t(2;3)(p15-23;q26-27) ?/MECOM
2005-08-01 Jean-Loup Huret Affiliation1.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
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 ID | Year | Title | Citations |
|---|---|---|---|
| 35682627 | 2022 | Molecular Classification and Overcoming Therapy Resistance for Acute Myeloid Leukemia with Adverse Genetic Factors. | 169 |
| 36648903 | 2022 | Advances in Understanding the Genetic Mechanisms of Zebrafish Renal Multiciliated Cell Development. | 141 |
| 32900260 | 2020 | All-trans retinoic acid in non-promyelocytic acute myeloid leukemia: driver lesion dependent effects on leukemic stem cells. | 119 |
| 37810550 | 2023 | EVI1-mediated Programming of Normal and Malignant Hematopoiesis. | 118 |
| 37676768 | 2023 | Determinants of motor neuron functional subtypes important for locomotor speed. | 105 |
| 37091189 | 2023 | Emerging bone marrow failure syndromes- new pieces to an unsolved puzzle. | 99 |
| 38834613 | 2024 | Orthogonal proteogenomic analysis identifies the druggable PA2G4-MYC axis in 3q26 AML. | 96 |
| 34818047 | 2021 | Predicting master transcription factors from pan-cancer expression data. | 90 |
| 39803492 | 2024 | CEBPA repression by MECOM blocks differentiation to drive aggressive leukemias. | 86 |
| 35949554 | 2022 | MECOM promotes supporting cell proliferation and differentiation in cochlea. | 81 |
| 39148824 | 2024 | Genetics of Cardiac Aging Implicate Organ-Specific Variation. | 81 |
| 36802703 | 2023 | Multiancestry Genome-Wide Association Study of Aortic Stenosis Identifies Multiple Novel Loci in the Million Veteran Program. | 77 |
| 39227582 | 2024 | Efficient generation of human NOTCH ligand-expressing haemogenic endothelial cells as infrastructure for in vitro haematopoiesis and lymphopoiesis. | 77 |
| 29222283 | 2017 | Hereditary thrombocytopenias: a growing list of disorders. | 75 |
| 35212715 | 2022 | Mapping the developing human cardiac endothelium at single-cell resolution identifies MECOM as a regulator of arteriovenous gene expression. | 71 |
| 33239696 | 2020 | Genetic predisposition to hypertension is associated with preeclampsia in European and Central Asian women. | 71 |
| 26024215 | 2015 | Recent advances in elucidating the genetic mechanisms of nephrogenesis using zebrafish. | 71 |
| 36672407 | 2023 | 3q26.2/MECOM Rearrangements by Pericentric Inv(3): Diagnostic Challenges and Clinicopathologic Features. | 69 |
| 36522544 | 2023 | A genetic disorder reveals a hematopoietic stem cell regulatory network co-opted in leukemia. | 68 |
| 37185814 | 2023 | Epigenetic landscape reveals MECOM as an endothelial lineage regulator. | 67 |
| 38357822 | 2024 | Directed Differentiation of Human Induced Pluripotent Stem Cells to Heart Valve Cells. | 63 |
| 37705244 | 2023 | Myelodysplasia after clonal hematopoiesis with APOBEC3-mediated CYBB inactivation in retroviral gene therapy for X-CGD. | 61 |
| 33762742 | 2021 | MECOM permits pancreatic acinar cell dedifferentiation avoiding cell death under stress conditions. | 57 |
| 37845228 | 2023 | Sleeping Beauty transposon mutagenesis identified genes and pathways involved in inflammation-associated colon tumor development. | 56 |
| 35418685 | 2022 | Mapping human haematopoietic stem cells from haemogenic endothelium to birth. | 55 |
| 37099686 | 2023 | Mecom mutation related to radioulnar synostosis with amegakaryocytic thrombocytopenia reduces HSPCs in mice. | 54 |
| 38748792 | 2024 | Oncogene EVI1 drives acute myeloid leukemia via a targetable interaction with CTBP2. | 53 |
| 35733338 | 2022 | CRISPR-mediated MECOM depletion retards tumor growth by reducing cancer stem cell properties in lung squamous cell carcinoma. | 53 |
| 39504041 | 2025 | Distinct Genetic Risk Profile in Aortic Stenosis Compared With Coronary Artery Disease. | 52 |
