nach oben

Current Hematologic Malignancy Reports

Erschienen in:

01.03.2012 | Myeloproliferative Neoplasms (JJ Kiladjian, Section Editor)

Role of TET2 Mutations in Myeloproliferative Neoplasms

verfasst von: Elodie Pronier, François Delhommeau

Erschienen in: Current Hematologic Malignancy Reports | Ausgabe 1/2012

Einloggen, um Zugang zu erhalten

Abstract

Recently, 5-hydroxymethylcytosine (5-hmC), the 6th base of DNA, was discovered as the product of the hydroxylation of 5-methylcytosine (5-mC) by the ten-eleven translocation (TET) oncogene family members. One of them, TET oncogene family member 2 (TET2), is mutated in a variety of myeloid malignancies, including in 15% of myeloproliferative neoplasms (MPNs). Recent studies tried to go further into the biological and epigenetic function of TET2 protein and 5-hmC marks in the pathogenesis of myeloid malignancies. Although its precise function remains partially unknown, TET2 appears to be an important regulator of hematopoietic stem cell biology. In both mouse and human cells, its inactivation leads to a dramatic deregulation of hematopoiesis that ultimately triggers blood malignancies. Understanding this leukemogenic process will provide tools to develop new epigenetic therapies against blood cancers.

Feinberg AP, Tycko B. The history of cancer epigenetics. Nat Rev Cancer. 2004;4:143–53.PubMedCrossRef

Jones PA, Laird PW. Cancer epigenetics comes of age. Nat Genet. 1999;21:163–7.PubMedCrossRef

Bird A. The essentials of DNA methylation. Cell. 1992;70:5–8.PubMedCrossRef

Kass SU, Pruss D, Wolffe AP. How does DNA methylation repress transcription? Trends Genet. 1997;13:444–9.PubMedCrossRef

Siegfried Z, Cedar H. DNA methylation: A molecular lock. Curr Biol. 1997;7:R305–7.PubMedCrossRef

Kriaucionis S, Heintz N. The nuclear DNA base 5-hydroxymethylcytosine is present in Purkinje neurons and the brain. Science. 2009;324:929–30.PubMedCrossRef

•• Tahiliani M, Koh KP, Shen Y, et al.: Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science 2009;324:930–935. Discovery of TET1 catalytic activity by homology with the trypanosome enzymes JBP1 and JBP2. Tahiliani et al. demonstrate for the first time the ability of a mammalian dioxygenase to convert 5-mC into 5-hmC. PubMedCrossRef

Lorsbach RB, Moore J, Mathew S, et al. Tet1, a member of a novel protein family, is fused to mll in acute myeloid leukemia containing the t(10;11)(q22;q23). Leukemia. 2003;17:637–41.PubMedCrossRef

• Ito S, D’Alessio AC, Taranova OV, et al.: Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification. Nature 2010;466:1129–1133. Ito et al. show that Tet1, Tet2, and Tet3 share the same catalytic activity and play a role in the transcription control of development genes. PubMedCrossRef

10.

•• Delhommeau F, Dupont S, Della Valle V, et al.: Mutation in TET2 in myeloid cancers. N Engl J Med 2009;360:2289–2301. First evidence for mutations in TET2 in myeloid malignancies, including MPN. Shows a selective advantage of TET2 mutant cells over TET2 wild-type cells in severe combined immunodeficiency repopulation assays. PubMedCrossRef

11.

•• Langemeijer SM, Kuiper RP, Berends M, et al.: Acquired mutations in TET2 are common in myelodysplastic syndromes. Nat Genet 2009;41:838–842. Large study of TET2 mutations in MDS and TET2 expression studies. Evidence for the modulation of TET2 during granulocytic differentiation. PubMedCrossRef

12.

Tefferi A, Levine RL, Lim KH, et al. Frequent TET2 mutations in systemic mastocytosis: clinical, KITD816V and FIP1L1-PDGFRA correlates. Leukemia. 2009;23:900–4.PubMedCrossRef

13.

Tefferi A, Lim KH, Abdel-Wahab O, et al. Detection of mutant TET2 in myeloid malignancies other than myeloproliferative neoplasms: CMML, MDS, MDS/MPN and AML. Leukemia. 2009;23:1343–5.PubMedCrossRef

14.

