MECOM (Ecotropic Viral Integration Site 1 (EVI1) and Myelodysplastic Syndrome 1 (MDS1-EVI1)

2015-05-01   Rotraud Wieser 


Atlas Image
Genomic locus of the human EVI1 gene, and EVI1 and MDS1/EVI1 mRNA variants. Asterisk, translation initiation codon in EVI1 exon 3; diamond, translation stop codon in EVI1 exon 16. (This figure was reprinted from Gene 396, R. Wieser, The oncogene and developmental regulator EVI1: Expression, biochemical properties, and biological functions, pages 346-357, Copyright Elsevier (2007), with permission from Elsevier. Gene homepage:
Atlas Image
MECOM (Ecotropic Viral Integration Site 1 (EVI1) and Myelodysplastic Syndrome 1 (MDS1-EVI1) Hybridization with MECOM (EVI1) break apart probe (Kreatech, Leica Biosystems Inc., US) showing the gene on 3q26.2 (red-green or a fused yellow signal) - Courtesy Adriana Zamecnikova


The MECOM locus in chromosome band 3q26.2 gives rise to two major mRNA and protein species, EVI1 and MDS1\/EVI1, of which the former has been characterized far more extensively. EVI1 has been implicated in the maintenance and expansion of normal hematopoietic stem cells. In addition, it plays a role as an oncogene in myeloid leukemia and in certain solid tumors, its overexpression being associated with a dismal prognosis in several of these malignancies. EVI1 exerts its biological effects mainly by regulating gene transcription, and does so by acting as a sequence specific transcription factor, by modulating the activity of other sequence specific transcription factors, and by regulating promoter CpG island methylation.



The human EVI1 gene spans approximately 65 kb of genomic DNA. 14 of its 16 exons are coding (Fig. 1A). Transcription can initiate from alternative exons 1a, 1b, 1c, 1d, or 3L (Fig. 1B), and several alternative splice variants of the EVI1 mRNA have been described (Delta324, -Rp9, Delta105; Fig. 1A).
The human MDS1 gene consists of 4 exons spread over a genomic region of more than 500 kb. MDS1 exon 4 is located less than 2 kb upstream of EVI1 exon1a. MDS1 can also be expressed on its own. The MDS1/EVI1 mRNA presumably results from splicing of the second exon of MDS1 to the second exon of EVI1 (Fig. 1B).


Telomere to centromere.


Atlas Image
EVI1 and MDS1/EVI1 protein domains. Black boxes, zinc finger motifs; RD, repression domain; ac, acidic region; PR, PR domain. This figure was reprinted in modified form from Gene 396, R. Wieser, The oncogene and developmental regulator EVI1: Expression, biochemical properties, and biological functions, pages 346-357, Copyright Elsevier (2007), with permission from Elsevier. Gene homepage:


Exon 3 of the human EVI1 gene contains two closely spaced ATG codons, either of which may serve as the translation initiation site. Depending on which ATG is used, proteins of 1051 or 1041 amino acids will be formed. EVI1 contains two domains of seven and three zinc finger motifs, respectively, a repression domain between the two sets of zinc fingers, and an acidic domain at its C-terminus. It is a 145 kDa protein that is capable of binding to DNA in a sequence specific manner, and that interacts with transcriptional coactivators and corepressors as well as other sequence specific transcription factors. DNA binding and transcriptional regulation by EVI1 are influenced by posttranslational modifications like phosphorylation, acetylation, and sumoylation (Chakraborty et al, 2001; Shimahara et al, 2010; Bard-Chapeau et al, 2013; Singh et al, 2013; White et al, 2013).
Predicted translation of MDS1-EVI1 adds 188 amino acids to the N-terminus of EVI1. 63 of these additional amino acids are encoded by exon 2 and beginning of exon 3 of EVI1, and the remaining 125 from the MDS1 gene. MDS1-EVI1 contains a PR domain, which is about 40% homologous to the N-terminus of the retinoblastoma-binding protein, RIZ, and the PRDI-BF1 transcription factor. Some biological functions of MDS1/EVI1 were reported to be different from, or even antagonistic to, those of EVI1, while in other cases, EVI1 and MDS1/EVI1 acted in a similar manner. MDS1/EVI1 (PRDM3) has H3K9me1 methyltransferase activity and a role in maintaining heterochromatin integrity (Pinheiro et al, 2012).