| 29572239 | 2018 | Identification 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 |
| 39468462 | 2024 | MECOM and the PRDM gene family in uterine endometrial cancer: bioinformatics and experimental insights into pathogenesis and therapeutic potentials. | 52 |
| 36789545 | 2023 | Pathologic, cytogenetic, and molecular features of acute myeloid leukemia with megakaryocytic differentiation: A report from the Children's Oncology Group. | 51 |
| 39333095 | 2024 | The microprotein HDSP promotes gastric cancer progression through activating the MECOM-SPINK1-EGFR signaling axis. | 50 |
| 29540340 | 2018 | MECOM-associated syndrome: a heterogeneous inherited bone marrow failure syndrome with amegakaryocytic thrombocytopenia. | 50 |
| 38883603 | 2024 | Potential molecular and cellular mechanisms of the effects of cuproptosis-related genes in the cardiomyocytes of patients with diabetic heart failure: a bioinformatics analysis. | 50 |
| 33903593 | 2021 | PAX8 and MECOM are interaction partners driving ovarian cancer. | 49 |
| 35709354 | 2022 | Aberrant EVI1 splicing contributes to EVI1-rearranged leukemia. | 49 |
| 39103556 | 2024 | An activity-regulated transcriptional program directly drives synaptogenesis. | 44 |
| 34436017 | 2021 | 3q26 Amplifications in Cervical Squamous Carcinomas. | 44 |
| 36609474 | 2023 | A distal super-enhancer activates oncogenic ETS2 via recruiting MECOM in inflammatory bowel disease and colorectal cancer. | 42 |
| 35174083 | 2022 | MECOM/PRDM3 and PRDM16 Serve as Prognostic-Related Biomarkers and Are Correlated With Immune Cell Infiltration in Lung Adenocarcinoma. | 42 |
| 39427186 | 2024 | MECOM Locus classical transcript isoforms affect tumor immune microenvironment and different targets in ovarian cancer. | 40 |
| 37090516 | 2023 | Rewiring of master transcription factor cistromes during high-grade serous ovarian cancer development. | 40 |
| 36168636 | 2022 | DDX56 transcriptionally activates MIST1 to facilitate tumorigenesis of HCC through PTEN-AKT signaling. | 39 |
| 37422688 | 2023 | A 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 |
| 39383458 | 2024 | Hematologic Cancer after Gene Therapy for Cerebral Adrenoleukodystrophy. | 38 |
| 38097206 | 2024 | Genome-wide association study of preserved ratio impaired spirometry (PRISm). | 36 |
| 38330144 | 2024 | Genetic Analysis of Obstructive Sleep Apnea and Its Relationship with Severe COVID-19. | 35 |
| 38748089 | 2024 | Outcome of 3q26.2/MECOM rearrangements in chronic myeloid leukemia. | 33 |
| 39576394 | 2024 | Systematic pan-cancer analysis of the prognostic value of MECOM in human cancer. | 33 |
| 38662349 | 2024 | High throughput screening aids clinical decision-making in refractory acute myeloid leukaemia. | 33 |
| 37067177 | 2023 | Expanded phenotypic and hematologic abnormalities beyond bone marrow failure in MECOM-associated syndromes. | 32 |
| 38316746 | 2024 | Efficacy of novel agents against cellular models of familial platelet disorder with myeloid malignancy (FPD-MM). | 30 |
| 38405662 | 2024 | The ETV6-MECOM fusion protein promotes EMT-related properties by repressing the transactivation activity of E-cadherin promoter in K562 leukemia cells. | 29 |
| 24309209 | 2014 | Zebrafish nephrogenesis is regulated by interactions between retinoic acid, mecom, and Notch signaling. | 29 |
| 37230770 | 2023 | Perinatal-lethal nonimmune fetal hydrops attributed to MECOM-associated bone marrow failure. | 26 |
| 38245683 | 2024 | A novel missense mutation in the MECOM gene in a Chinese boy with radioulnar synostosis with amegakaryocytic thrombocytopenia. | 26 |
| 26935937 | 2016 | Persistent polyclonal binucleated B-cell lymphocytosis and MECOM gene amplification. | 24 |
| 38662475 | 2024 | Unraveling facets of MECOM-associated syndrome: somatic genetic rescue, clonal hematopoiesis, and phenotype expansion. | 23 |
