t(12;21)(p13;q22) ETV6/RUNX1
1997-08-01 Jean-Loup Huret , Alain Bernheim , Jean-Loup Huret Affiliation1.Laboratoire de Cytogénétique, UMR 1599 CNRS, Institut Gustave Roussy, 94805 Villejuif, France
2.Laboratoire de Cytogénétique, UMR 1599 CNRS, Institut Gustave Roussy, 94805 Villejuif, France
Clinics and Pathology
Disease
B cell ALL
Phenotype stem cell origin
L1 and L2, CD10+
Epidemiology
15 to 35% of paediatric B-lineage ALL: so far the mostfrequent translocation in this group; rare or absent in adults and ininfants; age: children; no case >20 yrs so far; male and female equallyrepresented
Clinics
standard ALL
Prognosis
CR in all cases; prognosis seems good
Cytogenetics
Cytogenetics morphological
t(12;21) often remained undetected
Cytogenetics molecular
easily detected by chromosomes 12 and 21 painting orspecific probes
Additional anomalies
frequent del(12)(p12) on the other chromosome; in rarecases duplication of der(21)t(12;21); looks like a +21
Variants
t(6;12;21), t(3;12;21)
Genes Involved and Proteins
Gene name
ETV6 (ets variant 6)
Location
12p13.2
Protein description
contains a HLH domain and a ETS-DNA binding domain;contains a Runt domain and, in the C-term, a
Gene name
RUNX1 (runt-related transcription factor 1 (acute myeloid leukemia 1; aml1 oncogene))
Location
21q22.12
Dna rna description
transcription is from telomere to centromere
Protein description
transactivation domain; forms heterodimers; widely expressed; nuclear
Protein description
localisation; transcription factor (activator) for various
Protein description
hematopoietic-specific genes
Result of the Chromosomal Anomaly
ETV6 (TEL) and RUNX1 (AML1) breakpoints in the t(12;21) / 5 ETV6 - 3 RUNX1 fusion gene - Courtesy Hossein Mossafa.
Description
TEL-AML1 chimaeric gene; 5 centromere to 3 telomere orientation
Transcript
the fusion transcript on chromosome 21 TEL -AML1 is the crucialone; the AML1-TEL transcript is absent in some cases; the other TEL alleleis often deleted.
Detection protocole
RT-PCR of the fusion transcript
Description
Helix loop helix of TEL fused to the nearly entire AML1
Description
protein, comprising the Runt domain and the transactivation domain
Highly cited references
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 28819864 | 2018 | Molecular processes involved in B cell acute lymphoblastic leukaemia. | 274 |
| 38203823 | 2024 | Germline Variants and Characteristic Features of Hereditary Hematological Malignancy Syndrome. | 260 |
| 32117272 | 2020 | Neoantigens in Hematologic Malignancies. | 183 |
| 33218352 | 2020 | Single cell characterization of B-lymphoid differentiation and leukemic cell states during chemotherapy in ETV6-RUNX1-positive pediatric leukemia identifies drug-targetable transcription factor activities. | 144 |
| 22823977 | 2012 | Myeloid malignancies: mutations, models and management. | 137 |
| 38999955 | 2024 | The Role of the JAK-STAT Pathway in Childhood B-Cell Acute Lymphoblastic Leukemia. | 130 |
| 28418909 | 2017 | Pathogenesis of ETV6/RUNX1-positive childhood acute lymphoblastic leukemia and mechanisms underlying its relapse. | 117 |
| 36766699 | 2023 | The Landscape of Secondary Genetic Rearrangements in Pediatric Patients with B-Cell Acute Lymphoblastic Leukemia with t(12;21). | 110 |