Among human tissues/organs, the EVI1 mRNA is expressed abundantly in kidney, lung, pancreas, stomach, ovaries, uterus, and prostate, to a lesser extent in the small intestine, colon, thymus, spleen, heart, brain, testis, and placenta, and at very low levels in skeletal muscle and bone marrow. The pattern of expression of MDS1-EVI1 is very similar to that of EVI1.
In the adult mouse, the Evi1 mRNA is expressed, at varying levels, in the kidney, lung, stomach, ovary, uterus, intestine, thymus, spleen, heart, brain, and liver. In the mouse embryo, Evi1 mRNA levels are high in the urinary system and Mullerian ducts, the lung, the heart, and the emerging limb buds.
Similar Evi1 expression patterns were also observed in Xenopus, chicken, and zebrafish.
In human and murine hematopoiesis, EVI1 mRNA levels are high in the most immature cell populations and decline in the course of differentiation (Kataoka et al, 2011; Bindels et al, 2012; Steinleitner et al, 2012).
EVI1 expression is regulated by RUNX1 and ELK1, by retinoic acid via RAR/RXR, and by certain MLL fusion proteins (Bingemann et al, 2009; Arai et al, 2011; Maicas et al, 2013).


Nuclear; in part in speckles.


Because of the spatially and temporally restricted expression of MECOM, it has been suggested that this gene plays important roles in development and could be involved in organogenesis, cell migration, cell growth, and differentiation.
In the mouse, homozygous disruption of the 6th exon of the Evi1 gene led to embryonic lethality, with widespread hypocellularity, reduced body size, small or absent limb buds, a pale yolk sac and placenta, abnormal development of the nervous system and the heart, and massive haemorrhaging. (Hoyt et al, 1997). Functions of Evi1 and/or Mds1/Evi1 in heart development, spine formation, and, particularly, maintenance and expansion of hematopoietic stem cells (HSCs) have been deduced from, or confirmed through, the phenotypes of additional MECOM knockout models (Goyama et al, 2008; Kataoka et al, 2011; Zhang et al, 2011; Bard-Chapeau et al, 2014; Juneja et al, 2014). A role of Evi1 in HSCs was also corroborated through overexpression and gene marking experiments (Buonamici et al, 2004; Laricchia-Robbio et al, 2008; Dickstein et al, 2010; Kataoka et al, 2011).
Support for a role of Evi1 as a leukemia initiating and promoting oncogene has been obtained through mouse bone marrow transduction/transplantation models, in which overexpression of Evi1 alone caused a myelodysplastic syndrome (MDS) like disease, while its co-expression with other oncogenes led to AML (Buonamici et al, 2004; Jin et al, 2007; Watanabe-Okochi et al, 2008; Watanabe-Okochi et al, 2013). Even more compellingly, in a human gene therapy trial for chronic granulomatous disease, activating integrations of the therapeutic vector into the MECOM locus led to clonal expansion with progression to MDS and, ultimately, AML (Stein et al, 2010). Evi1 was proposed to be essential for AML leukemia stem cell (LSC) function since its experimental down-regulation reduced leukemogenicity in several mouse models of AML (Goyama et al, 2008; Bindels et al, 2012). Evi1 expression was also associated with leukemia initiating capacity in chronic myeloid leukemia (CML) (Sato et al, 2014). A prominent role of EVI1 in therapy resistance was suggested by a number of clinical trials, and illustrated by in vitro data demonstrating that its ectopic expression reduced, and its knockdown enhanced, cellular responsiveness to chemotherapeutic drugs (Bindels et al, 2012; Konantz et al, 2012; Yamakawa et al, 2012; Rommer et al, 2013).
