t(12;21)(p13;q22) ETV6/RUNX1

1997-08-01   Jean-Loup Huret  , Alain Bernheim  , Jean-Loup Huret  

1.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

Atlas Image
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 IDYearTitleCitations
288198642018Molecular processes involved in B cell acute lymphoblastic leukaemia.274
382038232024Germline Variants and Characteristic Features of Hereditary Hematological Malignancy Syndrome.260
321172722020Neoantigens in Hematologic Malignancies.183
332183522020Single 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
228239772012Myeloid malignancies: mutations, models and management.137
389999552024The Role of the JAK-STAT Pathway in Childhood B-Cell Acute Lymphoblastic Leukemia.130
284189092017Pathogenesis of ETV6/RUNX1-positive childhood acute lymphoblastic leukemia and mechanisms underlying its relapse.117
367666992023The Landscape of Secondary Genetic Rearrangements in Pediatric Patients with B-Cell Acute Lymphoblastic Leukemia with t(12;21).110
330389822020Molecular markers in ALL: Clinical implications.107
260857162015Prognostification of ALL by Cytogenetics.99
387773702024A multiomic characterization of the leukemia cell line REH using short- and long-read sequencing.88
308420582019Comparative features and outcomes between paediatric T-cell and B-cell acute lymphoblastic leukaemia.83
381363662023Generation of a Zebrafish Knock-In Model Recapitulating Childhood ETV6::RUNX1-Positive B-Cell Precursor Acute Lymphoblastic Leukemia.83
363508272023ETV6 Deficiency Unlocks ERG-Dependent Microsatellite Enhancers to Drive Aberrant Gene Activation in B-Lymphoblastic Leukemia.82
319020362020Insights into the prenatal origin of childhood acute lymphoblastic leukemia.82
330745272020Precision medicine in acute lymphoblastic leukemia.78
370199902023The KMT2A recombinome of acute leukemias in 2023.76
389681492024Single-cell genomics details the maturation block in BCP-ALL and identifies therapeutic vulnerabilities in DUX4-r cases.74
370199722023Etiology of oncogenic fusions in 5,190 childhood cancers and its clinical and therapeutic implication.71
364112862022Regulome analysis in B-acute lymphoblastic leukemia exposes Core Binding Factor addiction as a therapeutic vulnerability.71
269192552016Cooperation of ETV6/RUNX1 and BCL2 enhances immunoglobulin production and accelerates glomerulonephritis in transgenic mice.68
317799732019How advanced are we in targeting novel subtypes of ALL?68
376703232023RNA binding protein IGF2BP1 synergizes with ETV6-RUNX1 to drive oncogenic signaling in B-cell Acute Lymphoblastic Leukemia.65
388445782024ETV6::RUNX1 Acute Lymphoblastic Leukemia: how much therapy is needed for cure?62
272658952016Identification of ETV6-RUNX1-like and DUX4-rearranged subtypes in paediatric B-cell precursor acute lymphoblastic leukaemia.59
374698022023Optical Genome Mapping Identifies Novel Recurrent Structural Alterations in Childhood ETV6::RUNX1+ and High Hyperdiploid Acute Lymphoblastic Leukemia.59
267110022016Determination of ETV6-RUNX1 genomic breakpoint by next-generation sequencing.57
243397412013ETV6/RUNX1 induces reactive oxygen species and drives the accumulation of DNA damage in B cells.57
398808322025Molecular and pharmacological heterogeneity of ETV6::RUNX1 acute lymphoblastic leukemia.55
284084642017Targetable kinase gene fusions in high-risk B-ALL: a study from the Children's Oncology Group.54
325720362020Evidence for a role of RUNX1 as recombinase cofactor for TCRβ rearrangements and pathological deletions in ETV6-RUNX1 ALL.54
216284032011Modeling the evolution of ETV6-RUNX1-induced B-cell precursor acute lymphoblastic leukemia in mice.53
326934092021Molecular basis of ETV6-mediated predisposition to childhood acute lymphoblastic leukemia.50
394982932024Potential molecular mechanisms of ETV6-RUNX1-positive B progenitor cell cluster in acute lymphoblastic leukemia revealed by single-cell RNA sequencing.48