Tefferi A, Pardanani A, Lim KH, et al. Tet2 mutations and their clinical correlates in polycythemia vera, essential thrombocythemia and myelofibrosis. Leukemia. 2009;23:905–11.PubMedCrossRef

15.

•• Ko M, Huang Y, Jankowska AM, et al.: Impaired hydroxylation of 5-methylcytosine in myeloid cancers with mutant tet2. Nature 2010;468:839–843. Evidence that patients with TET2 mutations have low 5-hmC levels and an abnormal DNA methylation profile. PubMedCrossRef

16.

Vardiman JW, Thiele J, Arber DA, et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood. 2009;114:937–51.PubMedCrossRef

17.

Vardiman JW. Chronic myelogenous leukemia, bcr-abl1+. Am J Clin Pathol. 2009;132:250–60.PubMedCrossRef

18.

Tefferi A, Vainchenker W. Myeloproliferative neoplasms: Molecular pathophysiology, essential clinical understanding, and treatment strategies. J Clin Oncol. 2010;29:573–82.CrossRef

19.

Baxter EJ, Scott LM, Campbell PJ, et al. Acquired mutation of the tyrosine kinase jak2 in human myeloproliferative disorders. Lancet. 2005;365:1054–61.PubMed

20.

James C, Ugo V, Le Couedic JP, et al. A unique clonal jak2 mutation leading to constitutive signalling causes polycythaemia vera. Nature. 2005;434:1144–8.PubMedCrossRef

21.

Kralovics R, Passamonti F, Buser AS, et al. A gain-of-function mutation of jak2 in myeloproliferative disorders. N Engl J Med. 2005;352:1779–90.PubMedCrossRef

22.

Levine RL, Wadleigh M, Cools J, et al. Activating mutation in the tyrosine kinase jak2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. Cancer Cell. 2005;7:387–97.PubMedCrossRef

23.

Scott LM, Tong W, Levine RL, et al. Jak2 exon 12 mutations in polycythemia vera and idiopathic erythrocytosis. N Engl J Med. 2007;356:459–68.PubMedCrossRef

24.

Pardanani AD, Levine RL, Lasho T, et al. Mpl515 mutations in myeloproliferative and other myeloid disorders: a study of 1182 patients. Blood. 2006;108:3472–6.PubMedCrossRef

25.

Pikman Y, Lee BH, Mercher T, et al. Mplw515l is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia. PLoS Med. 2006;3:e270.PubMedCrossRef

26.

Jager R, Gisslinger H, Passamonti F, et al. Deletions of the transcription factor ikaros in myeloproliferative neoplasms. Leukemia. 2010;24:1290–8.PubMedCrossRef

27.

Oh ST, Simonds EF, Jones C, et al. Novel mutations in the inhibitory adaptor protein lnk drive JAK-STAT signaling in patients with myeloproliferative neoplasms. Blood. 2010;116:988–92.PubMedCrossRef

28.

Grand FH, Hidalgo-Curtis CE, Ernst T, et al. Frequent CBL mutations associated with 11q acquired uniparental disomy in myeloproliferative neoplasms. Blood. 2009;113:6182–92.PubMedCrossRef

29.

Green A, Beer P. Somatic mutations of IDH1 and IDH2 in the leukemic transformation of myeloproliferative neoplasms. N Engl J Med. 2010;362:369–70.PubMedCrossRef

30.

Ernst T, Chase AJ, Score J, et al. Inactivating mutations of the histone methyltransferase gene EZH2 in myeloid disorders. Nat Genet. 2010;42:722–6.PubMedCrossRef

31.

Carbuccia N, Murati A, Trouplin V, et al. Mutations of ASXL1 gene in myeloproliferative neoplasms. Leukemia. 2009;23:2183–6.PubMedCrossRef

32.

Abdel-Wahab O, Mullally A, Hedvat C, et al. Genetic characterization of TET1, TET2, and TET3 alterations in myeloid malignancies. Blood. 2009;114:144–7.PubMedCrossRef

33.

Viguie F, Aboura A, Bouscary D, et al. Common 4q24 deletion in four cases of hematopoietic malignancy: Early stem cell involvement? Leukemia. 2005;19:1411–5.PubMedCrossRef

34.

