ETV6 rearrangements are recurrent in myeloid malignancies and are frequently associated with other genetic events

Genes Chromosomes and Cancer

Volumn 51, Issue 4, 2012, Pages 328-337

  Haferlach, Claudia ^a   Bacher, Ulrike ^b   Schnittger, Susanne ^a   Alpermann, Tamara ^a   Zenger, Melanie ^a   Kern, Wolfgang ^a   Haferlach, Torsten ^a  

^a MLL MUNICH LEUKEMIA LABORATORY   (Germany)

^b UNIVERSITY OF HAMBURG   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

CD34 ANTIGEN; CD7 ANTIGEN; NUCLEOPHOSMIN; TRANSCRIPTION FACTOR ETV6; TRANSCRIPTION FACTOR RUNX1;

ACUTE GRANULOCYTIC LEUKEMIA; ADULT; AGED; ARTICLE; CANCER SURVIVAL; CHROMOSOME ABERRATION; CHROMOSOME BANDING PATTERN; CHRONIC MYELOMONOCYTIC LEUKEMIA; CONTROLLED STUDY; EVENT FREE SURVIVAL; FEMALE; FLUORESCENCE IN SITU HYBRIDIZATION; GENE MUTATION; GENE REARRANGEMENT; GENETIC ASSOCIATION; HUMAN; IMMUNOPHENOTYPING; MAJOR CLINICAL STUDY; MALE; MYELODYSPLASTIC SYNDROME; MYELOID LEUKEMIA; MYELOPROLIFERATIVE DISORDER; OVERALL SURVIVAL; PRIORITY JOURNAL; PROTEIN EXPRESSION;

ADULT; AGED; AGED, 80 AND OVER; ANTIGENS, CD34; ANTIGENS, CD7; CHROMOSOME BANDING; CORE BINDING FACTOR ALPHA 2 SUBUNIT; DISEASE-FREE SURVIVAL; FEMALE; GENE REARRANGEMENT; HUMANS; IMMUNOPHENOTYPING; IN SITU HYBRIDIZATION, FLUORESCENCE; KARYOTYPE; LEUKEMIA, MYELOID, ACUTE; MALE; MIDDLE AGED; MYELODYSPLASTIC SYNDROMES; MYELOPROLIFERATIVE DISORDERS; NUCLEAR PROTEINS; PROGNOSIS; PROTO-ONCOGENE PROTEINS C-ETS; REPRESSOR PROTEINS; YOUNG ADULT;

EID: 84856805875     PISSN: 10452257     EISSN: 10982264     Source Type: Journal    
DOI: 10.1002/gcc.21918     Document Type: Article

References (34)