342505042021Clinical significance of novel subtypes of acute lymphoblastic leukemia in the context of minimal residual disease-directed therapy.46
393166532025Outcomes in patients with ETV6::RUNX1 or high-hyperdiploid B-ALL treated in the St. Jude Total Therapy XV/XVI studies.46
319522212020ETV6/RUNX1 Fusion Gene Abrogation Decreases the Oncogenicity of Tumour Cells in a Preclinical Model of Acute Lymphoblastic Leukaemia.46
222371062012The genetic basis of early T-cell precursor acute lymphoblastic leukaemia.43
303812992019Autophagy inhibition as a potential future targeted therapy for ETV6-RUNX1-driven B-cell precursor acute lymphoblastic leukemia.43
341017582021Investigation of lncRNA-mRNA co-expression network in ETV6-RUNX1-positive pediatric B-cell acute lymphoblastic leukemia.41
371538752023The Prognostic Effect of IKZF1 Deletions in ETV6::RUNX1 and High Hyperdiploid Childhood Acute Lymphoblastic Leukemia.41
392616012024Determinants of survival after first relapse of acute lymphoblastic leukemia: a Children's Oncology Group study.41
356859212022Low Prevalence of ETV6::RUNX1 Fusion Gene in a Hispanic Population.40
349880262021Prognostic Value and Outcome for ETV6/RUNX1-Positive Pediatric Acute Lymphoblastic Leukemia: A Report From the South China Children's Leukemia Group.40
343368582021The Second Oncogenic Hit Determines the Cell Fate of ETV6-RUNX1 Positive Leukemia.39
265803982015A Double Negative Loop Comprising ETV6/RUNX1 and MIR181A1 Contributes to Differentiation Block in t(12;21)-Positive Acute Lymphoblastic Leukemia.34
292542792017Modeling the process of childhood ETV6-RUNX1 B-cell leukemias.31
304872232018Transcriptional landscape of B cell precursor acute lymphoblastic leukemia based on an international study of 1,223 cases.31
270655762016Evaluation of ETV6/RUNX1 Fusion and Additional Abnormalities Involving ETV6 and/or RUNX1 Genes Using FISH Technique in Patients with Childhood Acute Lymphoblastic Leukemia.30
218698422012ETV6-RUNX1-positive childhood acute lymphoblastic leukemia: improved outcome with contemporary therapy.30
336778682021[Clinical features and prognosis of ETV6-RUNX1-positive childhood B-precursor acute lymphocyte leukemia].29
285484702017Whole-Exome Sequencing of ETV6/RUNX1 in Four Childhood Acute Lymphoblastic Leukaemia Cases.29
301151292018ETV6/RUNX1-positive childhood acute lymphoblastic leukemia in China: excellent prognosis with improved BFM protocol.24
310851452019CD9 predicts ETV6-RUNX1 in childhood B-cell precursor acute lymphoblastic leukemia.22
339879552021RAG1 co-expression signature identifies ETV6-RUNX1-like B-cell precursor acute lymphoblastic leukemia in children.22
262691262015Somatic drivers of B-ALL in a model of ETV6-RUNX1; Pax5(+/-) leukemia.22
275062142017Outcome and Prognostic Factors for ETV6/RUNX1 Positive Pediatric Acute Lymphoblastic Leukemia Treated at a Single Institution in Korea.22
379693682023Coexistence of ETV6-RUNX1 and MLL aberration among pediatric acute lymphoblastic leukemia: case reports and a literature review.20
345357622022ETV6-RUNX1 and RUNX1 directly regulate RAG1 expression: one more step in the understanding of childhood B-cell acute lymphoblastic leukemia leukemogenesis.15
367413562023Cytokine Hyperresponsiveness in Children With ETV6::RUNX1-positive Acute Lymphoblastic Leukemia After Challenge With Common Pathogens.15
382430882024Ontogeny shapes the ability of ETV6::RUNX1 to enhance hematopoietic stem cell self-renewal and disrupt early lymphopoiesis.15
362264932023IL1RAP 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
373454832023Impact of pinworm infection on the development of murine B-cell leukemia/lymphoma in the presence and absence of ETV6::RUNX1.14
365380462023ETS Fight Club on Microsatellite Enhancers.10
360450622023First Case of ETV6-RUNX1 Fusion in Adult De Novo Acute Myeloid Leukemia Detected Using Targeted RNA Sequencing.10
291082202017Minimal residual disease in pediatric ALL.8