Makishima H, Jankowska AM, McDevitt MA, et al. CBL, CBLB, TET2, ASXL1, and IDH1/2 mutations and additional chromosomal aberrations constitute molecular events in chronic myelogenous leukemia. Blood. 2011;117:e198–206.PubMedCrossRef

35.

Roche-Lestienne C, Marceau A, Labis E, et al. Mutation analysis of TET2, IDH1, IDH2 and ASXL1 in chronic myeloid leukemia. Leukemia. 2011;25(10):1661–4.PubMedCrossRef

36.

Olcaydu D, Rumi E, Harutyunyan A, et al. The role of the JAK2 GGCC haplotype and the TET2 gene in familial myeloproliferative neoplasms. Haematologica. 2010;96:367–74.PubMedCrossRef

37.

Saint-Martin C, Leroy G, Delhommeau F, et al. Analysis of the ten-eleven translocation 2 (TET2) gene in familial myeloproliferative neoplasms. Blood. 2009;114:1628–32.PubMedCrossRef

38.

Schaub FX, Looser R, Li S, et al. Clonal analysis of TET2 and JAK2 mutations suggests that TET2 can be a late event in the progression of myeloproliferative neoplasms. Blood. 2010;115:2003–7.PubMedCrossRef

39.

Koh KP, Yabuuchi A, Rao S, et al. Tet1 and Tet2 regulate 5-hydroxymethylcytosine production and cell lineage specification in mouse embryonic stem cells. Cell Stem Cell. 2011;8:200–13.PubMedCrossRef

40.

Clouaire T, de Las Heras JI, Merusi C, Stancheva I. Recruitment of MBD1 to target genes requires sequence-specific interaction of the MBD domain with methylated DNA. Nucleic Acids Res. 2010;38:4620–34.PubMedCrossRef

41.

Nakao M, Matsui S, Yamamoto S, et al. Regulation of transcription and chromatin by methyl-CPG binding protein MBD1. Brain Dev. 2001;23 Suppl 1:S174–6.PubMedCrossRef

42.

Young SR, Skalnik DG. CXXC finger protein 1 is required for normal proliferation and differentiation of the PLB-985 myeloid cell line. DNA Cell Biol. 2007;26:80–90.PubMedCrossRef

43.

Dang L, White DW, Gross S, et al. Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature. 2009;462:739–44.PubMedCrossRef

44.

Ward PS, Patel J, Wise DR, et al. The common feature of leukemia-associated idh1 and idh2 mutations is a neomorphic enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate. Cancer Cell. 2010;17:225–34.PubMedCrossRef

45.

• Figueroa ME, Abdel-Wahab O, Lu C, et al.: Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation. Cancer Cell 2010;18:553–567. Evidence that IDH1/2 and TET2 mutations impair hematopoietic differentiation in a similar way. PubMedCrossRef

46.

Ito S, Shen L, Dai Q, et al. TET proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine. Science. 2011;333:1300–3.PubMedCrossRef

47.

• Pronier E, Almire C, Mokrani H, et al.: Inhibition of TET2-mediated conversion of 5-methylcytosine to 5-hydroxymethylcytosine disturbs erythroid and granulomonocytic differentiation of human hematopoietic progenitors. Blood 2011;118:2551–2555. Demonstration that MPN patients with TET2 mutations have low DNA contents of 5-hmC, and that TET2 depletion in human progenitors leads to abnormal myeloid differentiation. PubMedCrossRef

48.

Klose RJ, Bird AP. Genomic DNA methylation: the mark and its mediators. Trends Biochem Sci. 2006;31:89–97.PubMedCrossRef

49.

Penn NW, Suwalski R, O’Riley C, et al. The presence of 5-hydroxymethylcytosine in animal deoxyribonucleic acid. Biochem J. 1972;126:781–90.PubMed

50.

Li W, Liu M. Distribution of 5-hydroxymethylcytosine in different human tissues. J Nucleic Acids. 2011;2011:870726.PubMed

51.

Ficz G, Branco MR, Seisenberger S, et al. Dynamic regulation of 5-hydroxymethylcytosine in mouse ES cells and during differentiation. Nature. 2011;473:398–402.PubMedCrossRef

52.

Pastor WA, Pape UJ, Huang Y, et al. Genome-wide mapping of 5-hydroxymethylcytosine in embryonic stem cells. Nature. 2011;473:394–7.PubMedCrossRef

53.

Robertson J, Robertson AB, Klungland A. The presence of 5-hydroxymethylcytosine at the gene promoter and not in the gene body negatively regulates gene expression. Biochem Biophys Res Commun. 2011;411:40–3.PubMedCrossRef

54.

Stroud H, Feng S, Morey Kinney S, et al. 5-hydroxymethylcytosine is associated with enhancers and gene bodies in human embryonic stem cells. Genome Biol. 2011;12:R54.PubMedCrossRef

55.

Szulwach KE, Li X, Li Y, et al. Integrating 5-hydroxymethylcytosine into the epigenomic landscape of human embryonic stem cells. PLoS Genet. 2011;7:e1002154.PubMedCrossRef

56.

• Williams K, Christensen J, Pedersen MT, et al.: TET1 and hydroxymethylcytosine in transcription and DNA methylation fidelity. Nature 2011;473:343–348. Mapping of 5-hmC and TET1 localization: consequences for transcription and methylation. PubMedCrossRef

57.

Valinluck V, Sowers LC. Endogenous cytosine damage products alter the site selectivity of human DNA maintenance methyltransferase DNMT1. Cancer Res. 2007;67:946–50.PubMedCrossRef

58.

Jin SG, Kadam S, Pfeifer GP. Examination of the specificity of DNA methylation profiling techniques towards 5-methylcytosine and 5-hydroxymethylcytosine. Nucleic Acids Res. 2010;38:e125.PubMedCrossRef

59.

Guo JU, Su Y, Zhong C, et al. Hydroxylation of 5-methylcytosine by TET1 promotes active DNA demethylation in the adult brain. Cell. 2011;145:423–34.PubMedCrossRef

60.

Cortellino S, Xu J, Sannai M, et al. Thymine DNA glycosylase is essential for active DNA demethylation by linked deamination-base excision repair. Cell. 2011;146:67–79.PubMedCrossRef

61.

• Quivoron C, Couronne L, Della Valle V, et al.: Tet2 inactivation results in pleiotropic hematopoietic abnormalities in mouse and is a recurrent event during human lymphomagenesis. Cancer Cell 2011;20:25–38. Description of two Tet2 gene-disrupted mouse models with dramatic consequences on HSCs and both myeloid and lymphoid differentiations. First description of TET2 mutations in human B and T lymphomas. PubMedCrossRef

62.

Moran-Crusio K, Reavie L, Shih A, et al. Tet2 loss leads to increased hematopoietic stem cell self-renewal and myeloid transformation. Cancer Cell. 2011;20:11–24.PubMedCrossRef

63.

Li Z, Cai X, Cai CL, et al. Deletion of Tet2 in mice leads to dysregulated hematopoietic stem cells and subsequent development of myeloid malignancies. Blood. 2011;118(17):4509–18.PubMedCrossRef

64.

Ko M, Bandukwala HS, An J, et al. Ten-eleven-translocation 2 (tet2) negatively regulates homeostasis and differentiation of hematopoietic stem cells in mice. Proc Natl Acad Sci U S A. 2011;108:14566–71.PubMedCrossRef

65.

Chou WC, Chou SC, Liu CY, et al. TET2 mutation is an unfavorable prognostic factor in acute myeloid leukemia patients with intermediate-risk cytogenetics. Blood. 2011;118(14):3803–10.PubMedCrossRef

66.

Grossmann V, Kohlmann A, Eder C, et al. Molecular profiling of chronic myelomonocytic leukemia reveals diverse mutations in >80% of patients with TET2 and EZH2 being of high prognostic relevance. Leukemia. 2011;25:877–9.PubMedCrossRef

67.

Metzeler KH, Maharry K, Radmacher MD, et al. TET2 mutations improve the new European LeukemiaNet risk classification of acute myeloid leukemia: a Cancer And Leukemia Group B study. J Clin Oncol. 2011;29:1373–81.PubMedCrossRef

68.

Nibourel O, Kosmider O, Cheok M, et al. Incidence and prognostic value of TET2 alterations in de novo acute myeloid leukemia achieving complete remission. Blood. 2010;116:1132–5.PubMedCrossRef

69.

