t(8;21)(q22;q22) RUNX1/RUNX1T1
2016-05-01 Wilma Kroes , Wilma Kroes Affiliation1.Department of Clinical Genetics, Leiden University Medical Center, Leiden; Department of Human Genetics, Radboud university medical center, Nijmegen, The Netherlands. [email protected]; [email protected]
2.Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France
Clinics and Pathology
Disease
Acute myeloid leukemia (AML) with t(8;21)(q22;q22) is part of the Group of AML with recurrent genetic abnormalities.
Phenotype stem cell origin
M2 mostly, rarely: M1 or M4
Epidemiology
Annual incidence: 1/106; 5% of AML, 10% of prior AML M2 (FAB classification). The most frequent anomaly in chilhood AML; seen in children and adults: mean age 30yrs, rare in elderly patients.
Clinics
Myeloid sarcomas may be present at presentation.
Translocation t(8;21) is found in 5-12% of AML. Among the non-random chromosomal aberrations observed in AML, t(8;21)(q22;q22) is one of the best known and usually correlates with AML M2, with well defined and specific morphological features. The common morphological features include the presence of large blast cells with abundant basophilic cytoplasm, often containing numerous azurophilic granulations; few blasts in some cases show very large granules (pseudo-Chediak-Higashi granules), suggesting abnormal fusion. Auer rods are frequently found. In addition to the large blast cells, there are also some smaller blasts, predominantly found in the peripheral blood. Promyelocytes, myelocytes and mature granulocytes with variable dysplasia are seen in the bone marrow. These cells may show abnormal nuclear segmentation and/or cytoplasmic staining defects including homogeneous pink colored cytoplasm - Text and iconography Courtesy Georges Flandrin 2001.
Cytology
See figure and legend.
Prognosis
Complete remission (CR) in most cases (90%) with relatively long disease-free survival when treated with high dose chemotherapy.
Cytogenetics
t(8;21)(q22;q22) : cohybridization experiments using dJ155L8 (RUNX1T1) and dJ1107L6 (RUNX1 ); note the splitting of RUNX1 and colocalization on der(8) with RUNX1T1 - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.
Cytogenetics molecular
Cases with cryptic molecular translocation have been detected --> FISH use may be relevant.
Additional anomalies
Sole anomaly in only 20-30%; additional anomalies: loss of Y or X chromosome in half cases (1 X must be present), del(7q) or -7, +8, del (9q): 10% each.
Variants
Complex t(8;21;Var) involving a (variable) third chromosome have been described in 3%; part from chromosome 21 goes on der(8), part of the 8 on der (Var), and part of Var on der(21); therefore, the crucial event lies on der(8).
Genes Involved and Proteins
Gene name
RUNX1T1 (runt-related transcription factor 1; translocated to, 1 (cyclin D-related))
Location
8q21.3
Dna rna description
Transcription is from telomere to centromere.
Protein description
3 proline rich domains, 2 Zn fingers, and in C-term, a PEST region; tissue restricted expression; nuclear localisation; putative transcription factor.
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
Contains a Runt domain and, in the C-term, a transactivation domain; forms heterodimers; widely expressed; nuclear localisation; transcription factor (activator) for various hematopoietic-specific genes.
Result of the Chromosomal Anomaly
RUNX1 and RUNX1T1 breakpoints in the t(8;21) / 5 RUNX1 - 3 RUNX1T1 fusion gene, and FISH - Courtesy Hossein Mossafa.
Description
5 RUNX1 - 3 RUNX1T1; breakpoints: at the very 5 end of RUNX1T1, between exons 5 and 6 in RUNX1.
Detection protocole
Karyotyping, RT-PCR and FISH for cases of typical cell morphology, but apparently without the t(8;21); RT-PCR for minimal residual disease detection
Description
The N-term runt domain from RUNX1 is fused to the 577 C-term residues from RUNX1T1; reciprocal product not detected; probable DNA binding role; the fusion protein retains the ability to recognize the RUNX1 concensus binding site (--> negative dominant competitor with the normal RUNX1) and to dimerize with the CBFb subunit.
Oncogenesis
Probable altered transcriptional regulation of normal RUNX1 target genes.