| 35020829 | 2022 | Phenotypic heterogeneity in individuals with MECOM variants in 2 families. | 17 |
| 38751957 | 2024 | A rare presentation of BCR-ABL1 and RUNX1-MECOM rearrangement in a pediatric patient with acute myeloid leukemia. | 17 |
| 26834490 | 2016 | Expression of MECOM is associated with unfavorable prognosis in glioblastoma multiforme. | 16 |
| 36578597 | 2023 | A family case series of inherited thrombocytopenia. | 13 |
| 37407873 | 2023 | MECOM Deficiency: from Bone Marrow Failure to Impaired B-Cell Development. | 0 |
| 28409341 | 2017 | Zebrafish Pronephros Development. | 0 |
| 29146883 | 2018 | A landscape of germ line mutations in a cohort of inherited bone marrow failure patients. | 0 |
| 39187468 | 2024 | Modelling and drug targeting of a myeloid neoplasm with atypical 3q26/MECOM rearrangement using patient-specific iPSCs. | 0 |
| 35038958 | 2022 | MECOM gene overexpression in pediatric patients with acute myeloid leukemia. | 0 |
| 36861732 | 2023 | Validation 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 |
| 39853740 | 2025 | Mechanisms of enhancer-driven oncogene activation. | 0 |
| 37610030 | 2023 | A novel mutation in MECOM affects MPL regulation in vitro and results in thrombocytopenia and bone marrow failure. | 0 |
| 38086946 | 2024 | Preclinical efficacy of targeting epigenetic mechanisms in AML with 3q26 lesions and EVI1 overexpression. | 0 |
| 35044164 | 2022 | MeCOM: A Method for Comparing Three-Dimensional Metalloenzyme Active Sites. | 0 |
| 31109591 | 2019 | Deciphering the complexities of MECOM rearrangement-driven chromosomal aberrations. | 0 |
| 38440890 | 2024 | MECOM: a bioinformatics and experimentally identified marker for the diagnosis and prognosis of lung adenocarcinoma. | 0 |
| 32219447 | 2020 | Atypical 3q26/MECOM rearrangements genocopy inv(3)/t(3;3) in acute myeloid leukemia. | 0 |
| 36951195 | 2023 | Identifying prognostic gene panels in acute myeloid leukemia. | 0 |
| 34958895 | 2022 | EVI1 protein interaction dynamics: Targetable for therapeutic intervention? | 0 |
| 36095844 | 2023 | EVI1 drives leukemogenesis through aberrant ERG activation. | 0 |
| 38962996 | 2024 | Acute myeloid leukemia (AML) with chromosome 3 inversion: biology, management, and clinical outcome. | 0 |
| 39316992 | 2024 | Germline genetic variants that predispose to myeloproliferative neoplasms and hereditary myeloproliferative phenotypes. | 0 |
| 34404532 | 2021 | Congenital amegakaryocytic thrombocytopenia - Not a single disease. | 0 |
| 31554743 | 2019 | MECOM: A Very Interesting Gene Involved also in Lymphoid Malignancies. | 0 |
| 34668265 | 2022 | Comparison 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 |
| 35219593 | 2022 | MECOM-related disorder: Radioulnar synostosis without hematological aberration due to unique variants. | 0 |
| 38995475 | 2024 | CRISPR-Cas9-mediated deletion enhancer of MECOM play a tumor suppressor role in ovarian cancer. | 0 |
| 27438527 | 2016 | Molecular basis of inherited thrombocytopenias: an update. | 0 |
| 34974290 | 2022 | Newly designed breakapart FISH probe helps to identify cases with true MECOM rearrangement in myeloid malignancies. | 0 |
| 31820561 | 2020 | Two effects of GATA2 enhancer repositioning by 3q chromosomal rearrangements. | 0 |
| 36332568 | 2022 | Vade-MECOM: How to peel back the layers of hematopoiesis. | 0 |
| 22372463 | 2012 | BCR-ABL1 tyrosine kinase sustained MECOM expression in chronic myeloid leukaemia. | 0 |
| 37585491 | 2023 | Phase I Results of Bromodomain and Extra-Terminal Inhibitor PLX51107 in Combination with Azacitidine in Patients with Relapsed/Refractory Myeloid Malignancies. | 0 |
| 37996699 | 2024 | The urothelial gene regulatory network: understanding biology to improve bladder cancer management. | 0 |