Shen Y, Zhu YM, Fan X, et al. Gene mutation patterns and their prognostic impact in a cohort of 1185 patients with acute myeloid leukemia. Blood. 2011;118(20):5593–603.PubMedCrossRef

70.

Smith AE, Mohamedali AM, Kulasekararaj A, et al. Next-generation sequencing of the TET2 gene in 355 MDS and CMML patients reveals low-abundance mutant clones with early origins, but indicates no definite prognostic value. Blood. 2010;116:3923–32.PubMedCrossRef

71.

Tefferi A. Mutational analysis in bcr-abl-negative classic myeloproliferative neoplasms: impact on prognosis and therapeutic choices. Leuk Lymphoma. 2010;51:576–82.PubMedCrossRef

72.

Abdel-Wahab O, Manshouri T, Patel J, et al. Genetic analysis of transforming events that convert chronic myeloproliferative neoplasms to leukemias. Cancer Res. 2010;70:447–52.PubMedCrossRef

73.

Beer PA, Delhommeau F, LeCouedic JP, et al. Two routes to leukemic transformation after a jak2 mutation-positive myeloproliferative neoplasm. Blood. 2010;115:2891–900.PubMedCrossRef

74.

Nguyen-Khac F, Lesty C, Eclache V, et al. Chromosomal abnormalities in transformed ph-negative myeloproliferative neoplasms are associated to the transformation subtype and independent of JAK2 and the TET2 mutations. Genes Chromosomes Cancer. 2010;49:919–27.PubMedCrossRef

75.

Vainchenker W, Delhommeau F, Constantinescu SN, Bernard OA. New mutations and pathogenesis of myeloproliferative neoplasms. Blood. 2011;118:1723–35.PubMedCrossRef

76.

Kiladjian JJ, Masse A, Cassinat B, et al. Clonal analysis of erythroid progenitors suggests that pegylated interferon alpha-2a treatment targets JAK2V617F clones without affecting TET2 mutant cells. Leukemia. 2010;24:1519–23.PubMedCrossRef

77.

Couronne L, Lippert E, Andrieux J, et al. Analyses of TET2 mutations in post-myeloproliferative neoplasm acute myeloid leukemias. Leukemia. 2010;24:201–3.PubMedCrossRef

Titel: Role of TET2 Mutations in Myeloproliferative Neoplasms
verfasst von: Elodie Pronier
François Delhommeau
Publikationsdatum: 01.03.2012
Verlag: Current Science Inc.
Erschienen in: Current Hematologic Malignancy Reports / Ausgabe 1/2012
Print ISSN: 1558-8211
Elektronische ISSN: 1558-822X
DOI: https://doi.org/10.1007/s11899-011-0108-8

Neu im Fachgebiet Onkologie

16.04.2024 | Maligne primäre ZNS-Tumoren | Nachrichten

Springer Medizin

Role of TET2 Mutations in Myeloproliferative Neoplasms

Abstract

Neu im Fachgebiet Onkologie

Manche Gestagene können das Risiko für Meningeome erhöhen

Einladung zum PSA-Screening senkt die Krebssterblichkeit

Chemotherapie mit Hindernissen

Das Ende der vollständigen axillären Lymphknotendissektion

Update Onkologie

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 1/2012

What Happened to Anti-CD33 Therapy for Acute Myeloid Leukemia?

Can Prognostic Factors Be Used to Direct Therapy in Chronic Lymphocytic Leukemia?

Transformation of a Chronic Myeloproliferative Neoplasm to Acute Myelogenous Leukemia: Does Anything Work?

Treatment of Older Patients with Chronic Lymphocytic Leukemia

Disordered Epigenetic Regulation in the Pathophysiology of Myeloproliferative Neoplasms

Management of Refractory Acute Myeloid Leukemia: Re-induction Therapy or Straight to Transplantation?

Neu im Fachgebiet Onkologie

Manche Gestagene können das Risiko für Meningeome erhöhen

Einladung zum PSA-Screening senkt die Krebssterblichkeit

Chemotherapie mit Hindernissen

Das Ende der vollständigen axillären Lymphknotendissektion

Update Onkologie