Highly cited references
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 34945003 | 2021 | PARP Inhibitors and Myeloid Neoplasms: A Double-Edged Sword. | 242 |
| 35065680 | 2022 | Targeting PARP proteins in acute leukemia: DNA damage response inhibition and therapeutic strategies. | 172 |
| 31817911 | 2019 | Core Binding Factor Leukemia: Chromatin Remodeling Moves Towards Oncogenic Transcription. | 150 |
| 36068610 | 2022 | ASXL1/2 mutations and myeloid malignancies. | 129 |
| 38061017 | 2023 | Proteogenomic analysis reveals cytoplasmic sequestration of RUNX1 by the acute myeloid leukemia-initiating CBFB::MYH11 oncofusion protein. | 112 |
| 36980682 | 2023 | Deregulated Gene Expression Profiles and Regulatory Networks in Adult and Pediatric RUNX1/RUNX1T1-Positive AML Patients. | 103 |
| 31935293 | 2020 | An update on the molecular pathogenesis and potential therapeutic targeting of AML with t(8;21)(q22;q22.1);RUNX1-RUNX1T1. | 101 |
| 39177514 | 2024 | Mutational cooperativity of RUNX1::RUNX1T1 isoform 9a and oncogenic NRAS in zebrafish myeloid leukaemia. | 96 |
| 33928020 | 2021 | Characteristics of Cohesin Mutation in Acute Myeloid Leukemia and Its Clinical Significance. | 87 |
| 36874378 | 2023 | Therapy-related core binding factor acute myeloid leukemia. | 86 |
| 33217477 | 2021 | The RUNX1/RUNX1T1 network: translating insights into therapeutic options. | 83 |
| 35563085 | 2022 | Mutated KIT Tyrosine Kinase as a Novel Molecular Target in Acute Myeloid Leukemia. | 82 |
| 34766123 | 2020 | Modelling t(8;21) acute myeloid leukaemia - What have we learned? | 80 |
| 27798625 | 2016 | The genomic landscape of core-binding factor acute myeloid leukemias. | 79 |
| 37019972 | 2023 | Etiology of oncogenic fusions in 5,190 childhood cancers and its clinical and therapeutic implication. | 71 |
| 33483506 | 2021 | RUNX1/RUNX1T1 mediates alternative splicing and reorganises the transcriptional landscape in leukemia. | 70 |
| 39243082 | 2024 | Identifying ADGRG1 as a specific marker for tumor-reactive T cells in acute myeloid leukemia. | 62 |
| 35902872 | 2022 | RUNX1T1 function in cell fate. | 61 |
| 37841755 | 2023 | CSF3R T618I Collaborates With RUNX1-RUNX1T1 to Expand Hematopoietic Progenitors and Sensitizes to GLI Inhibition. | 61 |
| 20589720 | 2010 | RUNX1 repression-independent mechanisms of leukemogenesis by fusion genes CBFB-MYH11 and AML1-ETO (RUNX1-RUNX1T1). | 57 |
| 38454121 | 2024 | Functional characterization of cooperating MGA mutations in RUNX1::RUNX1T1 acute myeloid leukemia. | 55 |
| 37790524 | 2023 | Functional Characterization of Cooperating MGA Mutations in RUNX1::RUNX1T1 Acute Myeloid Leukemia. | 55 |
| 35070977 | 2021 | Preemptive Immunotherapy for Minimal Residual Disease in Patients With t(8;21) Acute Myeloid Leukemia After Allogeneic Hematopoietic Stem Cell Transplantation. | 52 |
| 35973983 | 2022 | Phenotypically-defined stages of leukemia arrest predict main driver mutations subgroups, and outcome in acute myeloid leukemia. | 52 |
| 37464068 | 2023 | Dual intron-targeted CRISPR-Cas9-mediated disruption of the AML RUNX1-RUNX1T1 fusion gene effectively inhibits proliferation and decreases tumor volume in vitro and in vivo. | 50 |
| 30959925 | 2019 | Elucidation of Novel Therapeutic Targets for Acute Myeloid Leukemias with RUNX1-RUNX1T1 Fusion. | 48 |
| 36442087 | 2022 | Transcriptome-based molecular subtypes and differentiation hierarchies improve the classification framework of acute myeloid leukemia. | 47 |
| 35326705 | 2022 | CDK6 Degradation Is Counteracted by p16(INK4A) and p18(INK4C) in AML. | 42 |
| 28536267 | 2017 | The ubiquitin ligase STUB1 regulates stability and activity of RUNX1 and RUNX1-RUNX1T1. | 41 |
| 38427924 | 2024 | Targeting Molecular Measurable Residual Disease and Low-Blast Relapse in AML With Venetoclax and Low-Dose Cytarabine: A Prospective Phase II Study (VALDAC). | 37 |
| 38017299 | 2024 | Combination of eriocalyxin B and homoharringtonine exerts synergistic anti-tumor effects against t(8;21) AML. | 37 |
| 33477584 | 2021 | Prognostic Impacts of D816V KIT Mutation and Peri-Transplant RUNX1-RUNX1T1 MRD Monitoring on Acute Myeloid Leukemia with RUNX1-RUNX1T1. | 36 |
| 30050054 | 2018 | Mediation analysis reveals common mechanisms of RUNX1 point mutations and RUNX1/RUNX1T1 fusions influencing survival of patients with acute myeloid leukemia. | 36 |
| 31899799 | 2020 | Prospective evaluation of prognostic impact of KIT mutations on acute myeloid leukemia with RUNX1-RUNX1T1 and CBFB-MYH11. | 33 |
| 32115572 | 2020 | ZBTB7A prevents RUNX1-RUNX1T1-dependent clonal expansion of human hematopoietic stem and progenitor cells. | 32 |
| 24783204 | 2014 | RNA sequencing reveals upregulation of RUNX1-RUNX1T1 gene signatures in clear cell renal cell carcinoma. | 32 |
| 35445594 | 2022 | Comprehensive Mutation Profile in Acute Myeloid Leukemia Patients with RUNX1-RUNX1T1 or CBFB-MYH11 Fusions. | 31 |
| 32757686 | 2020 | Machine learning derived genomics driven prognostication for acute myeloid leukemia with RUNX1-RUNX1T1. | 29 |
| 39154170 | 2024 | Transformation into acute myeloid leukemia with t(8;21)(q22;q22.1); RUNX1::RUNX1T1 from JAK2-mutated essential thrombocythemia: a case report. | 29 |
| 28166825 | 2017 | The dynamics of RUNX1-RUNX1T1 transcript levels after allogeneic hematopoietic stem cell transplantation predict relapse in patients with t(8;21) acute myeloid leukemia. | 28 |
| 31723813 | 2019 | Molecular characterization of AML with RUNX1-RUNX1T1 at diagnosis and relapse reveals net loss of co-mutations. | 28 |
| 34921223 | 2021 | Epigenetic silencing of UBXN8 contributes to leukemogenesis in t(8;21) acute myeloid leukemia. | 25 |
| 38802593 | 2024 | Pediatric acute myeloid leukemia with t(8;21) and KIT mutation treatment with avapritinib post-stem cell transplantation: a report of four cases. | 25 |
| 28395444 | 2017 | [Prognostic value of dynamic monitoring of RUNX1-RUNX1T1 transcript in pediatric acute myeloid leukemia]. | 21 |
| 35765876 | 2022 | Immunohistochemical Staining to Identify Concomitant Systemic Mastocytosis in Acute Myeloid Leukemia with RUNX1::RUNX1T1. | 20 |
| 36833323 | 2023 | Fusion Gene-Based Classification of Variant Cytogenetic Rearrangements in Acute Myeloid Leukemia. | 20 |
| 38964927 | 2024 | [Two cases of systemic mastocytosis with RUNX1-RUNX1T1 positive acute myeloid leukemia treated with sequential avapritinib after allogeneic hematopoietic stem cell transplantation and literature review]. | 20 |
| 39735012 | 2024 | Characterization of Acute Myeloid Leukemia With RUNX1/RUNX1T1 Gene Rearrangement: Clinical, Hematological, and Morphological Features. | 19 |
| 34148054 | 2021 | RUNX1-ETO (RUNX1-RUNX1T1) induces myeloid leukemia in mice in an age-dependent manner. | 15 |
| 37621071 | 2023 | Co-existence of RUNX1-RUNX1T1 and BCR-ABL1 in acute myeloid leukemia: a case report. | 15 |
| 38012154 | 2023 | Venetoclax plus hypomethylating agents in newly diagnosed acute myeloid leukemia patients with RUNX1::RUNX1T1: a retrospective propensity score matching study. | 15 |
| 39234860 | 2025 | Adverse prognostic impact of KIT exon 17 mutations despite negative flow cytometric measurable residual disease in pediatric acute myeloid leukemia with RUNX1::RUNX1T1. | 15 |