Beyond its roles in normal and malignant hematopoiesis, EVI1 negatively regulated NF-kB dependent inflammation (Xu et al, 2012) and promoted adipocyte differentiation (Ishibashi et al, 2012).
EVI1 exerts its biological functions mainly by acting as a transcription factor. and regulates the expression of both protein coding and miRNA genes. Reported direct EVI1 target genes are MS4A3 (Heller et al, 2015), PLZF (Takahashi and Licht, 2002), Gata2 (Yuasa et al; 2005), Pbx1 (Shimabe et al, 2009), Pten (Yoshimi et al, 2011), Gpr56 (Saito et al, 2013), DeltaNp63 (Nayak et al, 2013), Bcl-xL (Pradhan et al, 2011), Calreticulin (Qiu et al, 2008), Ppargamma2 (Ishibashi et al, 2012), miR-1-2 (Gomez-Benito et al, 2010), miR-9 (Senyuk et al, 2013), miR-124 (Dickstein et al, 2010), and miR-449A (De Weer et al, 2011). ChIP-seq, combined with genome wide gene expression profiling, has been employed for large-scale identification of EVI1 target genes in ovarian cancer and murine myeloid cell lines (Bard-Chapeau et al, 2012; Glass et al, 2013). EVI1 associates with a number of transcriptional cofactors like HDAC1 (Vinatzer et al, 2001), CtBP1 (Palmer et al, 2001), CtBP2 (Turner and Crossley, 1998), CBP, P/CAF (Chakraborty et al, 2001), the histone methyl transferases SUV39H1 and G9a (Spensberger et al, 2008a; Goyama et al, 2010), the ATP dependent helicases BRG1 and BRM (Chi et al, 2003), and the member of histone deacetylase complex, Mbd3b (Spensberger et al, 2008b). EVI1 was also shown to interact with DNA methyl transferases (Lugthart et al, 2011; Senyuk et al, 2011), leading to methylation of CpG islands of some of its target genes, among them, CADM1 (Fisser et al, 2014), miR-9 (Senyuk et al, 2013), and miR-124 (Dickstein et al, 2010). Furthermore, EVI1 interacted with, and modulated the function of, other sequence specific transcription factors, e.g. GATA1 (Laricchia-Robbio et al, 2006), RUNX1/AML1 (Senyuk et al, 2007), PU.1 (Laricchia-Robbio et al, 2009), SMAD3 (Kurokawa et al, 1998; Izutsu et al, 2001; Alliston et al, 2005), FOS (Bard-Chapeau et al, 2012), NFkB (Xu et al, 2012), and RAR/RXR (Bingemann et al, 2009; Steinmetz et al, 2014).
In addition to its activity as a regulator of transcription, EVI1 has been reported to inhibit c-jun N-terminal kinase (Kurokawa et al, 2000), and to stimulate PI3K/AKT signalling (Liu et al, 2006; Yoshimi et al, 2011).


EVI1 orthologs are present in many species. EVI1 proteins from other mammals share more than 90% amino acid sequence identity with the human protein, and Xenopus EVI1 is 77% identical to its human counterpart. MDS1-EVI1 shares an overall homology with the C. elegans Egl 43 protein that includes the PR domain at the N-terminus and the two zinc-finger domains. An MDS1/EVI1 ortholog, hamlet, is also present in Drosophila.

Implicated in

3q21q26 syndrome. Chromosomal rearrangements located either 5 or 3 of the EVI1 gene can activate its transcription in haematopoietic cells. t(3;3)(q21;q26) breakpoints are often located 5 of EVI1, and inv(3)(q21q26) breakpoints 3 of it. In either case, transcription of EVI1 is activated by the distal enhancer of the GATA2 gene that is located in 3q21 (Gröschel et al, 2014; Yamazaki et al, 2014).
Patients with EVI1 rearrangements have elevated platelet counts, marked hyperplasia with dysplasia of megakaryocytes, and a poor prognosis.
Rearrangements at 3q26 may occur as a sole anomaly, but are often associated with monosomy 7 or deletion of the long arm of chromosome 7, and, less frequently, deletion in chromosome 5.
Atlas Image
Normal and leukemia-associated EVI1 protein variants.
Inappropriate expression of EVI1 in haematopoietic cells alters differentiation into granulocytes, erythrocytes and megakaryocytes. EVI1 promotes the proliferation of certain cell types, but inhibits the growth of others. It interferes with growth inhibition by TGF-b and with apoptosis elicited by a variety of stimuli. In a murine bone marrow transduction/transplantation model, experimental expression of EVI1 caused a disease resembling human myelodysplastic syndrome (Buonamici et al, 2004), while its coexpression with Hoxa9 and Meis 1, a mutated RUNX1 gene, or LIP led to overt leukemia (Jin et al, 2007; Watanabe-Okochi et al, 2008; Watanabe-Okochi et al, 2013).
Entity name
CML during the blast crisis and MDS in transformation.
Fusion protein
Overexpression of a fusion protein between the amino terminus of ETV6, which does not contain any functional domains, and the entire MDS1/EVI1 protein is driven by the ETV6 promoter.
Entity name
Therapy-related MDS/AML and CML during the blast crisis.
Fusion protein
RUNX1/MDS1/EVI1 is a chimeric transcription factor that interferes with RUNX1 functions in a dominant negative manner, but shares some biological effects with EVI1.
Entity name
Various cancers with known fusion genes
Other translocations involving MECOM at 3q26 have been found:
t(2;3)(p16;q26) BCL11A/MECOM in acute myeloid leukemia
t(3;21)(q26;q21) NRIP1/MECOM in acute myeloid leukemia (Haferlach et al., 2012) t(3;3)(q21;q26) LINC01565/MECOM in acute myeloid leukemia (Pekarsky et al., 1997)
t(3;7)(q26;q21) MECOM/CDK6 in myeloid leukemias
t(3;7)(q26;q34) TRB/MECOM in acute myeloid leukemia (M0-AML) (Suzukawa et al., 1999)
t(3;15)(q26;p13) MECOM/FRMD5 in lung adenocarcinoma (Yoshihara et al., 2014)
Entity name
AML without 3q26 rearrangements.
EVI1 may also be overexpressed in AML, MDS, or CML in blast crisis in the absence of any cytogenetically detectable 3q26 rearrangements.
Poor (AML).
Entity name
Acute lymphoblastic leukemia
Overexpression of EVI1 reported in some cases (Konantz et al, 2013; Su et al, 2015)
Entity name
Chronic lymphoblastic leukemia
Low EVI1 expression levels are associated with shorter survival (Vasyutina et al, 2015).
Entity name
Fanconi anemia
Overexpression of EVI1 (Meyer et al, 2007; Meyer et al, 2011)
Entity name
Ovarian cancer
Overexpression of EVI1
Poor (Nanjundan et al, 2007)
Entity name
Estrogen receptor negative breast cancer
Overexpression of EVI1
Poor (Patel et al, 2010)
Entity name
Infratentorial ependymoma
Overexpression of EVI1
Poor (Koos et al, 2011)
Entity name
Pancreatic cancer
Overexpression of EVI1 (Tanaka et al, 2014)
Entity name
Colon cancer
Overexpression of EVI1 (Deng et al, 2013)


