t(2;3)(p15-23;q26-27) ?/MECOM

2005-08-01   Jean-Loup Huret  

1.Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France
2.Clinical Cytogeneticist, UMC St. Radboud, Dept. Human Genetics, Div. Cytogenetics, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands

Clinics and Pathology

Disease

Myeloid malignancies: myelodysplastic syndrome (MDS) in 1/4 of cases, with various FAB diagnoses (refractory anaemia (RA), RA with ringed sideroblasts (RARS), RA with excess of blasts (RAEB), RAEB in transformation (RAEB-t), and chronic myelomonocytic leukemia (CMML)), acute myeloid leukaemia (AML) in 60% of cases (M2-AML in 1/4 of all cases), blast crisis of a chronic myelogenous leukaemia (BC-CML) in about 10% of cases

Etiology

1/4 of cases were therapy related leukemias, and 10% were BC-CML cases

Epidemiology

At least 50 cases described; sex ratio: 1.33 M/F; median age around 50 yrs, most patients being between 30 and 70 yr old (range 3-80 yrs).

Cytology

High platelet count, dysmegakaryopoiesis, and multilineage dysplasia in 80 to 90% of cases

Prognosis

Median survival 12 months (range 1-53 mths), with a few patients surviving with bone marrow transplantation.

Cytogenetics

Note

Heterogeneous breakpoints by cytogenetic and FISH analysis; FISH mapping of 2p breakpoints was very heterogeneous ranging from p14 or p15 to p23; FISH mapping of the 3q breakpoint was within the EVI1-MDS region (between RP11-694D5 (centromeric) and RP11-362K14 (telomeric) in the great majority of cases.

Additional anomalies

Sole anomaly in 40%, associated with -7 in 30%, with del(5q) in 15%, with del(7q) in 10%, with t(9;22)(q34;q11) in 10%, and with a complex karyotype in 20% of cases.

Genes Involved and Proteins

Note
Molecular analysis has been performed in only a very few cases. In most of these, ectopic expression of EVI1 was demonstrated, but rare cases seem not to involve this gene. Therefore, characteristics of EVI1 involvement (high platelet count, multilineage dysplasia, monosomy 7, prior history of carcinogen exposure and a poor prognosis) may not be present in further cases with apparently the same breakpoints.
The gene(s) involved in chromosome 2 is/are unknown
Gene name
MECOM (Ecotropic Viral Integration Site 1 (EVI1) and Myelodysplastic Syndrome 1 (MDS1-EVI1)
Location
3q26.2
Note
There is a direct correlation between mapping of the 3q breakpoint in the above given EVI1-MDS region and EVI1 ectopic expression by RT-PCR. Rare case with 3q break outside this interval failed to show ectopic expression of EVI1.
Dna rna description
EVI1 contains 12 exons.
Protein description
EVI1 may play an important role in organogenesis, cell migration, cell growth, and differentiation.