| 35845276 | 2021 | Volunteer unrelated donor cell-derived acute myeloid leukemia with RUNX1-RUNX1T1. | 15 |
| 31856435 | 2019 | [An interlaboratory comparison study on the detection of RUNX1-RUNX1T1 fusion transcript levels and WT1 transcript levels]. | 15 |
| 30623623 | 2019 | Reclassification of Acute Myeloid Leukemia According to the 2016 WHO Classification. | 13 |
| 36369483 | 2022 | Not only mutations but also tumorigenesis can be substantially attributed to DNA damage from reactive oxygen species in RUNX1::RUNX1T1-fusion-positive acute myeloid leukemia. | 11 |
| 38633925 | 2024 | RUNX1::RUNX1T1 Acute Myeloid Leukemia Cytogenetically Showing t(6;8)(p23;q22). | 8 |
| 37519108 | 2023 | Hemophagocytic Lymphohistiocytosis in RUNX1::RUNX1T1 Positive AML with Blast Count Below 20%. | 4 |
| 35502592 | 2022 | Images from the Haematologica Atlas of Hematologic Cytology: acute myeloid leukemia with t(8;21)(q22;q22.1); RUNX1-RUNX1T1. | 1 |
| 37951201 | 2023 | Single-cell RNA-seq reveals novel immune-associated biomarkers for predicting prognosis in AML patients with RUNX1::RUNX1T1. | 0 |
| 39179670 | 2024 | STING is crucial for the survival of RUNX1::RUNX1T1 leukemia cells. | 0 |
| 39191510 | 2024 | WT1 together with RUNX1::RUNX1T1 targets DUSP6 to dampen ERK activity in acute myeloid leukaemia. | 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 |
| 30846508 | 2019 | More than a fusion gene: the RUNX1-RUNX1T1 AML. | 0 |
| 29872884 | 2018 | Myeloid neoplasms with t(16;21)(q24;q22)/RUNX1-RUNX1T3 mimics acute myeloid leukemia with RUNX1-RUNX1T1. | 0 |
| 31281149 | 2019 | [Genetic abnormalities in AML]. | 0 |
| 36653696 | 2023 | Comprehensive molecular understanding of pediatric acute myeloid leukemia. | 0 |
| 27770540 | 2017 | A minicircuitry of microRNA-9-1 and RUNX1-RUNX1T1 contributes to leukemogenesis in t(8;21) acute myeloid leukemia. | 0 |
| 39264725 | 2024 | Targeting Fatty Acid Metabolism Abrogates the Differentiation Blockade in Preleukemic Cells. | 0 |
| 19891700 | 2010 | Persistent altered fusion transcript splicing identifies RUNX1-RUNX1T1+ AML patients likely to relapse. | 0 |
| 24616160 | 2014 | Minimal residual disease monitoring in t(8;21) acute myeloid leukemia based on RUNX1-RUNX1T1 fusion quantification on genomic DNA. | 0 |
| 22032582 | 2011 | Core-binding factor acute myeloid leukemia. | 0 |
| 33782817 | 2021 | Relapsed RUNX1-RUNX1T1-positive acute myeloid leukemia with pseudo-Chediak-Higashi granules. | 0 |
| 17898786 | 2007 | Transcriptional dysregulation mediated by RUNX1-RUNX1T1 in normal human progenitor cells and in acute myeloid leukaemia. | 0 |
| 34014289 | 2021 | Coexistence of BCR-ABL1 and RUNX1-RUNX1T1 in a de novo AML. | 0 |
| 30919505 | 2019 | Measurable residual disease testing for personalized treatment of acute myeloid leukemia. | 0 |
| 38461410 | 2024 | Usefulness of KIT mutant transcript levels for monitoring measurable residual disease in t (8;21) acute myeloid leukemia. | 0 |
| 33524443 | 2021 | Optimized clinical application of minimal residual disease in acute myeloid leukemia with RUNX1-RUNX1T1. | 0 |
| 24327541 | 2014 | The role of topoisomerase II beta on breakage and proximity of RUNX1 to partner alleles RUNX1T1 and EVI1. | 0 |
| 35900542 | 2022 | Acute myeloid leukemia patients with variant or unusual translocations involving chromosomes 8 and 21 - A comprehensive cytogenetic profiling of three cases with review of literature. | 0 |
| 28322996 | 2017 | Assessing the miRNA sponge potential of RUNX1T1 in t(8;21) acute myeloid leukemia. | 0 |