| 39633068 | 2025 | HMX3 is a critical vulnerability in MECOM-negative KMT2A::MLLT3 acute myelomonocytic leukemia. | 0 |
| 29666008 | 2018 | H2AFY is a novel fusion partner of MECOM in acute myeloid leukemia. | 0 |
| 21569010 | 2011 | EVI1-mediated down regulation of MIR449A is essential for the survival of EVI1 positive leukaemic cells. | 0 |
| 26815134 | 2016 | Complex chromosomal rearrangements leading to MECOM overexpression are recurrent in myeloid malignancies with various 3q abnormalities. | 0 |
| 38811025 | 2024 | Evaluation 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 |
| 27620344 | 2017 | Intratumoral Heterogeneity of Frameshift Mutations in MECOM Gene is Frequent in Colorectal Cancers with High Microsatellite Instability. | 0 |
| 30503564 | 2019 | Molecular and pathologic characterization of AML with double Inv(3)(q21q26.2). | 0 |
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 8931999 | 1996 | Cytogenetic analysis in patients with primary myelodysplastic syndromes in leukaemic transformation. A report on 94 cases. Groupe Français de Cytogénétique Hématologique (GFCH). | |
| 6690021 | 1984 | Preliminary data on the in vitro proliferation pattern and karyotypic characteristics in cells of patients with ANLL. | Barbieri D et al |
| 7889504 | 1995 | Translocation (2;3)(p22;q28) is associated with myeloid disorders. | Berger R et al |
| 4063525 | 1985 | Rearrangements of chromosome 3 involving bands 3q21 and 3q26 are associated with normal or elevated platelet counts in acute nonlymphocytic leukemia. | Bitter MA et al |
| 11960392 | 2002 | Structural rearrangements of chromosome 3 in 57 patients with acute myeloid leukemia: clinical, hematological and cytogenetic features. | Charrin C et al |
| 2013977 | 1991 | Molecular 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 |
| 8625269 | 1996 | Translocation (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 |
| 10198625 | 1999 | Translocation (2;3)(p21;q26) as the sole anomaly in a case of primary myelofibrosis. | Herens C et al |
| 8683992 | 1996 | Abberant cytogenetic evolution pattern of Philadelphia-positive chronic myeloid leukemia treated with interferon-alpha. | Johansson B et al |
| 1555200 | 1992 | t(2;3)(p13;q26) in a case of chronic myeloid leukemia. Importance of the involvement of 3q26. | Kwong YL et al |
| 8616064 | 1996 | t(2;3)(p23;q26) in a patient with AML M2. | Levaltier X et al |
| 11964274 | 2002 | Distinct clinical outcomes for cytogenetic abnormalities evolving from aplastic anemia. | Maciejewski JP et al |
| 6575860 | 1983 | 3q-, 3q+ anomaly in malignant proliferations in humans. | Mecucci C et al |
| 11979548 | 2002 | Spectral 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 |
| 10779995 | 2000 | Secondary leukemia in a child with neuroblastoma while on oral etoposide: what is the cause? | Ng A et al |
| 7272506 | 1981 | Nonrandom chromosome abnormalities in acute leukemia and dysmyelopoietic syndromes in patients with previously treated malignant disease. | Rowley JD et al |
| 15085164 | 2004 | Translocation 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 |
| 3891074 | 1985 | The 5q-anomaly. | Van den Berghe H et al |
| 3337904 | 1988 | Cytogenetic studies in patients with secondary leukemia/dysmyelopoietic syndrome after different treatment modalities. | Whang-Peng J et al |
| 6692334 | 1984 | Recurrent chromosomal defects are found in most patients with acute nonlymphocytic leukemia. | Yunis JJ et al |
| 8652379 | 1996 | Cytogenetic 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.
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/t(2;3)(p15-23;q26-27)-mecom
Historical Card
2004-05-01 t(2;3)(p15-23;q26-27) ?/MECOM by Marian Stevens-Kroef Affiliation
Clinical Cytogeneticist, UMC St. Radboud, Dept. Human Genetics, Div. Cytogenetics, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands
