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
356826272022Molecular Classification and Overcoming Therapy Resistance for Acute Myeloid Leukemia with Adverse Genetic Factors.169
366489032022Advances in Understanding the Genetic Mechanisms of Zebrafish Renal Multiciliated Cell Development.141
329002602020All-trans retinoic acid in non-promyelocytic acute myeloid leukemia: driver lesion dependent effects on leukemic stem cells.119
378105502023EVI1-mediated Programming of Normal and Malignant Hematopoiesis.118
376767682023Determinants of motor neuron functional subtypes important for locomotor speed.105
370911892023Emerging bone marrow failure syndromes- new pieces to an unsolved puzzle.99
388346132024Orthogonal proteogenomic analysis identifies the druggable PA2G4-MYC axis in 3q26 AML.96
348180472021Predicting master transcription factors from pan-cancer expression data.90
398034922024CEBPA repression by MECOM blocks differentiation to drive aggressive leukemias.86
359495542022MECOM promotes supporting cell proliferation and differentiation in cochlea.81
391488242024Genetics of Cardiac Aging Implicate Organ-Specific Variation.81
368027032023Multiancestry Genome-Wide Association Study of Aortic Stenosis Identifies Multiple Novel Loci in the Million Veteran Program.77
392275822024Efficient generation of human NOTCH ligand-expressing haemogenic endothelial cells as infrastructure for in vitro haematopoiesis and lymphopoiesis.77
292222832017Hereditary thrombocytopenias: a growing list of disorders.75
352127152022Mapping the developing human cardiac endothelium at single-cell resolution identifies MECOM as a regulator of arteriovenous gene expression.71
332396962020Genetic predisposition to hypertension is associated with preeclampsia in European and Central Asian women.71
260242152015Recent advances in elucidating the genetic mechanisms of nephrogenesis using zebrafish.71
3667240720233q26.2/MECOM Rearrangements by Pericentric Inv(3): Diagnostic Challenges and Clinicopathologic Features.69
365225442023A genetic disorder reveals a hematopoietic stem cell regulatory network co-opted in leukemia.68
371858142023Epigenetic landscape reveals MECOM as an endothelial lineage regulator.67
383578222024Directed Differentiation of Human Induced Pluripotent Stem Cells to Heart Valve Cells.63
377052442023Myelodysplasia after clonal hematopoiesis with APOBEC3-mediated CYBB inactivation in retroviral gene therapy for X-CGD.61
337627422021MECOM permits pancreatic acinar cell dedifferentiation avoiding cell death under stress conditions.57
378452282023Sleeping Beauty transposon mutagenesis identified genes and pathways involved in inflammation-associated colon tumor development.56
354186852022Mapping human haematopoietic stem cells from haemogenic endothelium to birth.55
370996862023Mecom mutation related to radioulnar synostosis with amegakaryocytic thrombocytopenia reduces HSPCs in mice.54
387487922024Oncogene EVI1 drives acute myeloid leukemia via a targetable interaction with CTBP2.53
357333382022CRISPR-mediated MECOM depletion retards tumor growth by reducing cancer stem cell properties in lung squamous cell carcinoma.53
395040412025Distinct Genetic Risk Profile in Aortic Stenosis Compared With Coronary Artery Disease.52
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.52
394684622024MECOM and the PRDM gene family in uterine endometrial cancer: bioinformatics and experimental insights into pathogenesis and therapeutic potentials.52
367895452023Pathologic, cytogenetic, and molecular features of acute myeloid leukemia with megakaryocytic differentiation: A report from the Children's Oncology Group.51
393330952024The microprotein HDSP promotes gastric cancer progression through activating the MECOM-SPINK1-EGFR signaling axis.50
295403402018MECOM-associated syndrome: a heterogeneous inherited bone marrow failure syndrome with amegakaryocytic thrombocytopenia.50
388836032024Potential molecular and cellular mechanisms of the effects of cuproptosis-related genes in the cardiomyocytes of patients with diabetic heart failure: a bioinformatics analysis.50
339035932021PAX8 and MECOM are interaction partners driving ovarian cancer.49
357093542022Aberrant EVI1 splicing contributes to EVI1-rearranged leukemia.49
391035562024An activity-regulated transcriptional program directly drives synaptogenesis.44
3443601720213q26 Amplifications in Cervical Squamous Carcinomas.44
366094742023A distal super-enhancer activates oncogenic ETS2 via recruiting MECOM in inflammatory bowel disease and colorectal cancer.42
351740832022MECOM/PRDM3 and PRDM16 Serve as Prognostic-Related Biomarkers and Are Correlated With Immune Cell Infiltration in Lung Adenocarcinoma.42
394271862024MECOM Locus classical transcript isoforms affect tumor immune microenvironment and different targets in ovarian cancer.40
370905162023Rewiring of master transcription factor cistromes during high-grade serous ovarian cancer development.40
361686362022DDX56 transcriptionally activates MIST1 to facilitate tumorigenesis of HCC through PTEN-AKT signaling.39
374226882023A phase 1/2 study of azacitidine, venetoclax and pevonedistat in newly diagnosed secondary AML and in MDS or CMML after failure of hypomethylating agents.39
393834582024Hematologic Cancer after Gene Therapy for Cerebral Adrenoleukodystrophy.38
380972062024Genome-wide association study of preserved ratio impaired spirometry (PRISm).36
383301442024Genetic Analysis of Obstructive Sleep Apnea and Its Relationship with Severe COVID-19.35
387480892024Outcome of 3q26.2/MECOM rearrangements in chronic myeloid leukemia.33
395763942024Systematic pan-cancer analysis of the prognostic value of MECOM in human cancer.33
386623492024High throughput screening aids clinical decision-making in refractory acute myeloid leukaemia.33
370671772023Expanded phenotypic and hematologic abnormalities beyond bone marrow failure in MECOM-associated syndromes.32
383167462024Efficacy of novel agents against cellular models of familial platelet disorder with myeloid malignancy (FPD-MM).30
384056622024The ETV6-MECOM fusion protein promotes EMT-related properties by repressing the transactivation activity of E-cadherin promoter in K562 leukemia cells.29
243092092014Zebrafish nephrogenesis is regulated by interactions between retinoic acid, mecom, and Notch signaling.29
372307702023Perinatal-lethal nonimmune fetal hydrops attributed to MECOM-associated bone marrow failure.26
382456832024A novel missense mutation in the MECOM gene in a Chinese boy with radioulnar synostosis with amegakaryocytic thrombocytopenia.26
269359372016Persistent polyclonal binucleated B-cell lymphocytosis and MECOM gene amplification.24
386624752024Unraveling facets of MECOM-associated syndrome: somatic genetic rescue, clonal hematopoiesis, and phenotype expansion.23
350208292022Phenotypic heterogeneity in individuals with MECOM variants in 2 families.17
387519572024A rare presentation of BCR-ABL1 and RUNX1-MECOM rearrangement in a pediatric patient with acute myeloid leukemia.17
268344902016Expression of MECOM is associated with unfavorable prognosis in glioblastoma multiforme.16
365785972023A family case series of inherited thrombocytopenia.13
374078732023MECOM Deficiency: from Bone Marrow Failure to Impaired B-Cell Development.0
284093412017Zebrafish Pronephros Development.0
291468832018A landscape of germ line mutations in a cohort of inherited bone marrow failure patients.0
391874682024Modelling and drug targeting of a myeloid neoplasm with atypical 3q26/MECOM rearrangement using patient-specific iPSCs.0
350389582022MECOM gene overexpression in pediatric patients with acute myeloid leukemia.0
368617322023Validation of the prognostic significance of the 2022 European LeukemiaNet risk stratification system in intensive chemotherapy treated aged 18 to 65 years patients with de novo acute myeloid leukemia.0
398537402025Mechanisms of enhancer-driven oncogene activation.0
376100302023A novel mutation in MECOM affects MPL regulation in vitro and results in thrombocytopenia and bone marrow failure.0
380869462024Preclinical efficacy of targeting epigenetic mechanisms in AML with 3q26 lesions and EVI1 overexpression.0
350441642022MeCOM: A Method for Comparing Three-Dimensional Metalloenzyme Active Sites.0
311095912019Deciphering the complexities of MECOM rearrangement-driven chromosomal aberrations.0
384408902024MECOM: a bioinformatics and experimentally identified marker for the diagnosis and prognosis of lung adenocarcinoma.0
322194472020Atypical 3q26/MECOM rearrangements genocopy inv(3)/t(3;3) in acute myeloid leukemia.0
369511952023Identifying prognostic gene panels in acute myeloid leukemia.0
349588952022EVI1 protein interaction dynamics: Targetable for therapeutic intervention?0
360958442023EVI1 drives leukemogenesis through aberrant ERG activation.0
389629962024Acute myeloid leukemia (AML) with chromosome 3 inversion: biology, management, and clinical outcome.0
393169922024Germline genetic variants that predispose to myeloproliferative neoplasms and hereditary myeloproliferative phenotypes.0
344045322021Congenital amegakaryocytic thrombocytopenia - Not a single disease.0
315547432019MECOM: A Very Interesting Gene Involved also in Lymphoid Malignancies.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
352195932022MECOM-related disorder: Radioulnar synostosis without hematological aberration due to unique variants.0
389954752024CRISPR-Cas9-mediated deletion enhancer of MECOM play a tumor suppressor role in ovarian cancer.0
274385272016Molecular basis of inherited thrombocytopenias: an update.0
349742902022Newly designed breakapart FISH probe helps to identify cases with true MECOM rearrangement in myeloid malignancies.0
318205612020Two effects of GATA2 enhancer repositioning by 3q chromosomal rearrangements.0
363325682022Vade-MECOM: How to peel back the layers of hematopoiesis.0
223724632012BCR-ABL1 tyrosine kinase sustained MECOM expression in chronic myeloid leukaemia.0
375854912023Phase I Results of Bromodomain and Extra-Terminal Inhibitor PLX51107 in Combination with Azacitidine in Patients with Relapsed/Refractory Myeloid Malignancies.0
379966992024The urothelial gene regulatory network: understanding biology to improve bladder cancer management.0
396330682025HMX3 is a critical vulnerability in MECOM-negative KMT2A::MLLT3 acute myelomonocytic leukemia.0
296660082018H2AFY is a novel fusion partner of MECOM in acute myeloid leukemia.0
215690102011EVI1-mediated down regulation of MIR449A is essential for the survival of EVI1 positive leukaemic cells.0
268151342016Complex chromosomal rearrangements leading to MECOM overexpression are recurrent in myeloid malignancies with various 3q abnormalities.0
388110252024Evaluation of European LeukemiaNet 2022 risk classification in patients undergoing allogeneic haematopoietic stem cell transplantation for acute myeloid leukaemia: Identification of a very poor prognosis genetic group.0
276203442017Intratumoral Heterogeneity of Frameshift Mutations in MECOM Gene is Frequent in Colorectal Cancers with High Microsatellite Instability.0
305035642019Molecular and pathologic characterization of AML with double Inv(3)(q21q26.2).0

Article Bibliography

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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
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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/teaching-explorer/favicon/css/lib/bootstrap.min.css

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