| 21325813 | 2011 | Acute myeloid leukemia with a RUNX1-RUNX1T1 t(1;21;8)(q21;q22;q22) novel variant: a case report and review of the literature. | 0 |
| 26058961 | 2016 | MAPK8-mediated stabilization of SP1 is essential for RUNX1-RUNX1T1 - driven leukaemia. | 0 |
| 33067946 | 2020 | [Clinical Prognostic Factors Analysis of Initially Treated AML Children with t(8;21)/RUNX1-RUNX1T1()]. | 0 |
| 35152350 | 2022 | UBC9 inhibits myeloid differentiation in collaboration with AML1-MTG8. | 0 |
| 28299658 | 2017 | Clinical Relevance of RUNX1 and CBFB Alterations in Acute Myeloid Leukemia and Other Hematological Disorders. | 0 |
| 29472719 | 2018 | Epigenetic heterogeneity affects the risk of relapse in children with t(8;21)RUNX1-RUNX1T1-rearranged AML. | 0 |
| 39864466 | 2025 | Acute myeloid leukemia with t(8;21) translocation: Molecular pathogenesis, potential therapeutics and future directions. | 0 |
| 30569130 | 2019 | Disruption of MAPK1 expression in the ERK signalling pathway and the RUNX1‑RUNX1T1 fusion gene attenuate the differentiation and proliferation and induces the growth arrest in t(8;21) leukaemia cells. | 0 |
| 25348871 | 2015 | Prognosis and monitoring of core-binding factor acute myeloid leukemia: current and emerging factors. | 0 |
| 25635758 | 2015 | Emerging diagnostic and therapeutic approaches in core binding factor acute myeloid leukaemia. | 0 |
| 26320575 | 2015 | Decoding of exon splicing patterns in the human RUNX1-RUNX1T1 fusion gene. | 0 |
| 37024571 | 2023 | Avapritinib is effective for treatment of minimal residual disease in acute myeloid leukemia with t (8;21) and kit mutation failing to immunotherapy after allogeneic hematopoietic stem cell transplantation. | 0 |
| 38014874 | 2024 | KIT exon 17 mutations are predictive of inferior outcome in pediatric acute myeloid leukemia with RUNX1::RUNX1T1. | 0 |
| 39971668 | 2025 | The Prospective Use of Avapritinib in Relapsed/Refractory (R/R) RUNX1-RUNX1T1-Positive AML Patients With KIT Mutation. | 0 |
| 37102302 | 2023 | TP53 and RB1 alterations characterize poor prognostic subgroups in pediatric acute myeloid leukemia. | 0 |
| 29393574 | 2018 | Rare BCR-ABL1 transcript in a RUNX1-RUNX1T1-positive de novo acute myeloid leukemia: The chicken and egg tale. | 0 |
| 29264741 | 2018 | Rearrangement of VPS13B, a causative gene of Cohen syndrome, in a case of RUNX1-RUNX1T1 leukemia with t(8;12;21). | 0 |
| 38469780 | 2024 | AML with RUNX1::RUNX1T1 Cooperating two Mutations Relapsed Quickly after Achieving CR. | 0 |
| 38654658 | 2024 | Lower relapse incidence with haploidentical versus matched sibling or unrelated donor hematopoietic cell transplantation for core-binding factor AML patients in CR2: A study from the Global Committee and the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. | 0 |
Bibliography
No bibliography items were found for this article.
Summary
Fusion gene
RUNX1/RUNX1T1
t(8;21)(q22;q22) G- banding (left) - Courtesy Jean-Luc Lai and Alain Vanderhaegen (top) and Diane H. Norback, Eric B. Johnson, Sara Morrison-Delap http://www.slh.wisc.edu/cytogenetics (middle and below); R- banding (middle) - above: Jean Loup Huret; 2nd row: - Courtesy Christiane Charrin; 3rd and 4th row: - Courtesy Roland Berger. Right: FISH - Courtesy Hossein Mossafa.
Citation
Wilma Kroes ; Wilma Kroes
t(8;21)(q22;q22) RUNX1/RUNX1T1
Atlas Genet Cytogenet Oncol Haematol. 2016-05-01
Online version: http://atlasgeneticsoncology.org/haematological/1019/t(8;21)(q22;q22)-runx1-runx1t1
Historical Card
1997-09-01 t(8;21)(q22;q22) RUNX1/RUNX1T1 by Jean-Loup Huret,Jean-Loup Huret Affiliation
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France