1. Asou N, Iwanaga E, Nanri T, Mitsuya H. 2010. Successful treatment with low-dose imatinib mesylate of therapy-related myeloid neoplasm harboring TEL-PDGFRB in a patient with acute promyelocytic leukemia. Haematologica 95: e1.
2. Bacher U, Haferlach C, Kern W, Haferlach T, Schnittger S. 2008. Prognostic relevance of FLT3-TKD mutations in AML: The combination matters-An analysis of 3082 patients. Blood 111: 2527-2537.
3. Bain B, Gilliland DG, Horny H-P, Vardiman JW. 2008. Myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PGDFRA, PDGFRB or FGFR1. In: Swerdlow S, Campo E, Harris NL, Jaffe E, Pileri S, Stein H, Thiele J, Vardiman J, editors. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Lyon: International Agency for Research on Cancer (IARC), pp. 67-73.
4. Barjesteh van Waalwijk van Doorn-Khosrovani, Spensberger D, de Knegt Y, Tang M, Lowenberg B, Delwel R. 2005. Somatic heterozygous mutations in ETV6 (TEL) and frequent absence of ETV6 protein in acute myeloid leukemia. Oncogene 24: 4129-4137.
5. Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DA, Gralnick HR, Sultan C. 1985. Proposed revised criteria for the classification of acute myeloid leukemia. A report of the French-American-British Cooperative Group. Ann Intern Med 103: 620-625.
6. Büchner T, Berdel W, Haferlach C, Haferlach T, Schnittger S, Müller-Tidow C, Braess J, Spiekermann K, Kienast J, Staib P, Grüneisen A, Kern W, Reichle A, Maschmeyer G, Aul C, Lengfelder E, Sauerland MC, Heinecke A, Wörmann B, Hiddemann W. 2009. Age-related risk profile and chemotherapy dose response in acute myeloid leukemia: A Study by the German Acute Myeloid Leukemia Cooperative Group. J Clin Oncol 27: 61-69.
7. Chase A, Reiter A, Burci L, Cazzaniga G, Biondi A, Pickard J, Roberts IA, Goldman JM, Cross NC. 1999. Fusion of ETV6 to the caudal-related homeobox gene CDX2 in acute myeloid leukemia with the t(12;13)(p13;q12). Blood 93: 1025-1031.
8. Cools J, Bilhou-Nabera C, Wlodarska I, Cabrol C, Talmant P, Bernard P, Hagemeijer A, Marynen P. 1999. Fusion of a novel gene, BTL, to ETV6 in acute myeloid leukemias with a t(4;12)(q11-q12;p13). Blood 94: 1820-1824.
9. Cools J, Mentens N, Odero MD, Peeters P, Wlodarska I, Delforge M, Hagemeijer A, Marynen P. 2002. Evidence for position effects as a variant ETV6-mediated leukemogenic mechanism in myeloid leukemias with a t(4;12)(q11-q12;p13) or t(5;12)(q31;p13). Blood 99: 1776-1784.
10. Crescenzi B, La Starza R., Nozzoli C, Ciolli S, Matteucci C, Romoli S, Rigacci L, Gorello P, Bosi A, Martelli MF, Marynen P, Mecucci C. 2007. Molecular cytogenetic findings in a four-way t(1;12;5;12)(p36;p13;q33;q24) underlying the ETV6-PDGFRB fusion gene in chronic myelomonocytic leukemia. Cancer Genet Cytogenet 176: 67-71.
11. Erben P, Gosenca D, Müller M, Reinhard J, Score J, del Valle F, Walz C, Mix J, Metzgeroth G, Ernst T, Haferlach C, Cross N, Hochhaus A, Reiter A. 2010. Screening for diverse PDGFRA or PDGFRB fusion genes is facilitated by generic quantitative transcriptase polymerase chain reaction analysis. Haematologica 95: 738-744.
12. Golub TR, Barker GF, Lovett M, Gilliland DG. 1994. Fusion of PDGF receptor beta to a novel ets-like gene, tel, in chronic myelomonocytic leukemia with t(5;12) chromosomal translocation. Cell 77: 307-316.
13. Grimwade D, Hills R, Moorman AV, Walker H, Chatters S, Goldstone A, Wheatley K, Harrison C, Burnett A; on behalf of the National Cancer Research Institute Adult Leukaemia WorkingGroup. 2010. Refinement of cytogenetic classification in acute myeloid leukemia: Determination of prognostic significance of rare recurring chromosomal abnormalities amongst 5, 876 younger adult patients treated in the UK Medical Research Council trials. Blood 116: 354-365.
14. Harada H, Harada Y, Eguchi M, Dohy H, Kamada N. 1997. Characterization of acute leukemia with t(4;12). Leuk Lymphoma 25: 47-53.
15. Harrison CJ, Hills RK, Moorman AV, Grimwade DJ, Hann I, Webb DK, Wheatley K, de Graaf SS, van den Berg E, Burnett AK, Gibson BE. 2010. Cytogenetics of childhood acute myeloid leukemia: United Kingdom Medical Research Council Treatment trials AML 10 and 12. J Clin Oncol 28: 2674-2681.
16. Hiller B, Bradtke J, Balz H, Rieder H. 2005. CyDAS: A cytogenetic data analysis system. Bioinformatics 21: 1282-1283.
17. Huret JL. 2011. 12p13 rearrangements in treatment related leukemia. Atlas Genet Cytogenet Oncol Haematol. Available at
