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Gene Review

MECOM  -  MDS1 and EVI1 complex locus

Homo sapiens

Synonyms: AML1-EVI-1, EVI1, MDS1, MDS1-EVI1, PRDM3
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Disease relevance of EVI1

  • The EVI1 gene, located at chromosome band 3q26, is overexpressed in some myeloid leukemia patients with breakpoints either 5' of the gene in the t(3;3)(q21;q26) or 3' of the gene in the inv(3)(q21q26) [1].
  • Two genes have been implicated in leukemias of patients with abnormalities of chromosome 3, band q26: EVI1, which can be activated over long distances by chromosomal rearrangements involving 3q26, and EAP, a ribosomal gene that fuses with AML1 in a therapy-related myelodysplasia patient with a t(3;21)(q26.2;q22) [2].
  • Fusion of ETV6 to MDS1/EVI1 as a result of t(3;12)(q26;p13) in myeloproliferative disorders [3].
  • Pronounced differences in the expression of the 5'-end variants were noted in response to all-trans retinoic acid: in a human teratocarcinoma cell line, only the EVI1 transcript variants containing alternative exons 1a and 1b were upregulated in response to this agent [4].
  • It should, therefore, be useful both for studying the biological characteristics of acute myelogenous leukemia M0 subtype and for investigating the role of the EVI1 gene in leukemogenesis [5].

High impact information on EVI1

  • Generation of the AML1-EVI-1 fusion gene in the t(3;21)(q26;q22) causes blastic crisis in chronic myelocytic leukemia [6].
  • Screening of a cDNA library of the t(3;21)-carrying leukemic cell line cells (SKH1) resulted in the isolation of two potentially complete AML1-EVI-1 chimeric cDNAs of 6 kb [6].
  • One result of this translocation is a fusion between the AML1, MDS1, and EVI1 genes, which encodes a transcription factor of approximately 200 kDa [7].
  • This murine model for AME-induced AML will help dissect the molecular mechanism of AML and the molecular biology of the AML1, MDS1, and EVI1 genes [7].
  • Intergenic splicing of MDS1 and EVI1 occurs in normal tissues as well as in myeloid leukemia and produces a new member of the PR domain family [1].

Chemical compound and disease context of EVI1


Biological context of EVI1

  • These results are important in view of the fact that EVI1 and MDS1 are involved in leukemia associated with chromosomal translocation breakpoints in the region between these genes [1].
  • In this report, we present evidence indicating that MDS1 exists in normal tissues both as a unique transcript and as a normal fusion transcript with EVI1, with an additional 188 codons at the 5' end of the previously reported EVI1 open reading frame [1].
  • The proto-oncogene EVI1 encodes a DNA binding protein and is located on chromosome 3q26 [9].
  • Furthermore, a comparison can be made with the formation of an AML1/MDS1/EVI1 fusion gene in translocations (3;21)(q26;q22) [3].
  • The resulting chimeric transcript consists of the first two exons of ETV6 fused to MDS1 sequences, which in turn is fused to the second exon of the EVI1 gene [3].

Anatomical context of EVI1


Associations of EVI1 with chemical compounds

  • Targeted Degradation of the AML1/MDS1/EVI1 Oncoprotein by Arsenic Trioxide [15].
  • Both low/high risk MDS may benefit significantly from therapy with ATO/thalidomide, and those with high pre-therapy EVI1 expression may be uniquely sensitive [8].

Regulatory relationships of EVI1


Other interactions of EVI1

  • The region of recurrent increase is approximately 30 Mb in extent, ranging from EVI1 to TFRC [17].
  • Taken together, these data support the hypothesis that the interaction with BRG1 is important for up-regulation of cell-growth by EVI1 [16].
  • When UT-7/GM cells were cultured with TPO, the level of EVI1 expression was increased, along with increased numbers of polynuclear megakaryocytes and expression of the platelet factor 4 (PF-4) gene [11].
  • Together, these data indicate that EVI1 activation is likely due not to the generation of a novel fusion gene with CDK6 but to a position effect dysregulating its transcriptional pattern [18].
  • The clustering was driven by the presence of chromosomal lesions (e.g., t(8;21), t(15;17), and inv(16)), particular genetic mutations (CEBPA), and abnormal oncogene expression (EVI1) [19].