Atlas Image


Pubmed IDLast YearTitleAuthors
158491932005Repression of bone morphogenetic protein and activin-inducible transcription by Evi-1.Alliston T et al
170149702006Conservation and expression of a novel alternatively spliced Evi1 exon.Alzuherri H et al
211909932011Evi-1 is a transcriptional target of mixed-lineage leukemia oncoproteins in hematopoietic stem cells.Arai S et al
160143222005Regulation of the expression of the oncogene EVI1 through the use of alternative mRNA 5'-ends.Aytekin M et al
245867492014Mice carrying a hypomorphic Evi1 allele are embryonic viable but exhibit severe congenital heart defects.Bard-Chapeau EA et al
123933832003High EVI1 expression predicts poor survival in acute myeloid leukemia: a study of 319 de novo AML patients.Barjesteh van Waalwijk van Doorn-Khosrovani S et al
81081381994Induction of two alternatively spliced evi-1 proto-oncogene transcripts by cAMP in kidney cells.Bartholomew C et al
225533142012EVI1 is critical for the pathogenesis of a subset of MLL-AF9-rearranged AMLs.Bindels EM et al
198431762009Zinc finger transcription factor ecotropic viral integration site 1 is induced by all-trans retinoic acid (ATRA) and acts as a dual modulator of the ATRA response.Bingemann SC et al
173412662007An interphase fluorescence in situ hybridisation assay for the detection of 3q26.2/EVI1 rearrangements in myeloid malignancies.Bobadilla D et al
21136691990Alternative splicing of the Evi-1 zinc finger gene generates mRNAs which differ by the number of zinc finger motifs.Bordereaux D et al
153433902004EVI1 induces myelodysplastic syndrome in mice.Buonamici S et al
115681822001Interaction 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 et al
145556512003EVI1 promotes cell proliferation by interacting with BRG1 and blocking the repression of BRG1 on E2F1 activity.Chi Y et al
215690102011EVI1-mediated down regulation of MIR449A is essential for the survival of EVI1 positive leukaemic cells.De Weer A et al
221618602013Overexpression of Evi-1 oncoprotein represses TGF-β signaling in colorectal cancer.Deng X et al
204482012010Methylation and silencing of miRNA-124 by EVI1 and self-renewal exhaustion of hematopoietic stem cells in murine myelodysplastic syndrome.Dickstein J et al
161097732005Insertional mutagenesis identifies genes that promote the immortalization of primary bone marrow progenitor cells.Du Y et al
254919452015Induction of the proapoptotic tumor suppressor gene Cell Adhesion Molecule 1 by chemotherapeutic agents is repressed in therapy resistant acute myeloid leukemia.Fisser MC et al
208421222010EVI1 controls proliferation in acute myeloid leukaemia through modulation of miR-1-2.Gómez-Benito M et al
238262132013Global Identification of EVI1 Target Genes in Acute Myeloid Leukemia.Glass C et al
197767572010EVI-1 interacts with histone methyltransferases SUV39H1 and G9a for transcriptional repression and bone marrow immortalization.Goyama S et al
186822422008Evi-1 is a critical regulator for hematopoietic stem cells and transformed leukemic cells.Goyama S et al
247037112014A single oncogenic enhancer rearrangement causes concomitant EVI1 and GATA2 deregulation in leukemia.Gröschel S et al
181811782008Expression and prognostic significance of different mRNA 5'-end variants of the oncogene EVI1 in 266 patients with de novo AML: EVI1 and MDS1/EVI1 overexpression both predict short remission duration.Haas K et al
228878042012Three novel cytogenetically cryptic EVI1 rearrangements associated with increased EVI1 expression and poor prognosis identified in 27 acute myeloid leukemia cases.Haferlach C et al
258866162015EVI1 promotes tumor growth via transcriptional repression of MS4A3.Heller G et al
92563451997The Evi1 proto-oncogene is required at midgestation for neural, heart, and paraxial mesenchyme development.Hoyt PR et al
224739982012An Evi1-C/EBPβ complex controls peroxisome proliferator-activated receptor γ2 gene expression to initiate white fat cell differentiation.Ishibashi J et al
108671282000The EVI-1 gene--its role in pathogenesis of human leukemias.Jółkowska J et al
172278322007Trib1 and Evi1 cooperate with Hoxa and Meis1 in myeloid leukemogenesis.Jin G et al
243164202014Deletion of Mecom in mouse results in early-onset spinal deformity and osteopenia.Juneja SC et al
220844052011Evi1 is essential for hematopoietic stem cell self-renewal, and its expression marks hematopoietic cells with long-term multilineage repopulating activity.Kataoka K et al
161568602005The Evi1 proto-oncoprotein blocks endomitosis in megakaryocytes by inhibiting sustained cyclin-dependent kinase 2 catalytic activity.Kilbey A et al
228284452013EVI-1 modulates leukemogenic potential and apoptosis sensitivity in human acute lymphoblastic leukemia.Konantz M et al
196057002009Inducible expression of EVI1 in human myeloid cells causes phenotypes consistent with its role in myelodysplastic syndromes.Konrad TA et al
214938672011The transcription factor evi-1 is overexpressed, promotes proliferation, and is prognostically unfavorable in infratentorial ependymomas.Koos B et al
108562402000The evi-1 oncoprotein inhibits c-Jun N-terminal kinase and prevents stress-induced cell death.Kurokawa M et al
192088462009EVI1 Impairs myelopoiesis by deregulation of PU.1 function.Laricchia-Robbio L et al
86160641996t(2;3)(p23;q26) in a patient with AML M2.Levaltier X et al
164627662006Evi1 is a survival factor which conveys resistance to both TGFbeta- and taxol-mediated cell death via PI3K/AKT.Liu Y et al
208558662011Aberrant DNA hypermethylation signature in acute myeloid leukemia directed by EVI1.Lugthart S et al
226890582013Functional characterization of the promoter region of the human EVI1 gene in acute myeloid leukemia: RUNX1 and ELK1 directly regulate its transcription.Maicas M et al
159051322005Evi-1 expression in Xenopus.Mead PE et al
216367192011Fanconi anemia (FA)-associated 3q gains in leukemic transformation consistently target EVI1, but do not affect low TERC expression in FA.Meyer S et al
172431622007Amplification and translocation of 3q26 with overexpression of EVI1 in Fanconi anemia-derived childhood acute myeloid leukemia with biallelic FANCD1/BRCA2 disruption.Meyer S et al
83138951994Generation of the AML1-EVI-1 fusion gene in the t(3;21)(q26;q22) causes blastic crisis in chronic myelocytic leukemia.Mitani K et al
21156461990Unique expression of the human Evi-1 gene in an endometrial carcinoma cell line: sequence of cDNAs and structure of alternatively spliced transcripts.Morishita K et al
174094142007Amplification of MDS1/EVI1 and EVI1, located in the 3q26.2 amplicon, is associated with favorable patient prognosis in ovarian cancer.Nanjundan M et al
236652362013EVI1 targets ΔNp63 and upregulates the cyclin dependent kinase inhibitor p21 independent of p53 to delay cell cycle progression and cell proliferation in colon cancer cells.Nayak KB et al
94478151997The EVI1 gene in myeloid leukemia.Nucifora G et al
81710261994Consistent intergenic splicing and production of multiple transcripts between AML1 at 21q22 and unrelated genes at 3q26 in (3;21)(q26;q22) translocations.Nucifora G et al
165829162006Correction of X-linked chronic granulomatous disease by gene therapy, augmented by insertional activation of MDS1-EVI1, PRDM16 or SETBP1.Ott MG et al
113288172001Evi-1 transforming and repressor activities are mediated by CtBP co-repressor proteins.Palmer S et al
210575392011Control of EVI-1 oncogene expression in metastatic breast cancer cells through microRNA miR-22.Patel JB et al
90448251997Fusion of ETV6 to MDS1/EVI1 as a result of t(3;12)(q26;p13) in myeloproliferative disorders.Peeters P et al
93072711997Activation of a novel gene in 3q21 and identification of intergenic fusion transcripts with ecotropic viral insertion site I in leukemia.Pekarsky Y et al
18938711991Patterns of Evi-1 expression in embryonic and adult tissues suggest that Evi-1 plays an important regulatory role in mouse development.Perkins AS et al
229396222012Prdm3 and Prdm16 are H3K9me1 methyltransferases required for mammalian heterochromatin integrity.Pinheiro I et al
163421722006EVI1 is consistently expressed as principal transcript in common and rare recurrent 3q26 rearrangements.Poppe B et al
219804342011Acetylation of the proto-oncogene EVI1 abrogates Bcl-xL promoter binding and induces apoptosis.Pradhan AK et al
183038592008Regulation of the calreticulin gene by GATA6 and Evi-1 transcription factors.Qiu Y et al
86958161996Fluorescence in situ hybridization analysis of t(3; 12)(q26; p13): a recurring chromosomal abnormality involving the TEL gene (ETV6) in myelodysplastic syndromes.Raynaud SD et al
234575462013EVI1 inhibits apoptosis induced by antileukemic drugs via upregulation of CDKN1A/p21/WAF in human myeloid cells.Rommer A et al
80494401994Expression of EVI1 in myelodysplastic syndromes and other hematologic malignancies without 3q26 translocations.Russell M et al
234786652013Maintenance of the hematopoietic stem cell pool in bone marrow niches by EVI1-regulated GPR56.Saito Y et al
247479722014Evi1 defines leukemia-initiating capacity and tyrosine kinase inhibitor resistance in chronic myeloid leukemia.Sato T et al
216951702011The oncoprotein EVI1 and the DNA methyltransferase Dnmt3 co-operate in binding and de novo methylation of target DNA.Senyuk V et al
175751322007Repression of RUNX1 activity by EVI1: a new role of EVI1 in leukemogenesis.Senyuk V et al
235092962013Critical role of miR-9 in myelopoiesis and EVI1-induced leukemogenesis.Senyuk V et al
197677692009Pbx1 is a downstream target of Evi-1 in hematopoietic stem/progenitors and leukemic cells.Shimabe M et al
203637502010Acetylation of lysine 564 adjacent to the C-terminal binding protein-binding motif in EVI1 is crucial for transcriptional activation of GATA2.Shimahara A et al
237700462013SUMO1 negatively regulates the transcriptional activity of EVI1 and significantly increases its co-localization with EVI1 after treatment with arsenic trioxide.Singh S et al
186199622008A novel interaction between the proto-oncogene Evi1 and histone methyltransferases, SUV39H1 and G9a.Spensberger D et al
200984312010Genomic instability and myelodysplasia with monosomy 7 consequent to EVI1 activation after gene therapy for chronic granulomatous disease.Stein S et al
231552562012EVI1 and MDS1/EVI1 expression during primary human hematopoietic progenitor cell differentiation into various myeloid lineages.Steinleitner K et al
254864802014The oncogene EVI1 enhances transcriptional and biological responses of human myeloid cells to all-trans retinoic acid.Steinmetz B et al
150851642004Translocation t(2;3)(p15-23;q26-27) in myeloid malignancies: report of 21 new cases, clinical, cytogenetic and molecular genetic features.Stevens-Kroef M et al
248288672015Aberrant expression of ecotropic viral integration site-1 in acute myeloid leukemia and acute lymphoblastic leukemia.Su G et al
104829861999Activation 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 et al
122006912002The human promyelocytic leukemia zinc finger gene is regulated by the Evi-1 oncoprotein and a novel guanine-rich site binding protein.Takahashi S et al
237521862014EVI1 oncogene promotes KRAS pathway through suppression of microRNA-96 in pancreatic carcinogenesis.Tanaka M et al
97246491998Cloning and characterization of mCtBP2, a co-repressor that associates with basic Krüppel-like factor and other mammalian transcriptional regulators.Turner J et al
165740972006Evi1 is specifically expressed in the distal tubule and duct of the Xenopus pronephros and plays a role in its formation.Van Campenhout C et al
259365282015The regulatory interaction of EVI1 with the TCL1A oncogene impacts cell survival and clinical outcome in CLL.Vasyutina E et al
124617522003Quantitative comparison of the expression of EVI1 and its presumptive antagonist, MDS1/EVI1, in patients with myeloid leukemia.Vinatzer U et al
125552182003Acute myelogenous leukemia with the t(3;12)(q26;p13) translocation: case report and review of the literature.Voutsadakis IA et al
235470502013The shortest isoform of C/EBPβ, liver inhibitory protein (LIP), collaborates with Evi1 to induce AML in a mouse BMT model.Watanabe-Okochi N et al
237766812013Phosphorylation of the leukemic oncoprotein EVI1 on serine 196 modulates DNA binding, transcriptional repression and transforming ability.White DJ et al
175071832007The oncogene and developmental regulator EVI1: expression, biochemical properties, and biological functions.Wieser R et al
125518232003Interphase fluorescence in situ hybridization assay for the detection of rearrangements of the EVI-1 locus in chromosome band 3q26 in myeloid malignancies.Wieser R et al
225818592012EVI1 acts as an inducible negative-feedback regulator of NF-κB by inhibiting p65 acetylation.Xu X et al
222951052012The increased expression of integrin α6 (ITGA6) enhances drug resistance in EVI1(high) leukemia.Yamakawa N et al
247039062014A remote GATA2 hematopoietic enhancer drives leukemogenesis in inv(3)(q21;q26) by activating EVI1 expression.Yamazaki H et al
165324392006t(3;21)(q26;q22) in myeloid leukemia: an aggressive syndrome of blast transformation associated with hydroxyurea or antimetabolite therapy.Yin CC et al
255005442015The landscape and therapeutic relevance of cancer-associated transcript fusions.Yoshihara K et al
212893082011Evi1 represses PTEN expression and activates PI3K/AKT/mTOR via interactions with polycomb proteins.Yoshimi A et al
158891402005Oncogenic transcription factor Evi1 regulates hematopoietic stem cell proliferation through GATA-2 expression.Yuasa H et al
88130931996Expression of EVI1 and the Retinoblastoma genes in acute myelogenous leukemia with t(3;13)(q26;q13-14).Yufu Y et al
216660532011PR-domain-containing Mds1-Evi1 is critical for long-term hematopoietic stem cell function.Zhang Y et al

Other Information

Locus ID:

NCBI: 2122
MIM: 165215
HGNC: 3498
Ensembl: ENSG00000085276


dbSNP: 2122
ClinVar: 2122
TCGA: ENSG00000085276


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
MAPK signaling pathwayKEGGko04010
Chronic myeloid leukemiaKEGGko05220
MAPK signaling pathwayKEGGhsa04010
Pathways in cancerKEGGhsa05200
Chronic myeloid leukemiaKEGGhsa05220
Chromatin organizationREACTOMER-HSA-4839726
Chromatin modifying enzymesREACTOMER-HSA-3247509
PKMTs methylate histone lysinesREACTOMER-HSA-3214841

Protein levels (Protein atlas)

Not detected


Pubmed IDYearTitleCitations
165829162006Correction of X-linked chronic granulomatous disease by gene therapy, augmented by insertional activation of MDS1-EVI1, PRDM16 or SETBP1.404
200984312010Genomic instability and myelodysplasia with monosomy 7 consequent to EVI1 activation after gene therapy for chronic granulomatous disease.279
247037112014A single oncogenic enhancer rearrangement causes concomitant EVI1 and GATA2 deregulation in leukemia.173
205121452010A genome-wide association study of nasopharyngeal carcinoma identifies three new susceptibility loci.133
229396222012Prdm3 and Prdm16 are H3K9me1 methyltransferases required for mammalian heterochromatin integrity.102
182728132008High EVI1 levels predict adverse outcome in acute myeloid leukemia: prevalence of EVI1 overexpression and chromosome 3q26 abnormalities underestimated.73
123933832003High EVI1 expression predicts poor survival in acute myeloid leukemia: a study of 319 de novo AML patients.65
203796142010Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.62
203086562010High EVI1 expression predicts outcome in younger adult patients with acute myeloid leukemia and is associated with distinct cytogenetic abnormalities.61
247039062014A remote GATA2 hematopoietic enhancer drives leukemogenesis in inv(3)(q21;q26) by activating EVI1 expression.60


Rotraud Wieser

MECOM (Ecotropic Viral Integration Site 1 (EVI1) and Myelodysplastic Syndrome 1 (MDS1-EVI1)

Atlas Genet Cytogenet Oncol Haematol. 2015-05-01

Online version:

Historical Card

2007-12-01 MECOM (Ecotropic Viral Integration Site 1 (EVI1) and Myelodysplastic Syndrome 1 (MDS1-EVI1) by  Rotraud Wieser 

2003-05-01 MECOM (Ecotropic Viral Integration Site 1 (EVI1) and Myelodysplastic Syndrome 1 (MDS1-EVI1) by  Soumen Chakraborty,Silvia Buonamici,Vitalyi Senyuk,Giuseppina Nucifora 

Dept. of Pathology(Rm.3314), Molecular Biology, Research Building University Of Illinois At Chicago 900 South Ashland Avenue Chicago, IL-60607, USA