18. Kern W, Bacher U, Haferlach C, Schnittger S, Haferlach T. 2010. The role of multiparameter flow cytometry for disease monitoring in AML. Best Pract Res Clin Haematol 23: 379-390.
19. Löffler H, Raststetter J, Haferlach T. 2004. Atlas of Clinical Hematology. Berlin: Springer.
20. O'Connor HE, Butler TA, Clark R, Swanton S, Harrison CJ, Secker-Walker LM, Foroni L. 1998. Abnormalities of the ETV6 gene occur in the majority of patients with aberrations of the short arm of chromosome 12: A combined PCR and Southern blotting analysis. Leukemia 12: 1099-1106.
21. Odero MD, Carlson K, Calasanz MJ, Lahortiga I, Chinwalla V, Rowley JD. 2001. Identification of new translocations involving ETV6 in hematologic malignancies by fluorescence in situ hybridization and spectral karyotyping. Genes Chromosomes Cancer 31: 134-142.
22. Peeters P, Wlodarska I, Baens M, Criel A, Selleslag D, Hagemeijer A, van den Berghe H, Marynen P. 1997. Fusion of ETV6 to MDS/EVI1 as a result of t(3;12)(q26;p13) in myeloproliferative disorders. Cancer Res 57: 564-569.
23. Raynaud SD, Baens M, Grosgeorge J, Rodgers K, Reid CD, Dainton M, Dyer M, Fuzibet JG, Gratecos N, Taillan B, Ayraud N, Marynen P. 1996. Fluorescence in situ hybridization analysis of t(3; 12)(q26; p13): A recurring chromosomal abnormality involving the TEL gene (ETV6) in myelodysplastic syndromes. Blood 88: 682-689.
24. Rubnitz JE, Wichlan D, Devidas M, Shuster J, Linda SB, Kurtzberg J, Bell B, Hunger SP, Chauvenet A, Pui CH, Camitta B, Pullen J. 2008. Prospective analysis of TEL gene rearrangements in childhood acute lymphoblastic leukemia: A Children's Oncology Group study. J Clin Oncol 26: 2186-2191.
25. Schnittger S, Schoch C, Dugas M, Kern W, Staib P, Wuchter C, Löffler H, Sauerland CM, Serve H, Büchner T, Haferlach T, Hiddemann W. 2002. Analysis of FLT3 length mutations in 1003 patients with acute myeloid leukemia: Correlation to cytogenetics, FAB subtype, and prognosis in the AMLCG study and usefulness as a marker for the detection of minimal residual disease. Blood 100: 59-66.
26. Schnittger S, Schoch C, Kern W, Mecucci C, Tschulik C, Martelli MF, Haferlach T, Hiddemann W, Falini B. 2005. Nucleophosmin gene mutations are predictors of favorable prognosis in acute myelogenous leukemia with a normal karyotype. Blood 106: 3733-3739.
27. Schnittger S, Kern W, Tschulik C, Weiss T, Dicker F, Falini B, Haferlach C, Haferlach T. 2009. Minimal residual disease levels assessed by NPM1 mutation-specific RQ-PCR provide important prognostic information in AML. Blood 114: 2220-2231.
28. Schnittger S, Dicker F, Kern W, Wendland N, Sundermann J, Alpermann T, Haferlach C, Haferlach T. 2011. RUNX1 mutations are frequent in de novo AML with noncomplex karyotype and confer an unfavorable prognosis. Blood 117: 2348-2357.
29. Schoch C, Schnittger S, Bursch S, Gerstner D, Hochhaus A, Berger U, Hehlmann R, Hiddemann W, Haferlach T. 2002. Comparison of chromosome banding analysis, interphase- and hypermetaphase-FISH, qualitative and quantitative PCR for diagnosis and for follow-up in chronic myeloid leukemia: A study on 350 cases. Leukemia 16: 53-59.
30. Slater RM, von Drunen E, Kroes WG, Weghuis DO, Van den Berg E, Smit EM, Van der Does-van den Berg A, van Wering E, Hahlen K, Carroll AJ, Raimondi SC, Beverloo HB. 2001. t(7;12)(q36;p13) and t(7;12)(q32;p13)-Translocations involving ETV6 in children 18 months of age or younger with myeloid disorders. Leukemia 15: 915-920.
31. Voutsadakis IA, Maillard N. 2003. Acute myelogenous leukemia with the t(3;12)(q26;p13) translocation: Case report and review of the literature. Am J Hematol 72: 135-137.
32. Walz C, Metzgeroth G, Haferlach C, Schmitt-Graeff A, Fabarius A, Hagen V, Prümmer O, Rauh S, Hehlmann R, Hochhaus A, Cross NC, Reiter A. 2007. Characterization of three new imatinib-responsive fusion genes in chronic myeloproliferative disorders generated by disruption of the platelet-derived growth factor receptor beta gene. Haematologica 92: 163-169.
33. Weisser M, Kern W, Schoch C, Hiddemann W, Haferlach T, Schnittger S. 2005. Risk assessment by monitoring expression levels of partial tandem duplications in the MLL gene in acute myeloid leukemia during therapy. Haematologica 90: 881-889.
34. Zuna J, Zaliova M, Muzikova K, Meyer C, Lizcova L, Zemanova Z, Brezinova J, Votava F, Marschalek R, Stary J, Trka J. 2010. Acute leukemias with ETV6/ABL1 (TEL/ABL) fusion: Poor prognosis and prenatal origin. Genes Chromosomes Cancer 49: 873-884.