282996592017Mechanism of ETV6-RUNX1 Leukemia.0
371203502023Emerging molecular subtypes and therapies in acute lymphoblastic leukemia.0
388246532024ETV6::RUNX1-like Acute Lymphoblastic Leukemia.0
282996602017ETV6-RUNX1 (+) Acute Lymphoblastic Leukaemia in Identical Twins.0
328361792020Siblings with ETV6/RUNX1-positive B-lymphoblastic leukemia: A single site experience and review of the literature.0
374073632023Transcription factor abnormalities in B-ALL leukemogenesis and treatment.0
286300522017Infection Exposure Promotes ETV6-RUNX1 Precursor B-cell Leukemia via Impaired H3K4 Demethylases.0
371578492023Cannibalism in an ETV6::RUNX1 paediatric B acute lymphoblastic leukaemia.0
283951182017ETV6/RUNX1-like acute lymphoblastic leukemia: A novel B-cell precursor leukemia subtype associated with the CD27/CD44 immunophenotype.0
280633782017Overexpression of PTP4A3 in ETV6-RUNX1 acute lymphoblastic leukemia.0
365657952023Fishing for ETV6/RUNX1 fusion and MLL gene rearrangements and their additional abnormalities in childhood acute lymphoblastic leukemia patients of Kashmir.0
316025942020The correction of ETV6/RUNX1 translocation in acute lymphocytic leukemia cells: a new gene targeting system by homologous recombination mechanism.0
297782302018ETV6/RUNX1-positive childhood acute lymphoblastic leukemia (ALL): The spectrum of clonal heterogeneity and its impact on prognosis.0
355068732022Apparent coexistence of ETV6::RUNX1 and KMT2A::MLLT3 fusions due to a nonproductive KMT2A rearrangement in B-ALL.0
247405332014False positivity of ETV6/RUNX1 detected by FISH in healthy newborns and adults.0
384907652024Germline predisposition to myeloid neoplasms: Characteristics and management of high versus variable penetrance disorders.0
268526522016ETV6/RUNX1 transcript is a target of RNA-binding protein IGF2BP1 in t(12;21)(p13;q22)-positive acute lymphoblastic leukemia.0
187289782008RUNX1 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
253889572015Clonal origins of ETV6-RUNX1⁺ acute lymphoblastic leukemia: studies in monozygotic twins.0
385884892024Mutational and transcriptional landscape of pediatric B-cell precursor lymphoblastic lymphoma.0
219001952011ETV6-RUNX1 promotes survival of early B lineage progenitor cells via a dysregulated erythropoietin receptor.0
334001462021Emerging molecular subtypes and therapeutic targets in B-cell precursor acute lymphoblastic leukemia.0
309864962019ETV6-RUNX1 interacts with a region in SPIB intron 1 to regulate gene expression in pre-B-cell acute lymphoblastic leukemia.0
173253412007The identification of (ETV6)/RUNX1-regulated genes in lymphopoiesis using histone deacetylase inhibitors in ETV6/RUNX1-positive lymphoid leukemic cells.0
191005162009ETV6/RUNX1 fusion lacking prognostic effect in pediatric patients with acute lymphoblastic leukemia.0
207139652011Prevalence of t(12;21)[ETV6-RUNX1]-positive cells in healthy neonates.0
287788632017New oncogenic subtypes in pediatric B-cell precursor acute lymphoblastic leukemia.0
266257562015Low Frequency of ETV6-RUNX1 (t 12; 21) in Saudi Arabian Pediatric Acute Lymphoblastic Leukemia Patients: Association with Clinical Parameters and Early Remission.0
294082812018Tumor suppressor BTG1 limits activation of BCL6 expression downstream of ETV6-RUNX1.0
245962092014ETV6-RUNX1-positive ALL may be driven by aberrant RAG activity.0
162133622005Detection of ETV6 and RUNX1 gene rearrangements using fluorescence in situ hybridization in Mexican patients with acute lymphoblastic leukemia: experience at a single institution.0
382153902024CD371-positive pediatric B-cell acute lymphoblastic leukemia: propensity to lineage switch and slow early response to treatment.0
157041292005ETV6/RUNX1 fusion at diagnosis and relapse: some prognostic indications.0
187672472008Leukemia/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
Atlas Image
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