502&partnerID=8YFLogxK

U2 - 10.1182/blood-2009-03-210039

DO - 10.1182/blood-2009-03-210039

M3 - Article

VL - 114

SP - 144

EP - 147

JO - Blood

JF - Blood

SN - 0006-4971

IS - 1

ER -