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Gene Review

ETV6  -  ets variant 6

Homo sapiens

 
 
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Disease relevance of ETV6

 

Psychiatry related information on ETV6

  • METHOD: The study was conducted at three adolescent psychiatric departments in two mental health centers in the Tel Aviv area [5].
  • To summarize our 10-year experience with autistic children at the Tel Aviv Child Development Center, the files of all 55 children with autism treated at our center over a 10-year period were retrospectively reviewed [6].
  • Matched population samples from this kibbutz and the city of Tel Aviv revealed significant differences in dietary habits [7].
  • The center serves the Tel Aviv area for a variety of developmental disabilities [8].
  • A joint intake interview questionnaire and a dental anxiety scale explored the level, background and concomitant factors of dental anxiety among patients at the Universities of Tel Aviv (Israel), Goteborg (Sweden), and Pittsburgh (USA) [9].
 

High impact information on ETV6

 

Chemical compound and disease context of ETV6

 

Biological context of ETV6

  • Our results also indicate that the transactivation characteristics of ETV6/CBFA2 are a combination of positive and negative regulatory properties [17].
  • The ETV6 gene (also known as TEL) is the main target of chromosomal translocations affecting chromosome band 12p13 [18].
  • The ETV6 gene (first identified as TEL) is a frequent target of chromosomal translocations in both myeloid and lymphoid leukemias [3].
  • Hybridization with cosmid probes showed that the ETV6 gene was rearranged in this translocation [19].
  • Our results indicate that, besides the generation of fusion transcripts, deregulation of the expression of oncogenes could be a variant leukemogenic mechanism for translocations involving the 5' end of ETV6, especially for those translocations lacking functionally significant fusion transcripts [3].
 

Anatomical context of ETV6

 

Associations of ETV6 with chemical compounds

 

Physical interactions of ETV6

  • Molecular cytogenetic analysis confirmed that formation of an ETV6/ABL1 fusion in these patients required at least three chromosomal breaks and showed that each of these translocations is the result of a complex chromosomal rearrangement [30].
  • Our studies show that UBC9 binds to TEL exclusively through the HLH domain of TEL [31].
  • We found that H-L(3)MBT binds in vivo to TEL, and we have mapped the region of interaction to their respective SPM/SAM domains [32].
  • This is the first report of a complex cytogenetic clone, in association with an ETV6/AML1 fusion, developing in utero [33].
  • The ets family member Tel binds to the Fli-1 oncoprotein and inhibits its transcriptional activity [34].
 

Enzymatic interactions of ETV6

 

Regulatory relationships of ETV6

  • It appears that loss of TEL function activates a pathway that cooperates with TEL/RUNX1 and sequesters coactivator(s) into nonfunctional complex in the cytoplasm thus inhibiting transcription of target genes [38].
  • Although both proteins are transcriptional inhibitors binding similar DNA recognition sequences, they have opposite biologic effects: TEL inhibits proliferation while TEL2 promotes it [39].
  • Confirming these results, overexpression of TEL repressed Stat3 transcriptional activity [40].
  • The v-SRC-induced nucleo-cytoplasmic delocalization of TEL-M1 does not involve phosphorylation of the SRCD and does not require TEL self-association and repressive domains [41].
  • The rearrangement might also modify the regulation of BAZ2A by either activating a cryptic promoter or by coming under the control of the ETV6 promoter [42].
 

Other interactions of ETV6

 

Analytical, diagnostic and therapeutic context of ETV6

References

  1. A novel ETV6-NTRK3 gene fusion in congenital fibrosarcoma. Knezevich, S.R., McFadden, D.E., Tao, W., Lim, J.F., Sorensen, P.H. Nat. Genet. (1998) [Pubmed]
  2. 12p abnormalities and the TEL gene (ETV6) in childhood acute lymphoblastic leukemia. Raimondi, S.C., Shurtleff, S.A., Downing, J.R., Rubnitz, J., Mathew, S., Hancock, M., Pui, C.H., Rivera, G.K., Grosveld, G.C., Behm, F.G. Blood (1997) [Pubmed]
  3. 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). Cools, J., Mentens, N., Odero, M.D., Peeters, P., Wlodarska, I., Delforge, M., Hagemeijer, A., Marynen, P. Blood (2002) [Pubmed]
  4. Heterogeneity in the breakpoints in balanced rearrangements involving band 12p13 in hematologic malignancies identified by fluorescence in situ hybridization: TEL (ETV6 ) is involved in only one half. Sato, Y., Bohlander, S.K., Kobayashi, H., Reshmi, S., Suto, Y., Davis, E.M., Espinosa, R., Hoopes, R., Montgomery, K.T., Kucherlapati, R.S., Le Beau, M.M., Rowley, J.D. Blood (1997) [Pubmed]
  5. Weight gain associated with olanzapine and risperidone in adolescent patients: a comparative prospective study. Ratzoni, G., Gothelf, D., Brand-Gothelf, A., Reidman, J., Kikinzon, L., Gal, G., Phillip, M., Apter, A., Weizman, R. Journal of the American Academy of Child and Adolescent Psychiatry. (2002) [Pubmed]
  6. Characterization and comparison of autistic subgroups: 10 years' experience with autistic children. Fattal-Valevski, A., Kramer, U., Leitner, Y., Nevo, Y., Greenstein, Y., Harel, S. Developmental medicine and child neurology. (1999) [Pubmed]
  7. The low incidence of colorectal cancer in a "high-risk" population: its correlation with dietary habits. Rozen, P., Hellerstein, S.M., Horwitz, C. Cancer (1981) [Pubmed]
  8. Unprovoked seizures and developmental disabilities: clinical characteristics of children referred to a child development center. Nevo, Y., Shinnar, S., Samuel, E., Kramer, U., Leitner, Y., Fatal, A., Kutai, M., Harel, S. Pediatric neurology. (1995) [Pubmed]
  9. Characteristics of adult dentally fearful individuals. A cross-cultural study. Berggren, U., Pierce, C.J., Eli, I. Eur. J. Oral Sci. (2000) [Pubmed]
  10. A TEL-JAK2 fusion protein with constitutive kinase activity in human leukemia. Lacronique, V., Boureux, A., Valle, V.D., Poirel, H., Quang, C.T., Mauchauffé, M., Berthou, C., Lessard, M., Berger, R., Ghysdael, J., Bernard, O.A. Science (1997) [Pubmed]
  11. The TEL/ETV6 gene is required specifically for hematopoiesis in the bone marrow. Wang, L.C., Swat, W., Fujiwara, Y., Davidson, L., Visvader, J., Kuo, F., Alt, F.W., Gilliland, D.G., Golub, T.R., Orkin, S.H. Genes Dev. (1998) [Pubmed]
  12. N- and C-terminal isoforms of Arg quantified by real-time PCR are specifically expressed in human normal and neoplastic cells, in neoplastic cell lines, and in HL-60 cell differentiation. Perego, R.A., Corizzato, M., Bianchi, C., Eroini, B., Bosari, S. Mol. Carcinog. (2005) [Pubmed]
  13. A fluorescence in situ hybridization study of ETV6-NTRK3 fusion gene in secretory breast carcinoma. Makretsov, N., He, M., Hayes, M., Chia, S., Horsman, D.E., Sorensen, P.H., Huntsman, D.G. Genes Chromosomes Cancer (2004) [Pubmed]
  14. Clinical and genetic studies of ETV6/ABL1-positive chronic myeloid leukaemia in blast crisis treated with imatinib mesylate. Barbouti, A., Ahlgren, T., Johansson, B., Höglund, M., Lassen, C., Turesson, I., Mitelman, F., Fioretos, T. Br. J. Haematol. (2003) [Pubmed]
  15. Acute lymphoblastic leukemia with TEL-AML1 fusion has lower expression of genes involved in purine metabolism and lower de novo purine synthesis. Zaza, G., Yang, W., Kager, L., Cheok, M., Downing, J., Pui, C.H., Cheng, C., Relling, M.V., Evans, W.E. Blood (2004) [Pubmed]
  16. Detection of dual TEL-ABL transcripts and a Tel-Abl protein containing phosphotyrosine in a chronic myeloid leukemia patient. Lin, H., Guo, J.Q., Andreeff, M., Arlinghaus, R.B. Leukemia (2002) [Pubmed]
  17. Functional characterization of ETV6 and ETV6/CBFA2 in the regulation of the MCSFR proximal promoter. Fears, S., Gavin, M., Zhang, D.E., Hetherington, C., Ben-David, Y., Rowley, J.D., Nucifora, G. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  18. Fusion of a novel gene, BTL, to ETV6 in acute myeloid leukemias with a t(4;12)(q11-q12;p13). Cools, J., Bilhou-Nabera, C., Wlodarska, I., Cabrol, C., Talmant, P., Bernard, P., Hagemeijer, A., Marynen, P. Blood (1999) [Pubmed]
  19. Fusion of ETV6 to neurotrophin-3 receptor TRKC in acute myeloid leukemia with t(12;15)(p13;q25). Eguchi, M., Eguchi-Ishimae, M., Tojo, A., Morishita, K., Suzuki, K., Sato, Y., Kudoh, S., Tanaka, K., Setoyama, M., Nagamura, F., Asano, S., Kamada, N. Blood (1999) [Pubmed]
  20. Ectopic expression of the homeobox gene Cdx2 is the transforming event in a mouse model of t(12;13)(p13;q12) acute myeloid leukemia. Rawat, V.P., Cusan, M., Deshpande, A., Hiddemann, W., Quintanilla-Martinez, L., Humphries, R.K., Bohlander, S.K., Feuring-Buske, M., Buske, C. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  21. Breakage and fusion of the TEL (ETV6) gene in immature B lymphocytes induced by apoptogenic signals. Eguchi-Ishimae, M., Eguchi, M., Ishii, E., Miyazaki, S., Ueda, K., Kamada, N., Mizutani, S. Blood (2001) [Pubmed]
  22. A new ETV6/TEL partner gene, ARG (ABL-related gene or ABL2), identified in an AML-M3 cell line with a t(1;12)(q25;p13) translocation. Iijima, Y., Ito, T., Oikawa, T., Eguchi, M., Eguchi-Ishimae, M., Kamada, N., Kishi, K., Asano, S., Sakaki, Y., Sato, Y. Blood (2000) [Pubmed]
  23. Fusion of ETV6 to fibroblast growth factor receptor 3 in peripheral T-cell lymphoma with a t(4;12)(p16;p13) chromosomal translocation. Yagasaki, F., Wakao, D., Yokoyama, Y., Uchida, Y., Murohashi, I., Kayano, H., Taniwaki, M., Matsuda, A., Bessho, M. Cancer Res. (2001) [Pubmed]
  24. The identification of (ETV6)/RUNX1-regulated genes in lymphopoiesis using histone deacetylase inhibitors in ETV6/RUNX1-positive lymphoid leukemic cells. Starkova, J., Madzo, J., Cario, G., Kalina, T., Ford, A., Zaliova, M., Hrusak, O., Trka, J. Clin. Cancer Res. (2007) [Pubmed]
  25. The tyrosine kinase abl-related gene ARG is fused to ETV6 in an AML-M4Eo patient with a t(1;12)(q25;p13): molecular cloning of both reciprocal transcripts. Cazzaniga, G., Tosi, S., Aloisi, A., Giudici, G., Daniotti, M., Pioltelli, P., Kearney, L., Biondi, A. Blood (1999) [Pubmed]
  26. Suppression of ARG kinase activity by STI571 induces cell cycle arrest through up-regulation of CDK inhibitor p18/INK4c. Nishimura, N., Furukawa, Y., Sutheesophon, K., Nakamura, M., Kishi, K., Okuda, K., Sato, Y., Kano, Y. Oncogene (2003) [Pubmed]
  27. Congenital-infantile fibrosarcoma. A clinicopathologic study of 10 cases and molecular detection of the ETV6-NTRK3 fusion transcripts using paraffin-embedded tissues. Sheng, W.Q., Hisaoka, M., Okamoto, S., Tanaka, A., Meis-Kindblom, J.M., Kindblom, L.G., Ishida, T., Nojima, T., Hashimoto, H. Am. J. Clin. Pathol. (2001) [Pubmed]
  28. Transient response to imatinib mesylate (STI571) in a patient with the ETV6-ABL t(9;12) translocation. O'Brien, S.G., Vieira, S.A., Connors, S., Bown, N., Chang, J., Capdeville, R., Melo, J.V. Blood (2002) [Pubmed]
  29. ETV6-AML1 translocation breakpoints cluster near a purine/pyrimidine repeat region in the ETV6 gene. Thandla, S.P., Ploski, J.E., Raza-Egilmez, S.Z., Chhalliyil, P.P., Block, A.W., de Jong, P.J., Aplan, P.D. Blood (1999) [Pubmed]
  30. Molecular cytogenetic and clinical findings in ETV6/ABL1-positive leukemia. Van Limbergen, H., Beverloo, H.B., van Drunen, E., Janssens, A., Hählen, K., Poppe, B., Van Roy, N., Marynen, P., De Paepe, A., Slater, R., Speleman, F. Genes Chromosomes Cancer (2001) [Pubmed]
  31. Modulation of TEL transcription activity by interaction with the ubiquitin-conjugating enzyme UBC9. Chakrabarti, S.R., Sood, R., Ganguly, S., Bohlander, S., Shen, Z., Nucifora, G. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  32. The human L(3)MBT polycomb group protein is a transcriptional repressor and interacts physically and functionally with TEL (ETV6). Boccuni, P., MacGrogan, D., Scandura, J.M., Nimer, S.D. J. Biol. Chem. (2003) [Pubmed]
  33. Complex chromosomal abnormalities in utero, 5 years before leukaemia. Broadfield, Z.J., Hain, R.D., Harrison, C.J., Reza Jalali, G., McKinley, M., Michalová, K., Robinson, H.M., Zemanová, Z., Martineau, M. Br. J. Haematol. (2004) [Pubmed]
  34. The ets family member Tel binds to the Fli-1 oncoprotein and inhibits its transcriptional activity. Kwiatkowski, B.A., Bastian, L.S., Bauer, T.R., Tsai, S., Zielinska-Kwiatkowska, A.G., Hickstein, D.D. J. Biol. Chem. (1998) [Pubmed]
  35. The second ETV6 allele is not necessarily deleted in acute leukemias with a ETV6/ABL fusion. Hannemann, J.R., Healy, L.E., Ridge, S.A., Wiedemann, L.M. Genes Chromosomes Cancer (1998) [Pubmed]
  36. Expression profile of wild-type ETV6 in childhood acute leukaemia. Patel, N., Goff, L.K., Clark, T., Ford, A.M., Foot, N., Lillington, D., Hing, S., Pritchard-Jones, K., Jones, L.K., Saha, V. Br. J. Haematol. (2003) [Pubmed]
  37. The leukaemic oncoproteins Bcr-Abl and Tel-Abl (ETV6/Abl) have altered substrate preferences and activate similar intracellular signalling pathways. Voss, J., Posern, G., Hannemann, J.R., Wiedemann, L.M., Turhan, A.G., Poirel, H., Bernard, O.A., Adermann, K., Kardinal, C., Feller, S.M. Oncogene (2000) [Pubmed]
  38. Mechanism of transcriptional repression by TEL/RUNX1 fusion protein. Lee, Y.J., Kim, J.H., Bae, S., Rho, S.K., Choe, S.Y. Mol. Cells (2004) [Pubmed]
  39. The ETS factor TEL2 is a hematopoietic oncoprotein. Carella, C., Potter, M., Bonten, J., Rehg, J.E., Neale, G., Grosveld, G.C. Blood (2006) [Pubmed]
  40. TEL/ETV6 is a signal transducer and activator of transcription 3 (Stat3)-induced repressor of Stat3 activity. Schick, N., Oakeley, E.J., Hynes, N.E., Badache, A. J. Biol. Chem. (2004) [Pubmed]
  41. v-SRC specifically regulates the nucleo-cytoplasmic delocalization of the major isoform of TEL (ETV6). Lopez, R.G., Carron, C., Ghysdael, J. J. Biol. Chem. (2003) [Pubmed]
  42. Fusion of ETV6 with an intronic sequence of the BAZ2A gene in a paediatric pre-B acute lymphoblastic leukaemia with a cryptic chromosome 12 rearrangement. Panagopoulos, I., Strömbeck, B., Isaksson, M., Heldrup, J., Olofsson, T., Johansson, B. Br. J. Haematol. (2006) [Pubmed]
  43. Fusion of TEL, the ETS-variant gene 6 (ETV6), to the receptor-associated kinase JAK2 as a result of t(9;12) in a lymphoid and t(9;15;12) in a myeloid leukemia. Peeters, P., Raynaud, S.D., Cools, J., Wlodarska, I., Grosgeorge, J., Philip, P., Monpoux, F., Van Rompaey, L., Baens, M., Van den Berghe, H., Marynen, P. Blood (1997) [Pubmed]
  44. Biallelic alterations of both ETV6 and CDKN1B genes in a t(12;21) childhood acute lymphoblastic leukemia case. Wlodarska, I., Baens, M., Peeters, P., Aerssens, J., Mecucci, C., Brock, P., Marynen, P., Van den Berghe, H. Cancer Res. (1996) [Pubmed]
  45. Fusion of ETV6 to MDS1/EVI1 as a result of t(3;12)(q26;p13) in myeloproliferative disorders. Peeters, P., Wlodarska, I., Baens, M., Criel, A., Selleslag, D., Hagemeijer, A., Van den Berghe, H., Marynen, P. Cancer Res. (1997) [Pubmed]
  46. ETV6-NCOA2: a novel fusion gene in acute leukemia associated with coexpression of T-lymphoid and myeloid markers and frequent NOTCH1 mutations. Strehl, S., Nebral, K., König, M., Harbott, J., Strobl, H., Ratei, R., Struski, S., Bielorai, B., Lessard, M., Zimmermann, M., Haas, O.A., Izraeli, S. Clin. Cancer Res. (2008) [Pubmed]
  47. Reappraisal of the clinical and biologic significance of myeloid-associated antigen expression in childhood acute lymphoblastic leukemia. Pui, C.H., Rubnitz, J.E., Hancock, M.L., Downing, J.R., Raimondi, S.C., Rivera, G.K., Sandlund, J.T., Ribeiro, R.C., Head, D.R., Relling, M.V., Evans, W.E., Behm, F.G. J. Clin. Oncol. (1998) [Pubmed]
 
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