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

Written2003-05Soumen 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
Updated2007-12Rotraud Wieser
Medizinische Universitaet Wien, Department fuer Medizinische Genetik, Waehringerstr. 10, A-1090 Wien, Austria
Updated2015-05Rotraud Wieser
Medizinische Universitaet Wien, Clinic of Medicine I, Waehringer Guertel 18-20, A-1090 Wien, Austria rotraud.wieser@meduniwien.ac.at

Abstract 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.

Keywords Transcription regulation, myeloid leukemia, therapy resistance, hematopoietic stem cells

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Identity

Alias_namesMDS1
EVI1
myelodysplasia syndrome 1
ecotropic viral integration site 1
Alias_symbol (synonym)MDS1-EVI1
PRDM3
Other alias
HGNC (Hugo) MECOM
LocusID (NCBI) 2122
Atlas_Id 19
Location 3q26.2  [Link to chromosome band 3q26]
Location_base_pair Starts at 168801287 and ends at 168864093 bp from pter ( according to hg19-Feb_2009)  [Mapping MECOM.png]
 
  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: http://www.sciencedirect.com/science/journal/03781119)
Fusion genes
(updated 2016)
BCL11A (2p16.1) / MECOM (3q26.2)CDK6 (7q21.2) / MECOM (3q26.2)ETV6 (12p13.2) / MECOM (3q26.2)
HMCES (3q21.3) / MECOM (3q26.2)HOXD1 (2q31.1) / MECOM (3q26.2)LINC01565 (3q21.3) / MECOM (3q26.2)
MECOM (3q26.2) / CDK6 (7q21.2)MECOM (3q26.2) / ETV6 (12p13.2)MECOM (3q26.2) / EYA3 (1p35.3)
MECOM (3q26.2) / FRMD5 (15q15.3)MECOM (3q26.2) / HOXD1 (2q31.1)MECOM (3q26.2) / LMAN2L (2q11.2)
MECOM (3q26.2) / MECOM (3q26.2)MECOM (3q26.2) / PRDM16 (1p36.32)MECOM (3q26.2) / PSMD2 (3q27.1)
MECOM (3q26.2) / RAB7A (3q21.3)MECOM (3q26.2) / RPL22 (1p36.31)MECOM (3q26.2) / RPN1 (3q21.3)
MECOM (3q26.2) / RUNX1 (21q22.12)MECOM (3q26.2) / SHISA5 (3p21.31)NRIP1 (21q11.2) / MECOM (3q26.2)
PRDM16 (1p36.32) / MECOM (3q26.2)PRKCI (3q26.2) / MECOM (3q26.2)PSMD2 (3q27.1) / MECOM (3q26.2)
RPL22 (1p36.31) / MECOM (3q26.2)RPN1 (3q21.3) / MECOM (3q26.2)RUNX1 (21q22.12) / MECOM (3q26.2)
SKIL (3q26.2) / MECOM (3q26.2)THADA (2p21) / MECOM (3q26.2)TRB () / MECOM (3q26.2)
UBR2 (6p21.1) / MECOM (3q26.2)ZNF266 (19p13.2) / MECOM (3q26.2)

DNA/RNA

Description 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).
Transcription Telomere to centromere.

Protein

 
  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: http://www.sciencedirect.com/science/journal/03781119.
Description 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).
Expression 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).
Localisation Nuclear; in part in speckles.
Function 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).
Homology 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

Note
  
Entity t(3;3)(q21;q26) or inv(3)(q21q26)
Note 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).
Disease Acute Myelogenous Leukemia (AML), Myelodysplastic Syndrome (MDS), and Chronic Myelogenous Leukemia (CML).
Prognosis Patients with EVI1 rearrangements have elevated platelet counts, marked hyperplasia with dysplasia of megakaryocytes, and a poor prognosis.
Cytogenetics 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.
 
Normal and leukemia-associated EVI1 protein variants.
Oncogenesis 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 t(3;12)(q26;p13)
Disease CML during the blast crisis and MDS in transformation.
Prognosis Poor.
Cytogenetics Complex.
Abnormal 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 t(3;21)(q26;q22)
Disease Therapy-related MDS/AML and CML during the blast crisis.
Prognosis Poor.
Cytogenetics Complex.
Abnormal Protein RUNX1 /MDS1/EVI1
Oncogenesis 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 Various cancers with known fusion genes
Cytogenetics Other translocations involving MECOM at 3q26 have been found:
t(2;3)(p21;q26) THADA/MECOM in acute myeloid leukemia
t(2;3)(p16;q26) BCL11A/MECOM in acute myeloid leukemia
t(2;3)(q11;q26) MECOM/LMAN2L in ovarian carcinoma (Yoshihara et al., 2014)
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;8)(q26;q24) PVT1/MECOM in acute myeloid leukemia and myelodysplastic syndrome
t(3;15)(q26;p13) MECOM/FRMD5 in lung adenocarcinoma (Yoshihara et al., 2014)
t(3;21)(q26;q21) NRIP1/MECOM in acute myeloid leukemia (Haferlach et al., 2012)
  
  
Entity AML without 3q26 rearrangements.
Disease EVI1 may also be overexpressed in AML, MDS, or CML in blast crisis in the absence of any cytogenetically detectable 3q26 rearrangements.
Prognosis Poor (AML).
  
  
Entity Acute lymphoblastic leukemia
Note Overexpression of EVI1 reported in some cases (Konantz et al, 2013; Su et al, 2015)
  
  
Entity Chronic lymphoblastic leukemia
Prognosis Low EVI1 expression levels are associated with shorter survival (Vasyutina et al, 2015).
  
  
Entity Fanconi anemia
Note Overexpression of EVI1 (Meyer et al, 2007; Meyer et al, 2011)
  
  
Entity Ovarian cancer
Note Overexpression of EVI1
Prognosis Poor (Nanjundan et al, 2007)
  
  
Entity Estrogen receptor negative breast cancer
Note Overexpression of EVI1
Prognosis Poor (Patel et al, 2010)
  
  
Entity Infratentorial ependymoma
Note Overexpression of EVI1
Prognosis Poor (Koos et al, 2011)
  
  
Entity Pancreatic cancer
Note Overexpression of EVI1 (Tanaka et al, 2014)
  
  
Entity Colon cancer
Note Overexpression of EVI1 (Deng et al, 2013)
  

Breakpoints

 

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The Evi1 proto-oncoprotein blocks endomitosis in megakaryocytes by inhibiting sustained cyclin-dependent kinase 2 catalytic activity
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Br J Haematol 2005 Sep;130(6):902-11
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EVI-1 modulates leukemogenic potential and apoptosis sensitivity in human acute lymphoblastic leukemia
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Inducible expression of EVI1 in human myeloid cells causes phenotypes consistent with its role in myelodysplastic syndromes
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J Leukoc Biol 2009 Oct;86(4):813-22
PMID 19605700
 
The transcription factor evi-1 is overexpressed, promotes proliferation, and is prognostically unfavorable in infratentorial ependymomas
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The evi-1 oncoprotein inhibits c-Jun N-terminal kinase and prevents stress-induced cell death
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PMID 10856240
 
EVI1 Impairs myelopoiesis by deregulation of PU
Laricchia-Robbio L, Premanand K, Rinaldi CR, Nucifora G
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Blood 1996 Jul 15;88(2):682-9
PMID 8695816
 
EVI1 inhibits apoptosis induced by antileukemic drugs via upregulation of CDKN1A/p21/WAF in human myeloid cells
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Maintenance of the hematopoietic stem cell pool in bone marrow niches by EVI1-regulated GPR56
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Evi1 defines leukemia-initiating capacity and tyrosine kinase inhibitor resistance in chronic myeloid leukemia
Sato T, Goyama S, Kataoka K, Nasu R, Tsuruta-Kishino T, Kagoya Y, Nukina A, Kumagai K, Kubota N, Nakagawa M, Arai S, Yoshimi A, Honda H, Kadowaki T, Kurokawa M
Oncogene 2014 Oct 16;33(42):5028-38
PMID 24747972
 
The oncoprotein EVI1 and the DNA methyltransferase Dnmt3 co-operate in binding and de novo methylation of target DNA
Senyuk V, Premanand K, Xu P, Qian Z, Nucifora G
PLoS One 2011;6(6):e20793
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Repression of RUNX1 activity by EVI1: a new role of EVI1 in leukemogenesis
Senyuk V, Sinha KK, Li D, Rinaldi CR, Yanamandra S, Nucifora G
Cancer Res 2007 Jun 15;67(12):5658-66
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Critical role of miR-9 in myelopoiesis and EVI1-induced leukemogenesis
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Proc Natl Acad Sci U S A 2013 Apr 2;110(14):5594-9
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Pbx1 is a downstream target of Evi-1 in hematopoietic stem/progenitors and leukemic cells
Shimabe M, Goyama S, Watanabe-Okochi N, Yoshimi A, Ichikawa M, Imai Y, Kurokawa M
Oncogene 2009 Dec 10;28(49):4364-74
PMID 19767769
 
Acetylation of lysine 564 adjacent to the C-terminal binding protein-binding motif in EVI1 is crucial for transcriptional activation of GATA2
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J Biol Chem 2010 May 28;285(22):16967-77
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SUMO1 negatively regulates the transcriptional activity of EVI1 and significantly increases its co-localization with EVI1 after treatment with arsenic trioxide
Singh S, Pradhan AK, Chakraborty S
Biochim Biophys Acta 2013 Oct;1833(10):2357-68
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A novel interaction between the proto-oncogene Evi1 and histone methyltransferases, SUV39H1 and G9a
Spensberger D, Delwel R
FEBS Lett 2008 Aug 6;582(18):2761-7
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Genomic instability and myelodysplasia with monosomy 7 consequent to EVI1 activation after gene therapy for chronic granulomatous disease
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Nat Med 2010 Feb;16(2):198-204
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EVI1 and MDS1/EVI1 expression during primary human hematopoietic progenitor cell differentiation into various myeloid lineages
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Anticancer Res 2012 Nov;32(11):4883-9
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The oncogene EVI1 enhances transcriptional and biological responses of human myeloid cells to all-trans retinoic acid
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Leukemia 2004 Jun;18(6):1108-14
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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)
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Leukemia 1999 Sep;13(9):1359-66
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The human promyelocytic leukemia zinc finger gene is regulated by the Evi-1 oncoprotein and a novel guanine-rich site binding protein
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Citation

This paper should be referenced as such :
Wieser R
MECOM (Ecotropic Viral Integration Site 1 (EVI1) and Myelodysplastic Syndrome 1 (MDS1-EVI1);
Atlas Genet Cytogenet Oncol Haematol. in press
On line version : http://AtlasGeneticsOncology.org/Genes/EVI103q26ID19.html
History of this paper:
Chakraborty, S ; Buonamici, S ; Senyuk, V ; Nucifora, G. EVI1-MDS1/EVI1 (ecotropic viral integration site 1 (EVI1), myelodysplastic syndrome 1 (MDS1)-EVI1). Atlas Genet Cytogenet Oncol Haematol. 2003;7(3):160-161.
http://documents.irevues.inist.fr/bitstream/handle/2042/37976/05-2003-EVI103q26ID19.pdf
Wieser, R. EVI1 (ecotropic viral integration site 1 (EVI1), myelodysplastic syndrome 1 (MDS1)-EVI1). Atlas Genet Cytogenet Oncol Haematol. 2008;12(4):306-310.
http://documents.irevues.inist.fr/bitstream/handle/2042/38551/12-2007-EVI103q26ID19.pdf


Other Leukemias implicated (Data extracted from papers in the Atlas) [ 32 ]
  21q22 rearrangements (RUNX1) in treatment related leukemia
3q21q26 rearrangements (RPN1/MECOM) in treatment related leukemia
3q26 rearrangements (MECOM) in myeloid malignancies
Acute myeloid leukemia with myelodysplasia related changes
Classification of myelodysplastic syndromes 2015
Classification of myelodysplasic syndromes 1999
Chronic myelogenous leukaemia (CML)
inv(3)(q21q26) RPN1/MECOM::t(3;3)(q21;q26) RPN1/MECOM::ins(3;3)(q26;q21q26) RPN1/MECOM
inv(3)(p12q26) ?/MECOM
inv(3)(p24q26) ?/MECOM
inv(3)(q21q26) RPN1/MECOM
inv(3)(q23q26) ?/MECOM
t(1;3)(p36;q21) PSMD2/PRDM16 ???
t(2;3)(p16;q26) BCL11A/MECOM
t(2;3)(p21;q26) THADA/MECOM
t(2;3)(p15-23;q26-27) ?/MECOM
t(3;3)(p24;q26) ?/MECOM
t(3;5)(q26;q34) ?/MECOM
t(3;6)(q25;q26) ?/MECOM
t(3;7)(q26;q21) MECOM/CDK6
t(3;7)(q26;q21) CDK6/MECOM
t(3;8)(q26;q24) PVT1/MECOM
t(3;9)(q26;p23) ?/MECOM
t(3;11)(q26;p15) ?/MECOM
t(3;12)(q26;p13) ETV6/MECOM::t(3;12)(q26;p13) ETV6/EVI1
t(3;12)(q26;q21) ?/MECOM
t(3;17)(q26;q22) ?/MECOM
t(3;18)(q26;q11) ?/MECOM
t(3;21)(q26;q22) RUNX1/MECOM
t(3;21)(q26;q11) NRIP1/MECOM
t(3;21)(q26;q22) RUNX1/MECOM in treatment related leukemia
t(9;13)(p12;q21) PAX5/DACH1


External links

Nomenclature
HGNC (Hugo)MECOM   3498
Cards
AtlasEVI103q26ID19
Entrez_Gene (NCBI)MECOM  2122  MDS1 and EVI1 complex locus
AliasesAML1-EVI-1; EVI1; MDS1; MDS1-EVI1; 
PRDM3; RUSAT2
GeneCards (Weizmann)MECOM
Ensembl hg19 (Hinxton)ENSG00000085276 [Gene_View]  chr3:168801287-168864093 [Contig_View]  MECOM [Vega]
Ensembl hg38 (Hinxton)ENSG00000085276 [Gene_View]  chr3:168801287-168864093 [Contig_View]  MECOM [Vega]
ICGC DataPortalENSG00000085276
TCGA cBioPortalMECOM
AceView (NCBI)MECOM
Genatlas (Paris)MECOM
WikiGenes2122
SOURCE (Princeton)MECOM
Genetics Home Reference (NIH)MECOM
Genomic and cartography
GoldenPath hg19 (UCSC)MECOM  -     chr3:168801287-168864093 -  3q26.2   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)MECOM  -     3q26.2   [Description]    (hg38-Dec_2013)
EnsemblMECOM - 3q26.2 [CytoView hg19]  MECOM - 3q26.2 [CytoView hg38]
Mapping of homologs : NCBIMECOM [Mapview hg19]  MECOM [Mapview hg38]
OMIM165215   
Gene and transcription
Genbank (Entrez)AA043944 AF164154 AF164155 AF164156 AF164157
RefSeq transcript (Entrez)NM_001105077 NM_001105078 NM_001163999 NM_001164000 NM_001205194 NM_004991 NM_005241
RefSeq genomic (Entrez)NC_000003 NC_018914 NG_028279 NT_005612 NW_004929311
Consensus coding sequences : CCDS (NCBI)MECOM
Cluster EST : UnigeneHs.744090 [ NCBI ]
CGAP (NCI)Hs.744090
Alternative Splicing GalleryENSG00000085276
Gene ExpressionMECOM [ NCBI-GEO ]   MECOM [ EBI - ARRAY_EXPRESS ]   MECOM [ SEEK ]   MECOM [ MEM ]
Gene Expression Viewer (FireBrowse)MECOM [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)2122
GTEX Portal (Tissue expression)MECOM
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ13465   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ13465  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ13465
Splice isoforms : SwissVarQ13465
PhosPhoSitePlusQ13465
Domains : Interpro (EBI)MDS1   
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Conserved Domain (NCBI)MECOM
DMDM Disease mutations2122
Blocks (Seattle)MECOM
SuperfamilyQ13465
Human Protein AtlasENSG00000085276
Peptide AtlasQ13465
HPRD01310
IPIIPI00446866   IPI00943944   IPI00790776   IPI00921346   IPI00007525   IPI01022925   IPI00943898   IPI00976901   IPI00945324   IPI00978081   IPI00945685   IPI00796154   IPI00946142   IPI00946753   IPI00794507   
Protein Interaction databases
DIP (DOE-UCLA)Q13465
IntAct (EBI)Q13465
FunCoupENSG00000085276
BioGRIDMECOM
STRING (EMBL)MECOM
ZODIACMECOM
Ontologies - Pathways
QuickGOQ13465
Ontology : AmiGOhistone deacetylase complex  DNA binding  transcription factor activity, sequence-specific DNA binding  transcription factor activity, sequence-specific DNA binding  protein binding  nucleus  nucleoplasm  cytoplasm  Golgi apparatus  cytosol  transcription, DNA-templated  regulation of transcription, DNA-templated  apoptotic process  aggresome  nuclear speck  histone-lysine N-methyltransferase activity  cell differentiation  negative regulation of transforming growth factor beta receptor signaling pathway  histone lysine methylation  protein homodimerization activity  protein homodimerization activity  negative regulation of programmed cell death  intracellular membrane-bounded organelle  negative regulation of transcription, DNA-templated  positive regulation of transcription, DNA-templated  negative regulation of JNK cascade  metal ion binding  regulation of cell cycle  hematopoietic stem cell proliferation  
Ontology : EGO-EBIhistone deacetylase complex  DNA binding  transcription factor activity, sequence-specific DNA binding  transcription factor activity, sequence-specific DNA binding  protein binding  nucleus  nucleoplasm  cytoplasm  Golgi apparatus  cytosol  transcription, DNA-templated  regulation of transcription, DNA-templated  apoptotic process  aggresome  nuclear speck  histone-lysine N-methyltransferase activity  cell differentiation  negative regulation of transforming growth factor beta receptor signaling pathway  histone lysine methylation  protein homodimerization activity  protein homodimerization activity  negative regulation of programmed cell death  intracellular membrane-bounded organelle  negative regulation of transcription, DNA-templated  positive regulation of transcription, DNA-templated  negative regulation of JNK cascade  metal ion binding  regulation of cell cycle  hematopoietic stem cell proliferation  
Pathways : KEGGMAPK signaling pathway    Pathways in cancer    Chronic myeloid leukemia   
REACTOMEQ13465 [protein]
REACTOME Pathways3214841 [pathway]   
NDEx NetworkMECOM
Atlas of Cancer Signalling NetworkMECOM
Wikipedia pathwaysMECOM
Orthology - Evolution
OrthoDB2122
GeneTree (enSembl)ENSG00000085276
Phylogenetic Trees/Animal Genes : TreeFamMECOM
HOVERGENQ13465
HOGENOMQ13465
Homologs : HomoloGeneMECOM
Homology/Alignments : Family Browser (UCSC)MECOM
Gene fusions - Rearrangements
Fusion : MitelmanETV6/MECOM [12p13.2/3q26.2]  [t(3;12)(q26;p13)]  
Fusion : MitelmanLINC01565/MECOM [3q21.3/3q26.2]  [t(3;3)(q21;q26)]  
Fusion : MitelmanMECOM/CDK6 [3q26.2/7q21.2]  [t(3;7)(q26;q21)]  
Fusion : MitelmanMECOM/FRMD5 [3q26.2/15q15.3]  [t(3;15)(q26;q15)]  
Fusion : MitelmanMECOM/LMAN2L [3q26.2/2q11.2]  [t(2;3)(q11;q26)]  
Fusion : MitelmanMECOM/RPN1 [3q26.2/3q21.3]  [t(3;3)(q21;q26)]  
Fusion : MitelmanNRIP1/MECOM [21q11.2/3q26.2]  [t(3;21)(q26;q21)]  
Fusion : MitelmanRPN1/MECOM [3q21.3/3q26.2]  [inv(3)(q21q26)]  [t(3;3)(q21;q26)]  
Fusion : MitelmanRUNX1/MECOM [21q22.12/3q26.2]  [t(3;21)(q26;q22)]  
Fusion : MitelmanTRB/MECOM [-/3q26.2]  [ins(3;7)(q26;q34q22)]  
Fusion: TCGAMECOM 3q26.2 FRMD5 15q15.3 LUAD
Fusion: TCGAMECOM 3q26.2 LMAN2L 2q11.2 OV
Fusion: TCGAMECOM 3q26.2 RPN1 3q21.3 LAML
Fusion: TCGARUNX1 21q22.12 MECOM 3q26.2 LAML
Fusion : TICdbETV6 [12p13.2]  -  MECOM [3q26.2]
Fusion : TICdbRPN1 [3q21.3]  -  MECOM [3q26.2]
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerMECOM [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)MECOM
dbVarMECOM
ClinVarMECOM
1000_GenomesMECOM 
Exome Variant ServerMECOM
ExAC (Exome Aggregation Consortium)MECOM (select the gene name)
Genetic variants : HAPMAP2122
Genomic Variants (DGV)MECOM [DGVbeta]
DECIPHER (Syndromes)3:168801287-168864093  ENSG00000085276
CONAN: Copy Number AnalysisMECOM 
Mutations
ICGC Data PortalMECOM 
TCGA Data PortalMECOM 
Broad Tumor PortalMECOM
OASIS PortalMECOM [ Somatic mutations - Copy number]
Cancer Gene: CensusMECOM 
Somatic Mutations in Cancer : COSMICMECOM  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDMECOM
intOGen PortalMECOM
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch MECOM
DgiDB (Drug Gene Interaction Database)MECOM
DoCM (Curated mutations)MECOM (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)MECOM (select a term)
intoGenMECOM
NCG5 (London)MECOM
Cancer3DMECOM(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM165215   
Orphanet22871    11011    10703   
MedgenMECOM
Genetic Testing Registry MECOM
NextProtQ13465 [Medical]
TSGene2122
GENETestsMECOM
Huge Navigator MECOM [HugePedia]
snp3D : Map Gene to Disease2122
BioCentury BCIQMECOM
ClinGenMECOM
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD2122
Chemical/Pharm GKB GenePA27912
Clinical trialMECOM
Miscellaneous
canSAR (ICR)MECOM (select the gene name)
Probes
Litterature
PubMed133 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineMECOM
EVEXMECOM
GoPubMedMECOM
iHOPMECOM
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Wed Apr 12 11:31:32 CEST 2017

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