| 33038982 | 2020 | Molecular markers in ALL: Clinical implications. | 107 |
| 26085716 | 2015 | Prognostification of ALL by Cytogenetics. | 99 |
| 38777370 | 2024 | A multiomic characterization of the leukemia cell line REH using short- and long-read sequencing. | 88 |
| 30842058 | 2019 | Comparative features and outcomes between paediatric T-cell and B-cell acute lymphoblastic leukaemia. | 83 |
| 38136366 | 2023 | Generation of a Zebrafish Knock-In Model Recapitulating Childhood ETV6::RUNX1-Positive B-Cell Precursor Acute Lymphoblastic Leukemia. | 83 |
| 36350827 | 2023 | ETV6 Deficiency Unlocks ERG-Dependent Microsatellite Enhancers to Drive Aberrant Gene Activation in B-Lymphoblastic Leukemia. | 82 |
| 31902036 | 2020 | Insights into the prenatal origin of childhood acute lymphoblastic leukemia. | 82 |
| 33074527 | 2020 | Precision medicine in acute lymphoblastic leukemia. | 78 |
| 37019990 | 2023 | The KMT2A recombinome of acute leukemias in 2023. | 76 |
| 38968149 | 2024 | Single-cell genomics details the maturation block in BCP-ALL and identifies therapeutic vulnerabilities in DUX4-r cases. | 74 |
| 37019972 | 2023 | Etiology of oncogenic fusions in 5,190 childhood cancers and its clinical and therapeutic implication. | 71 |
| 36411286 | 2022 | Regulome analysis in B-acute lymphoblastic leukemia exposes Core Binding Factor addiction as a therapeutic vulnerability. | 71 |
| 26919255 | 2016 | Cooperation of ETV6/RUNX1 and BCL2 enhances immunoglobulin production and accelerates glomerulonephritis in transgenic mice. | 68 |
| 31779973 | 2019 | How advanced are we in targeting novel subtypes of ALL? | 68 |
| 37670323 | 2023 | RNA binding protein IGF2BP1 synergizes with ETV6-RUNX1 to drive oncogenic signaling in B-cell Acute Lymphoblastic Leukemia. | 65 |
| 38844578 | 2024 | ETV6::RUNX1 Acute Lymphoblastic Leukemia: how much therapy is needed for cure? | 62 |
| 27265895 | 2016 | Identification of ETV6-RUNX1-like and DUX4-rearranged subtypes in paediatric B-cell precursor acute lymphoblastic leukaemia. | 59 |
| 37469802 | 2023 | Optical Genome Mapping Identifies Novel Recurrent Structural Alterations in Childhood ETV6::RUNX1+ and High Hyperdiploid Acute Lymphoblastic Leukemia. | 59 |
| 26711002 | 2016 | Determination of ETV6-RUNX1 genomic breakpoint by next-generation sequencing. | 57 |
| 24339741 | 2013 | ETV6/RUNX1 induces reactive oxygen species and drives the accumulation of DNA damage in B cells. | 57 |
| 39880832 | 2025 | Molecular and pharmacological heterogeneity of ETV6::RUNX1 acute lymphoblastic leukemia. | 55 |
| 28408464 | 2017 | Targetable kinase gene fusions in high-risk B-ALL: a study from the Children's Oncology Group. | 54 |
| 32572036 | 2020 | Evidence for a role of RUNX1 as recombinase cofactor for TCRβ rearrangements and pathological deletions in ETV6-RUNX1 ALL. | 54 |
| 21628403 | 2011 | Modeling the evolution of ETV6-RUNX1-induced B-cell precursor acute lymphoblastic leukemia in mice. | 53 |
| 32693409 | 2021 | Molecular basis of ETV6-mediated predisposition to childhood acute lymphoblastic leukemia. | 50 |
| 39498293 | 2024 | Potential molecular mechanisms of ETV6-RUNX1-positive B progenitor cell cluster in acute lymphoblastic leukemia revealed by single-cell RNA sequencing. | 48 |
