inv(3)(p24q26) ?/MECOM
2016-07-01 Jean Loup Huret Affiliation1.Medical Genetics, Dept Medical Information, University Hospital, F-86021 Poitiers, France. [email protected]
Abstract
Review on inv(3)(p24q26), with data on clinics, and the genes involved.
Clinics and Pathology
Noted
Ten cases available, but with almost no data (Haferlach et al., 2012).
Phenotype stem cell origin
Out of ten cases, there were eight acute myeloid leukemia (AML) cases, and two myelodysplastic syndromes (MDS)
Epidemiology
inv(3)(p24q26) represented about 1% of a cohort of 606 AML and 377 MDS patients with normal karyotypes (n = 594) or chromosome 7 alterations (-7/7q-; n = 389). Median age was 60 years (range 20-76)
Cytogenetics
Cryptic rearrangement.
Prognosis
Survival outcomes in 22 patients with cryptic MECOM rearrangements (inv(3)(p24q26), t(3;21)(q26;q11), and der(7)t(3;7)(q26;q21) altogether) and were compared with inv(3)(q21q26)/t(3;3)(q21;q26) cases. Median overall survival was 9.4 months in the subgroup with cryptic MECOM rearrangements which was not significantly different from the 21.8 months in patients with an inv(3)(q21q26)/t(3;3)(q21;q26)
Genes Involved and Proteins
Note
The partner of MECOM is unknown.
Gene name
MECOM (Ecotropic Viral Integration Site 1 (EVI1) and Myelodysplastic Syndrome 1 (MDS1-EVI1)
Location
3q26.2
Note
MECOM is a nuclear transcription factor that plays an essential role in the proliferation and maintenance of hematopoietic stem cells and can inhibit myeloid differentiation. Two alternative forms exists, one generated from EVI1, the other MECOM (MDS1 and EVI1 complex locus) through intergenic splicing with MDS1 (myelodysplasia syndrome 1), a gene located 140 kb upstream of EVI1.
Protein description
The protein encoded by this gene is a transcriptional regulator involved in cell differentiation and proliferation, and apoptosis. The encoded protein can interact with transcriptional coactivators (P/CAF, CBP) and corepressors (CTBP1, HDAC) as well as other transcription factors (GATA1, Smad3) (de Braekeleer et al., 2012)
Result of the Chromosomal Anomaly
Oncogenesis
Increased MECOM expression was noted.
Highly cited references
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
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| 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 |
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| 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 |
| 39468462 | 2024 | MECOM and the PRDM gene family in uterine endometrial cancer: bioinformatics and experimental insights into pathogenesis and therapeutic potentials. | 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 |
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| 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 |
| 23349225 | 2013 | Meta-analysis identifies a MECOM gene as a novel predisposing factor of osteoporotic fracture. | 49 |
| 39103556 | 2024 | An activity-regulated transcriptional program directly drives synaptogenesis. | 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 |
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| 39576394 | 2024 | Systematic pan-cancer analysis of the prognostic value of MECOM in human cancer. | 33 |
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| 37067177 | 2023 | Expanded phenotypic and hematologic abnormalities beyond bone marrow failure in MECOM-associated syndromes. | 32 |
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| 24309209 | 2014 | Zebrafish nephrogenesis is regulated by interactions between retinoic acid, mecom, and Notch signaling. | 29 |
| 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 |
| 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 |
| 38751957 | 2024 | A rare presentation of BCR-ABL1 and RUNX1-MECOM rearrangement in a pediatric patient with acute myeloid leukemia. | 17 |
| 35020829 | 2022 | Phenotypic heterogeneity in individuals with MECOM variants in 2 families. | 17 |
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| 31193989 | 2019 | Data on MECOM rearrangement-driven chromosomal aberrations in myeloid malignancies. | 9 |
| 37407873 | 2023 | MECOM Deficiency: from Bone Marrow Failure to Impaired B-Cell Development. | 0 |
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| 28409341 | 2017 | Zebrafish Pronephros Development. | 0 |
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| 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 |
| 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 |
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| 36951195 | 2023 | Identifying prognostic gene panels in acute myeloid leukemia. | 0 |
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| 34404532 | 2021 | Congenital amegakaryocytic thrombocytopenia - Not a single disease. | 0 |
| 35219593 | 2022 | MECOM-related disorder: Radioulnar synostosis without hematological aberration due to unique variants. | 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 |
| 31109591 | 2019 | Deciphering the complexities of MECOM rearrangement-driven chromosomal aberrations. | 0 |
| 38995475 | 2024 | CRISPR-Cas9-mediated deletion enhancer of MECOM play a tumor suppressor role in ovarian cancer. | 0 |
| 31554743 | 2019 | MECOM: A Very Interesting Gene Involved also in Lymphoid Malignancies. | 0 |
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| 36332568 | 2022 | Vade-MECOM: How to peel back the layers of hematopoiesis. | 0 |
| 34974290 | 2022 | Newly designed breakapart FISH probe helps to identify cases with true MECOM rearrangement in myeloid malignancies. | 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 |
| 22372463 | 2012 | BCR-ABL1 tyrosine kinase sustained MECOM expression in chronic myeloid leukaemia. | 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 |
| 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 |
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 22887804 | 2012 | Three novel cytogenetically cryptic EVI1 rearrangements associated with increased EVI1 expression and poor prognosis identified in 27 acute myeloid leukemia cases. | Haferlach C et al |
Summary
Fusion gene
?/MECOM
Citation
Jean Loup Huret
inv(3)(p24q26) ?/MECOM
Atlas Genet Cytogenet Oncol Haematol. 2016-07-01
Online version: http://atlasgeneticsoncology.org/haematological/1441/inv(3)(p24q26)-mecom