Highly cited references

Pubmed IDYearTitleCitations
298754172018SETBP1 induces transcription of a network of development genes by acting as an epigenetic hub.21
316483212019Transcriptome analysis offers a comprehensive illustration of the genetic background of pediatric acute myeloid leukemia.17
308860512019Identification of human silencers by correlating cross-tissue epigenetic profiles and gene expression.17
332396962020Genetic predisposition to hypertension is associated with preeclampsia in European and Central Asian women.16
295403402018MECOM-associated syndrome: a heterogeneous inherited bone marrow failure syndrome with amegakaryocytic thrombocytopenia.16
290471442018MECOM, HBS1L-MYB, THRB-RARB, JAK2, and TERT polymorphisms defining the genetic predisposition to myeloproliferative neoplasms: A study on 939 patients.16
304623092019Direct interaction between the PRDM3 and PRDM16 tumor suppressors and the NuRD chromatin remodeling complex.15
303477592018PR/SET Domain Family and Cancer: Novel Insights from the Cancer Genome Atlas.14
303358942019Microarray-based identification of genes associated with prognosis and drug resistance in ovarian cancer.13
320443792020The conserved and divergent roles of Prdm3 and Prdm16 in zebrafish and mouse craniofacial development.12
322194472020Atypical 3q26/MECOM rearrangements genocopy inv(3)/t(3;3) in acute myeloid leukemia.11
339035932021PAX8 and MECOM are interaction partners driving ovarian cancer.10
296769542018Genome-wide association study identifies loci and candidate genes for internal organ weights in Simmental beef cattle.10
331473382020Whole transcriptome sequencing detects a large number of novel fusion transcripts in patients with AML and MDS.9
314195112019A Multigene Model for Predicting Tumor Responsiveness After Preoperative Chemoradiotherapy for Rectal Cancer.9
311710002019High IL2RA mRNA expression is an independent adverse prognostic biomarker in core binding factor and intermediate-risk acute myeloid leukemia.9
333348992021Integrated genomic profiling and modelling for risk stratification in patients with advanced oesophagogastric adenocarcinoma.8
326061372020Leukemia Cell of Origin Influences Apoptotic Priming and Sensitivity to LSD1 Inhibition.8
305757562018Homeogene emx1 is required for nephron distal segment development in zebrafish.8
290974972018MDS1 and EVI1 complex locus (MECOM): a novel candidate gene for hereditary hematological malignancies.8
296230142018Genetic alterations and PIK3CA gene mutations and amplifications analysis in cervical cancer by racial groups in the United States.8
320726982020Matrine triggers colon cancer cell apoptosis and G0/G1 cell cycle arrest via mediation of microRNA-22.7
308926902019Multisite analysis of high-grade serous epithelial ovarian cancers identifies genomic regions of focal and recurrent copy number alteration in 3q26.2 and 8q24.3.7
337627422021MECOM permits pancreatic acinar cell dedifferentiation avoiding cell death under stress conditions.6
335799572021The acquisition of molecular drivers in pediatric therapy-related myeloid neoplasms.6
338117462021Tumor genomic, transcriptomic, and immune profiling characterizes differential response to first-line platinum chemotherapy in high grade serous ovarian cancer.6
331064752020Genome-wide association studies of antidepressant class response and treatment-resistant depression.6
323302452020EVI1 and GATA2 misexpression induced by inv(3)(q21q26) contribute to megakaryocyte-lineage skewing and leukemogenesis.6
322035062020The Caenorhabditis elegans homolog of the Evi1 proto-oncogene, egl-43, coordinates G1 cell cycle arrest with pro-invasive gene expression during anchor cell invasion.6
348180472021Predicting master transcription factors from pan-cancer expression data.5
296033692018Clinical and genetic risk factors for decreased bone mineral density in Japanese patients with inflammatory bowel disease.5
331068452021Genome-Wide Gene-by-Smoking Interaction Study of Chronic Obstructive Pulmonary Disease.4
329002602020All-trans retinoic acid in non-promyelocytic acute myeloid leukemia: driver lesion dependent effects on leukemic stem cells.4
305768682019t(3;8)(q26.2;q24) Often Leads to MECOM/MYC Rearrangement and Is Commonly Associated with Therapy-Related Myeloid Neoplasms and/or Disease Progression.4
307840602019Clinical and biological features of paediatric acute myeloid leukaemia (AML) with primary induction failure in the Japanese Paediatric Leukaemia/Lymphoma Study Group AML-05 study.4
292004072018A MECOM variant in an African American child with radioulnar synostosis and thrombocytopenia.4
354186852022Mapping human haematopoietic stem cells from haemogenic endothelium to birth.3
326999822019Efficacy of All-Trans-Retinoic Acid in High-Risk Acute Myeloid Leukemia with Overexpression of EVI1.3
318205612020Two effects of GATA2 enhancer repositioning by 3q chromosomal rearrangements.3
311095912019Deciphering the complexities of MECOM rearrangement-driven chromosomal aberrations.3
350441642022MeCOM: A Method for Comparing Three-Dimensional Metalloenzyme Active Sites.2
336436712021Concurrent Central Diabetes Insipidus and Acute Myeloid Leukemia.2
326769332020Analytical and Potential Clinical Performance of Oncomine Myeloid Research Assay for Myeloid Neoplasms.2
329983302020Evi1 Counteracts Anti-Leukemic and Stem Cell Inhibitory Effects of All-Trans Retinoic Acid on Flt3-ITD/Npm1c-Driven Acute Myeloid Leukemia Cells.2
317118892020Lenalidomide Plus Hypomethylating Agent as a Treatment Option in Acute Myeloid Leukemia With Recurrent Genetic Abnormalities-AML With inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2); GATA2, MECOM.2
354895542022High Diversity of Glycosphingolipid Glycans of Colorectal Cancer Cell Lines Reflects the Cellular Differentiation Phenotype.1
350081062022Genome-wide DNA methylation analysis in pediatric acute myeloid leukemia.1
347225202021Comprehensive Analysis of E3 Ubiquitin Ligases Reveals Ring Finger Protein 223 as a Novel Oncogene Activated by KLF4 in Pancreatic Cancer.1
347806482022MS4A3 promotes differentiation in chronic myeloid leukemia by enhancing common β-chain cytokine receptor endocytosis.1
3443601720213q26 Amplifications in Cervical Squamous Carcinomas.1
344045322021Congenital amegakaryocytic thrombocytopenia - Not a single disease.1
331102382021Myeloid neoplasms associated with t(3;12)(q26.2;p13) are clinically aggressive, show myelodysplasia, and frequently harbor chromosome 7 abnormalities.1
334320642021Identification of loci associated with susceptibility to bovine paratuberculosis and with the dysregulation of the MECOM, eEF1A2, and U1 spliceosomal RNA expression.1
321895452020Prognosis of MECOM (EVI1)-rearranged MDS and AML patients rather depends on accompanying molecular mutations than on blast count.1
325352472020MECOM rearrangement involving the MYC locus: Two additional patients with the rare translocation, t(3;8)(q26.2;q24), and molecular review.1
319026942020Secondary acquisition of BCR-ABL1 fusion in de novo GATA2-MECOM positive acute myeloid leukemia with subsequent emergence of a rare KMT2A-ASXL2 fusion.1
311618572019Hematopoietic transformation in the absence of MLL1/KMT2A: distinctions in target gene reactivation.1
315547432019MECOM: A Very Interesting Gene Involved also in Lymphoid Malignancies.1
293563892018Somatic MECOM mosaicism in a patient with congenital bone marrow failure without a radial abnormality.1
295722392018Identification of novel MECOM gene fusion and personalized therapeutic targets through integrative clinical sequencing in secondary acute myeloid leukemia in a patient with severe congenital neutropenia: a case report and literature review.1
295366892018[Transcription factors analysis of subchondral bone in early experimental osteoarthritis based on gene expression profiles].1
302080122018A t(3;8)(q26.2;q24) involving the EVI1 (MECOM) Gene.1
357093542022Aberrant EVI1 splicing contributes to EVI1-rearranged leukemia.0
356451462022Myeloid neoplasms with 8q24/MYC rearrangement are frequently associated with myelodysplasia, complex karyotype, TP53 alterations, and inferior survival.0
354702772022Clinical and Genomic Profiles of Korean Patients with MECOM Rearrangement and the t(3;21)(q26.2;q22.1) Translocation.0
357333382022CRISPR-mediated MECOM depletion retards tumor growth by reducing cancer stem cell properties in lung squamous cell carcinoma.0
355728392022Single-Cell Transcriptome Analysis Reveals the Importance of IRF1/FSTL1 in Synovial Fibroblast Subsets for the Development of Rheumatoid Arthritis.0
352195932022MECOM-related disorder: Radioulnar synostosis without hematological aberration due to unique variants.0
359495542022MECOM promotes supporting cell proliferation and differentiation in cochlea.0
354849802022A novel MECOM variant associated with congenital amegakaryocytic thrombocytopenia and radioulnar synostosis.0
350389582022MECOM gene overexpression in pediatric patients with acute myeloid leukemia.0
359990342022Performance evaluation and clinical impact of the Oncomine Myeloid Research Assay for gene expression analysis in myeloid haematologic malignancies.0
359151432022High-resolution structural variant profiling of myelodysplastic syndromes by optical genome mapping uncovers cryptic aberrations of prognostic and therapeutic significance.0
351740832022MECOM/PRDM3 and PRDM16 Serve as Prognostic-Related Biomarkers and Are Correlated With Immune Cell Infiltration in Lung Adenocarcinoma.0
356826272022Molecular Classification and Overcoming Therapy Resistance for Acute Myeloid Leukemia with Adverse Genetic Factors.0
355815462022Machine learning approach informs biology of cancer drug response.0
351504482022COL4A1/COL4A2 and inherited platelet disorder gene variants in fetuses showing intracranial hemorrhage.0
349742902022Newly designed breakapart FISH probe helps to identify cases with true MECOM rearrangement in myeloid malignancies.0
351071262022The EDA-deficient mouse has Zymbal's gland hypoplasia and acute otitis externa.0
349588952022EVI1 protein interaction dynamics: Targetable for therapeutic intervention?0
352127152022Mapping the developing human cardiac endothelium at single cell resolution identifies MECOM as a regulator of arteriovenous gene expression.0
351324382022PRDM paralogs antagonistically balance Wnt/β-catenin activity during craniofacial chondrocyte differentiation.0
346682652022Comparison of myeloid neoplasms with nonclassic 3q26.2/MECOM versus classic inv(3)/t(3;3) rearrangements reveals diverse clinicopathologic features, genetic profiles, and molecular mechanisms of MECOM activation.0
351629732022EVI1 Promotes the Proliferation and Invasive Properties of Human Head and Neck Squamous Cell Carcinoma Cells.0
350208292022Phenotypic heterogeneity in individuals with MECOM variants in 2 families.0
344096432021Sex-specific genetic factors affect the risk of early-onset periodontitis in Europeans.0
346973732021Author Correction: Identification of loci associated with susceptibility to bovine paratuberculosis and with the dysregulation of the MECOM, eEF1A2, and U1 spliceosomal RNA expression.0
339096292021Bioinformatic analysis linking genomic defects to chemosensitivity and mechanism of action.0
336478142021BCR-ABL1 positive AML or CML in blast crisis? A pediatric case report with inv(3) and t(9;22) in the initial clone.0
336767662021Diagnosis of rare subtypes of acute myeloid leukaemia and related neoplasms.0
335421652021Utility of platelet cross-matching in a case of neonatal alloimmune thrombocytopenia associated with a de novo MECOM variant.0
330788732021Rare and novel RUNX1 fusions in myeloid neoplasms: A single-institute experience.0
328310082020A new case of myelodysplastic syndrome associated with t(3;3)(q21;q26) and inv(11)(p15q22).0
320647142020New MECOM variant in a child with severe neonatal cytopenias spontaneously resolving.0
305368402019A novel mutation in the MECOM gene causing radioulnar synostosis with amegakaryocytic thrombocytopenia (RUSAT-2) in an infant.0
314183632019[Efficacy of Quercetin-sensitized Adriamycin for Treatment of Refractory Acute Leukemia].0
311939892019Data on MECOM rearrangement-driven chromosomal aberrations in myeloid malignancies.0
305035642019Molecular and pathologic characterization of AML with double Inv(3)(q21q26.2).0
296660052018Unexpected favorable outcome in a patient with high grade B-cell lymphoma with abnormalities of MYC, BCL6 and BCL2 loci.0
294391872018Lethal neonatal bone marrow failure syndrome with multiple congenital abnormalities, including limb defects, due to a constitutional deletion of 3' MECOM.0