| 34250504 | 2021 | Clinical significance of novel subtypes of acute lymphoblastic leukemia in the context of minimal residual disease-directed therapy. | 46 |
| 39316653 | 2025 | Outcomes in patients with ETV6::RUNX1 or high-hyperdiploid B-ALL treated in the St. Jude Total Therapy XV/XVI studies. | 46 |
| 31952221 | 2020 | ETV6/RUNX1 Fusion Gene Abrogation Decreases the Oncogenicity of Tumour Cells in a Preclinical Model of Acute Lymphoblastic Leukaemia. | 46 |
| 22237106 | 2012 | The genetic basis of early T-cell precursor acute lymphoblastic leukaemia. | 43 |
| 30381299 | 2019 | Autophagy inhibition as a potential future targeted therapy for ETV6-RUNX1-driven B-cell precursor acute lymphoblastic leukemia. | 43 |
| 34101758 | 2021 | Investigation of lncRNA-mRNA co-expression network in ETV6-RUNX1-positive pediatric B-cell acute lymphoblastic leukemia. | 41 |
| 37153875 | 2023 | The Prognostic Effect of IKZF1 Deletions in ETV6::RUNX1 and High Hyperdiploid Childhood Acute Lymphoblastic Leukemia. | 41 |
| 39261601 | 2024 | Determinants of survival after first relapse of acute lymphoblastic leukemia: a Children's Oncology Group study. | 41 |
| 35685921 | 2022 | Low Prevalence of ETV6::RUNX1 Fusion Gene in a Hispanic Population. | 40 |
| 34988026 | 2021 | Prognostic Value and Outcome for ETV6/RUNX1-Positive Pediatric Acute Lymphoblastic Leukemia: A Report From the South China Children's Leukemia Group. | 40 |
| 34336858 | 2021 | The Second Oncogenic Hit Determines the Cell Fate of ETV6-RUNX1 Positive Leukemia. | 39 |
| 26580398 | 2015 | A Double Negative Loop Comprising ETV6/RUNX1 and MIR181A1 Contributes to Differentiation Block in t(12;21)-Positive Acute Lymphoblastic Leukemia. | 34 |
| 29254279 | 2017 | Modeling the process of childhood ETV6-RUNX1 B-cell leukemias. | 31 |
| 30487223 | 2018 | Transcriptional landscape of B cell precursor acute lymphoblastic leukemia based on an international study of 1,223 cases. | 31 |
| 27065576 | 2016 | Evaluation of ETV6/RUNX1 Fusion and Additional Abnormalities Involving ETV6 and/or RUNX1 Genes Using FISH Technique in Patients with Childhood Acute Lymphoblastic Leukemia. | 30 |
| 21869842 | 2012 | ETV6-RUNX1-positive childhood acute lymphoblastic leukemia: improved outcome with contemporary therapy. | 30 |
| 33677868 | 2021 | [Clinical features and prognosis of ETV6-RUNX1-positive childhood B-precursor acute lymphocyte leukemia]. | 29 |
| 28548470 | 2017 | Whole-Exome Sequencing of ETV6/RUNX1 in Four Childhood Acute Lymphoblastic Leukaemia Cases. | 29 |
| 30115129 | 2018 | ETV6/RUNX1-positive childhood acute lymphoblastic leukemia in China: excellent prognosis with improved BFM protocol. | 24 |
| 31085145 | 2019 | CD9 predicts ETV6-RUNX1 in childhood B-cell precursor acute lymphoblastic leukemia. | 22 |
| 33987955 | 2021 | RAG1 co-expression signature identifies ETV6-RUNX1-like B-cell precursor acute lymphoblastic leukemia in children. | 22 |
| 26269126 | 2015 | Somatic drivers of B-ALL in a model of ETV6-RUNX1; Pax5(+/-) leukemia. | 22 |
| 27506214 | 2017 | Outcome and Prognostic Factors for ETV6/RUNX1 Positive Pediatric Acute Lymphoblastic Leukemia Treated at a Single Institution in Korea. | 22 |
| 37969368 | 2023 | Coexistence of ETV6-RUNX1 and MLL aberration among pediatric acute lymphoblastic leukemia: case reports and a literature review. | 20 |
| 34535762 | 2022 | ETV6-RUNX1 and RUNX1 directly regulate RAG1 expression: one more step in the understanding of childhood B-cell acute lymphoblastic leukemia leukemogenesis. | 15 |
| 36741356 | 2023 | Cytokine Hyperresponsiveness in Children With ETV6::RUNX1-positive Acute Lymphoblastic Leukemia After Challenge With Common Pathogens. | 15 |
| 38243088 | 2024 | Ontogeny shapes the ability of ETV6::RUNX1 to enhance hematopoietic stem cell self-renewal and disrupt early lymphopoiesis. | 15 |
| 36226493 | 2023 | IL1RAP is expressed in several subtypes of pediatric acute lymphoblastic leukemia and can be used as a target to eliminate ETV6::RUNX1-positive leukemia cells in preclinical models. | 15 |
| 37345483 | 2023 | Impact of pinworm infection on the development of murine B-cell leukemia/lymphoma in the presence and absence of ETV6::RUNX1. | 14 |
| 36538046 | 2023 | ETS Fight Club on Microsatellite Enhancers. | 10 |
| 36045062 | 2023 | First Case of ETV6-RUNX1 Fusion in Adult De Novo Acute Myeloid Leukemia Detected Using Targeted RNA Sequencing. | 10 |
| 29108220 | 2017 | Minimal residual disease in pediatric ALL. | 8 |
| 28299659 | 2017 | Mechanism of ETV6-RUNX1 Leukemia. | 0 |
| 37120350 | 2023 | Emerging molecular subtypes and therapies in acute lymphoblastic leukemia. | 0 |
| 38824653 | 2024 | ETV6::RUNX1-like Acute Lymphoblastic Leukemia. | 0 |
| 28299660 | 2017 | ETV6-RUNX1 (+) Acute Lymphoblastic Leukaemia in Identical Twins. | 0 |
| 32836179 | 2020 | Siblings with ETV6/RUNX1-positive B-lymphoblastic leukemia: A single site experience and review of the literature. | 0 |
| 37407363 | 2023 | Transcription factor abnormalities in B-ALL leukemogenesis and treatment. | 0 |
| 28630052 | 2017 | Infection Exposure Promotes ETV6-RUNX1 Precursor B-cell Leukemia via Impaired H3K4 Demethylases. | 0 |
| 37157849 | 2023 | Cannibalism in an ETV6::RUNX1 paediatric B acute lymphoblastic leukaemia. | 0 |
| 28395118 | 2017 | ETV6/RUNX1-like acute lymphoblastic leukemia: A novel B-cell precursor leukemia subtype associated with the CD27/CD44 immunophenotype. | 0 |
| 28063378 | 2017 | Overexpression of PTP4A3 in ETV6-RUNX1 acute lymphoblastic leukemia. | 0 |
| 36565795 | 2023 | Fishing for ETV6/RUNX1 fusion and MLL gene rearrangements and their additional abnormalities in childhood acute lymphoblastic leukemia patients of Kashmir. | 0 |
| 31602594 | 2020 | The correction of ETV6/RUNX1 translocation in acute lymphocytic leukemia cells: a new gene targeting system by homologous recombination mechanism. | 0 |
| 29778230 | 2018 | ETV6/RUNX1-positive childhood acute lymphoblastic leukemia (ALL): The spectrum of clonal heterogeneity and its impact on prognosis. | 0 |
| 35506873 | 2022 | Apparent coexistence of ETV6::RUNX1 and KMT2A::MLLT3 fusions due to a nonproductive KMT2A rearrangement in B-ALL. | 0 |
| 24740533 | 2014 | False positivity of ETV6/RUNX1 detected by FISH in healthy newborns and adults. | 0 |
| 38490765 | 2024 | Germline predisposition to myeloid neoplasms: Characteristics and management of high versus variable penetrance disorders. | 0 |
| 26852652 | 2016 | ETV6/RUNX1 transcript is a target of RNA-binding protein IGF2BP1 in t(12;21)(p13;q22)-positive acute lymphoblastic leukemia. | 0 |
| 18728978 | 2008 | RUNX1 aberrations in ETV6/RUNX1-positive and ETV6/RUNX1-negative patients: its hemato-pathological and prognostic significance in a large cohort (619 cases) of ALL. | 0 |
| 25388957 | 2015 | Clonal origins of ETV6-RUNX1⁺ acute lymphoblastic leukemia: studies in monozygotic twins. | 0 |
| 38588489 | 2024 | Mutational and transcriptional landscape of pediatric B-cell precursor lymphoblastic lymphoma. | 0 |
| 21900195 | 2011 | ETV6-RUNX1 promotes survival of early B lineage progenitor cells via a dysregulated erythropoietin receptor. | 0 |
| 33400146 | 2021 | Emerging molecular subtypes and therapeutic targets in B-cell precursor acute lymphoblastic leukemia. | 0 |
| 30986496 | 2019 | ETV6-RUNX1 interacts with a region in SPIB intron 1 to regulate gene expression in pre-B-cell acute lymphoblastic leukemia. | 0 |
| 17325341 | 2007 | The identification of (ETV6)/RUNX1-regulated genes in lymphopoiesis using histone deacetylase inhibitors in ETV6/RUNX1-positive lymphoid leukemic cells. | 0 |
| 19100516 | 2009 | ETV6/RUNX1 fusion lacking prognostic effect in pediatric patients with acute lymphoblastic leukemia. | 0 |
| 20713965 | 2011 | Prevalence of t(12;21)[ETV6-RUNX1]-positive cells in healthy neonates. | 0 |
| 28778863 | 2017 | New oncogenic subtypes in pediatric B-cell precursor acute lymphoblastic leukemia. | 0 |
| 26625756 | 2015 | Low Frequency of ETV6-RUNX1 (t 12; 21) in Saudi Arabian Pediatric Acute Lymphoblastic Leukemia Patients: Association with Clinical Parameters and Early Remission. | 0 |
| 29408281 | 2018 | Tumor suppressor BTG1 limits activation of BCL6 expression downstream of ETV6-RUNX1. | 0 |
| 24596209 | 2014 | ETV6-RUNX1-positive ALL may be driven by aberrant RAG activity. | 0 |
| 16213362 | 2005 | Detection of ETV6 and RUNX1 gene rearrangements using fluorescence in situ hybridization in Mexican patients with acute lymphoblastic leukemia: experience at a single institution. | 0 |
| 38215390 | 2024 | CD371-positive pediatric B-cell acute lymphoblastic leukemia: propensity to lineage switch and slow early response to treatment. | 0 |
| 15704129 | 2005 | ETV6/RUNX1 fusion at diagnosis and relapse: some prognostic indications. | 0 |
| 18767247 | 2008 | Leukemia/lymphoma-associated gene fusions in normal individuals. | 0 |
Bibliography
No bibliography items were found for this article.
Summary
Fusion gene
ETV6/RUNX1 ETV6 (12p13.2) RUNX1 (21q22.12) M +der(21)t(12;21)(p13;q22) del(12)(p13p13) ins(12;21)(p13;q22q22) t(11;12;21)(q14;p13;q22) t(12;21)(p13;q22) t(2;12;21)(q33;p13;q22)|ETV6/RUNX1 ETV6 (12p13.2) RUNX1 (21q22.12) TIC
t(12;21)(p13;q22) ETV6/RUNX1 Top : Hybridization with Vysis LSI ETV6/RUNX1 dual color probe (Abbott Molecular, US) showing fused yellow signals on der(12) and der(21) chromosomes (A) and with simultaneous ETV6 deletion (B) - Courtesy Adriana Zamecnikova. t(12;21)(p13;q22) R- bandind and FISH - Courtesy Hossein Mossafa.
Citation
Jean-Loup Huret ; Alain Bernheim ; Jean-Loup Huret
t(12;21)(p13;q22) ETV6/RUNX1
Atlas Genet Cytogenet Oncol Haematol. 1997-08-01
Online version: http://atlasgeneticsoncology.org/haematological/1073/t(12;21)(p13;q22)-etv6-runx1