Analytical, diagnostic and therapeutic context of EVI1


  1. Intergenic splicing of MDS1 and EVI1 occurs in normal tissues as well as in myeloid leukemia and produces a new member of the PR domain family. Fears, S., Mathieu, C., Zeleznik-Le, N., Huang, S., Rowley, J.D., Nucifora, G. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  2. Consistent intergenic splicing and production of multiple transcripts between AML1 at 21q22 and unrelated genes at 3q26 in (3;21)(q26;q22) translocations. Nucifora, G., Begy, C.R., Kobayashi, H., Roulston, D., Claxton, D., Pedersen-Bjergaard, J., Parganas, E., Ihle, J.N., Rowley, J.D. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  3. 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]
  4. Regulation of the expression of the oncogene EVI1 through the use of alternative mRNA 5'-ends. Aytekin, M., Vinatzer, U., Musteanu, M., Raynaud, S., Wieser, R. Gene (2005) [Pubmed]
  5. Establishment of an undifferentiated leukemia cell line (Kasumi-3) with t(3;7)(q27;q22) and activation of the EVI1 gene. Asou, H., Suzukawa, K., Kita, K., Nakase, K., Ueda, H., Morishita, K., Kamada, N. Jpn. J. Cancer Res. (1996) [Pubmed]
  6. Generation of the AML1-EVI-1 fusion gene in the t(3;21)(q26;q22) causes blastic crisis in chronic myelocytic leukemia. Mitani, K., Ogawa, S., Tanaka, T., Miyoshi, H., Kurokawa, M., Mano, H., Yazaki, Y., Ohki, M., Hirai, H. EMBO J. (1994) [Pubmed]
  7. Human AML1/MDS1/EVI1 fusion protein induces an acute myelogenous leukemia (AML) in mice: a model for human AML. Cuenco, G.M., Nucifora, G., Ren, R. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  8. Arsenic trioxide and thalidomide combination produces multi-lineage hematological responses in myelodysplastic syndromes patients, particularly in those with high pre-therapy EVI1 expression. Raza, A., Buonamici, S., Lisak, L., Tahir, S., Li, D., Imran, M., Chaudary, N.I., Pervaiz, H., Gallegos, J.A., Alvi, M.I., Mumtaz, M., Gezer, S., Venugopal, P., Reddy, P., Galili, N., Candoni, A., Singer, J., Nucifora, G. Leuk. Res. (2004) [Pubmed]
  9. High EVI1 expression predicts poor survival in acute myeloid leukemia: a study of 319 de novo AML patients. Barjesteh van Waalwijk van Doorn-Khosrovani, S., Erpelinck, C., van Putten, W.L., Valk, P.J., van der Poel-van de Luytgaarde, S., Hack, R., Slater, R., Smit, E.M., Beverloo, H.B., Verhoef, G., Verdonck, L.F., Ossenkoppele, G.J., Sonneveld, P., de Greef, G.E., Löwenberg, B., Delwel, R. Blood (2003) [Pubmed]
  10. Retroviral insertional activation of the EVI1 oncogene does not prevent G-CSF-induced maturation of the murine pluripotent myeloid cell line 32Dcl3. Khanna-Gupta, A., Lopingco, M.C., Savinelli, T., Zibello, T., Berliner, N., Perkins, A.S. Oncogene (1996) [Pubmed]
  11. EVI1 is expressed in megakaryocyte cell lineage and enforced expression of EVI1 in UT-7/GM cells induces megakaryocyte differentiation. Shimizu, S., Nagasawa, T., Katoh, O., Komatsu, N., Yokota, J., Morishita, K. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  12. Myeloid/natural killer cell blast crisis representing an additional translocation, t(3;7)(q26;q21) in Philadelphia-positive chronic myelogenous leukemia. Henzan, H., Yoshimoto, G., Okeda, A., Nagasaki, Y., Hirano, G., Takase, K., Tanimoto, T., Miyamoto, T., Fukuda, T., Nagafuji, K., Harada, M. Ann. Hematol. (2004) [Pubmed]
  13. Dysplastic definitive hematopoiesis in AML1/EVI1 knock-in embryos. Maki, K., Yamagata, T., Asai, T., Yamazaki, I., Oda, H., Hirai, H., Mitani, K. Blood (2005) [Pubmed]
  14. A novel variant of acute myelomonocytic leukemia carrying t(3;12)(q26;p13) with characteristics of 3q21q26 syndrome. Iwase, S., Furukawa, Y., Horiguchi-Yamada, J., Nemoto, T., Takahara, S., Kawano, T., Sekikawa, T., Ito, K., Yamazaki, Y., Kikuchi, J., Morishita, K., Yamada, H. Int. J. Hematol. (1998) [Pubmed]
  15. Targeted Degradation of the AML1/MDS1/EVI1 Oncoprotein by Arsenic Trioxide. Shackelford, D., Kenific, C., Blusztajn, A., Waxman, S., Ren, R. Cancer Res. (2006) [Pubmed]
  16. EVI1 promotes cell proliferation by interacting with BRG1 and blocking the repression of BRG1 on E2F1 activity. Chi, Y., Senyuk, V., Chakraborty, S., Nucifora, G. J. Biol. Chem. (2003) [Pubmed]
  17. Genomic copy number analysis of non-small cell lung cancer using array comparative genomic hybridization: implications of the phosphatidylinositol 3-kinase pathway. Massion, P.P., Kuo, W.L., Stokoe, D., Olshen, A.B., Treseler, P.A., Chin, K., Chen, C., Polikoff, D., Jain, A.N., Pinkel, D., Albertson, D.G., Jablons, D.M., Gray, J.W. Cancer Res. (2002) [Pubmed]
  18. A novel chromosomal translocation t(3;7)(q26;q21) in myeloid leukemia resulting in overexpression of EVI1. Storlazzi, C.T., Anelli, L., Albano, F., Zagaria, A., Ventura, M., Rocchi, M., Panagopoulos, I., Pannunzio, A., Ottaviani, E., Liso, V., Specchia, G. Ann. Hematol. (2004) [Pubmed]
  19. Prognostically useful gene-expression profiles in acute myeloid leukemia. Valk, P.J., Verhaak, R.G., Beijen, M.A., Erpelinck, C.A., Barjesteh van Waalwijk van Doorn-Khosrovani, S., Boer, J.M., Beverloo, H.B., Moorhouse, M.J., van der Spek, P.J., Löwenberg, B., Delwel, R. N. Engl. J. Med. (2004) [Pubmed]
  20. Interaction of EVI1 with cAMP-responsive element-binding protein-binding protein (CBP) and p300/CBP-associated factor (P/CAF) results in reversible acetylation of EVI1 and in co-localization in nuclear speckles. Chakraborty, S., Senyuk, V., Sitailo, S., Chi, Y., Nucifora, G. J. Biol. Chem. (2001) [Pubmed]
  21. DNA rearrangements proximal to the EVI1 locus associated with the 3q21q26 syndrome. Levy, E.R., Parganas, E., Morishita, K., Fichelson, S., James, L., Oscier, D., Gisselbrecht, S., Ihle, J.N., Buckle, V.J. Blood (1994) [Pubmed]
  22. Identification of binding sites of EVI1 in mammalian cells. Yatsula, B., Lin, S., Read, A.J., Poholek, A., Yates, K., Yue, D., Hui, P., Perkins, A.S. J. Biol. Chem. (2005) [Pubmed]
  23. Activation of EVI1 transcripts with chromosomal translocation joining the TCRVbeta locus and the EVI1 gene in human acute undifferentiated leukemia cell line (Kasumi-3) with a complex translocation of der(3)t(3;7;8). Suzukawa, K., Kodera, T., Shimizu, S., Nagasawa, T., Asou, H., Kamada, N., Taniwaki, M., Yokota, J., Morishita, K. Leukemia (1999) [Pubmed]
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