Article Bibliography

Pubmed IDLast YearTitleAuthors
89319991996Cytogenetic analysis in patients with primary myelodysplastic syndromes in leukaemic transformation. A report on 94 cases. Groupe Français de Cytogénétique Hématologique (GFCH).
66900211984Preliminary data on the in vitro proliferation pattern and karyotypic characteristics in cells of patients with ANLL.Barbieri D et al
78895041995Translocation (2;3)(p22;q28) is associated with myeloid disorders.Berger R et al
40635251985Rearrangements of chromosome 3 involving bands 3q21 and 3q26 are associated with normal or elevated platelet counts in acute nonlymphocytic leukemia.Bitter MA et al
119603922002Structural rearrangements of chromosome 3 in 57 patients with acute myeloid leukemia: clinical, hematological and cytogenetic features.Charrin C et al
20139771991Molecular diagnosis of Philadelphia negative CML using the polymerase chain reaction and DNA analysis: clinical features and course of M-bcr negative and M-bcr positive CML.Dobrovic A et al
86252691996Translocation (2;3)(p13;q26) in two cases of myeloid malignancies. Acute myeloblastic leukemia (M2) and blastic phase of chronic myeloid leukemia.Fleischman EW et al
101986251999Translocation (2;3)(p21;q26) as the sole anomaly in a case of primary myelofibrosis.Herens C et al
86839921996Abberant cytogenetic evolution pattern of Philadelphia-positive chronic myeloid leukemia treated with interferon-alpha.Johansson B et al
15552001992t(2;3)(p13;q26) in a case of chronic myeloid leukemia. Importance of the involvement of 3q26.Kwong YL et al
86160641996t(2;3)(p23;q26) in a patient with AML M2.Levaltier X et al
119642742002Distinct clinical outcomes for cytogenetic abnormalities evolving from aplastic anemia.Maciejewski JP et al
657586019833q-, 3q+ anomaly in malignant proliferations in humans.Mecucci C et al
119795482002Spectral karyotyping in patients with acute myeloid leukemia and a complex karyotype shows hidden aberrations, including recurrent overrepresentation of 21q, 11q, and 22q.Mrózek K et al
107799952000Secondary leukemia in a child with neuroblastoma while on oral etoposide: what is the cause?Ng A et al
72725061981Nonrandom chromosome abnormalities in acute leukemia and dysmyelopoietic syndromes in patients with previously treated malignant disease.Rowley JD 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
38910741985The 5q-anomaly.Van den Berghe H et al
33379041988Cytogenetic studies in patients with secondary leukemia/dysmyelopoietic syndrome after different treatment modalities.Whang-Peng J et al
66923341984Recurrent chromosomal defects are found in most patients with acute nonlymphocytic leukemia.Yunis JJ et al
86523791996Cytogenetic clonality analysis: typical patterns in myelodysplastic syndrome and acute myeloid leukaemia.van Lom K et al

Summary

Note

There are 2 subtypes of the t(2p;3q); in one type the breakpoint on chromosome 2 is assigned to bands 2p21-23, whereas the breakpoint for the other type of breakpoint is localized at 2p15-21.
Atlas Image
Partial GTG (Marian Stevens-Kroef, left) and RFA (Anne Hagemeijer, right) banded karyotypes of t(2;3)( p15-23;q26-27) with the distal (A) and proximal (B) breakpoint on chromosome 2.

Citation

Jean-Loup Huret

t(2;3)(p15-23;q26-27) ?/MECOM

Atlas Genet Cytogenet Oncol Haematol. 2005-08-01

Online version: http://atlasgeneticsoncology.org/haematological/1274/deep-insight-explorer/js/lib/case-report-explorer/

Historical Card

2004-05-01 t(2;3)(p15-23;q26-27) ?/MECOM by  Marian Stevens-Kroef 

Clinical Cytogeneticist, UMC St. Radboud, Dept. Human Genetics, Div. Cytogenetics, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands