t(8;21)(q22;q22) RUNX1/RUNX1T1

2016-05-01   Wilma Kroes , Wilma Kroes 

1.Department of Clinical Genetics, Leiden University Medical Center, Leiden; Department of Human Genetics, Radboud university medical center, Nijmegen, The Netherlands. w.g.m.kroes@lumc.nl; Marian.Stevens-Kroef@radboudumc.nl
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.
Atlas Image
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

Atlas Image
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

Atlas Image
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 IDYearTitleCitations
354455942022Comprehensive Mutation Profile in Acute Myeloid Leukemia Patients with RUNX1-RUNX1T1 or CBFB-MYH11 Fusions0
355025922022Images from the Haematologica Atlas of Hematologic Cytology: acute myeloid leukemia with t(8;21)(q22;q22.1); RUNX1-RUNX1T1.0
354550502022Lessons Learned from Donor Cell-Derived Myeloid Neoplasms: Report of Three Cases and Review of the Literature.0
348186922022The clinical characteristics and prognosis of Chinese acute myeloid leukemia patients with CSF3R mutations.0
353267052022CDK6 Degradation Is Counteracted by p16INK4A and p18INK4C in AML.1
347397012022Non-age-related neoplastic loss of sex chromosome correlated with prolonged survival in real-world CBF-AML patients.0
350081062022Genome-wide DNA methylation analysis in pediatric acute myeloid leukemia.0
350709772021Preemptive Immunotherapy for Minimal Residual Disease in Patients With t(8;21) Acute Myeloid Leukemia After Allogeneic Hematopoietic Stem Cell Transplantation.1
350656802022Targeting PARP proteins in acute leukemia: DNA damage response inhibition and therapeutic strategies.2
356626932022CNST is Characteristic of Leukemia Stem Cells and is Associated With Poor Prognosis in AML.0
351523502022UBC9 inhibits myeloid differentiation in collaboration with AML1-MTG8.0
349212232021Epigenetic silencing of UBXN8 contributes to leukemogenesis in t(8;21) acute myeloid leukemia.0
355630852022Mutated KIT Tyrosine Kinase as a Novel Molecular Target in Acute Myeloid Leukemia.0
341480542021RUNX1-ETO (RUNX1-RUNX1T1) induces myeloid leukemia in mice in an age-dependent manner.0
353816742022[Short-term efficacy of venetoclax combined with azacitidine in acute myeloid leukemia: a single-institution experience].0
351858992022Case Report: Preemptive Treatment With Low-Dose PD-1 Blockade and Azacitidine for Molecular Relapsed Acute Myeloid Leukemia With RUNX1-RUNX1T1 After Allogeneic Hematopoietic Stem Cell Transplantation.0
346383012021Impact of KMT2A Rearrangement and CSPG4 Expression in Pediatric Acute Myeloid Leukemia.1
341251732021Tumor suppressor function of Gata2 in acute promyelocytic leukemia.1
340821592021Comparable Outcomes After Alternative and Matched Sibling Donor Hematopoietic Stem Cell Transplantation and the Role of Molecular Measurable Residual Disease for Acute Myeloid Leukemia in Elderly Patients.2
352644982022[A favorable clinical course of acute myeloid leukemia with t (6;21;8)(p23;q22;q22)].0
350456702021[Analysis of risk factors of relapse after allogeneic hematopoietic stem cell transplantation in patients with t (8;21) acute myeloid leukemia].0
349450032021PARP Inhibitors and Myeloid Neoplasms: A Double-Edged Sword.1
346746152021Clinical values of gene alterations as marker of minimal residual disease in non-M3 acute myeloid leukemia.0
342724862021Prognostic value of measurable residual disease at allogeneic transplantation for adults with core binding factor acute myeloid leukemia in complete remission.0
330541282021Engineered type 1 regulatory T cells designed for clinical use kill primary pediatric acute myeloid leukemia cells.3
340206862021Complex rearrangement in acute myeloid leukemia M2 with RUNX1/RUNX1T1 fusion involving chromosomes 8, 17 and 21.0
334746292021Both the subtypes of KIT mutation and minimal residual disease are associated with prognosis in core binding factor acute myeloid leukemia: a retrospective clinical cohort study in single center.3
337734072021A new four-way complex translocation variant involving the t(8;5;21;4)(q21;q13,q22,q31) and the relocalization of AML1/ETO fusion gene.0
339280202021Characteristics of Cohesin Mutation in Acute Myeloid Leukemia and Its Clinical Significance.1
341203312021Droplet digital polymerase chain reaction assay for the detection of the minor clone of KIT D816V in paediatric acute myeloid leukaemia especially showing RUNX1-RUNX1T1 transcripts.0
339367332021An unusual case of chronic lymphocytic leukemia with trisomy 12 presenting with prolymphocytic transformation and t(8;21)(q22;q22).0
342006302021DNA Methylation Signatures Predict Cytogenetic Subtype and Outcome in Pediatric Acute Myeloid Leukemia (AML).0
336478132021A novel case of intrachromosomal amplification and insertion of RUNX1 on derivative chromosome 2 in pediatric AML.0
335310672021MicroRNA let-7b downregulates AML1-ETO oncogene expression in t(8;21) AML by targeting its 3'UTR.3
340949822021Measurable Residual Disease Detected by Multiparameter Flow Cytometry and Sequencing Improves Prediction of Relapse and Survival in Acute Myeloid Leukemia.0
340142892021Coexistence of BCR-ABL1 and RUNX1-RUNX1T1 in a de novo AML.0
337828172021Relapsed RUNX1-RUNX1T1-positive acute myeloid leukemia with pseudo-Chediak-Higashi granules.0
333867422021Salmon-coloured granules in residual acute myeloid leukaemia with t(8;21)(q22;q22.1); RUNX1-RUNX1T1.0
339736432021Clinicopathological Evaluation of Acute Leukemias in a Tertiary Care Hospital: A Cross-Sectional Study.0
334835062021RUNX1/RUNX1T1 mediates alternative splicing and reorganises the transcriptional landscape in leukemia.4
334775842021Prognostic Impacts of D816V KIT Mutation and Peri-Transplant RUNX1-RUNX1T1 MRD Monitoring on Acute Myeloid Leukemia with RUNX1-RUNX1T1.0
318966842021Measurable residual disease monitoring provides insufficient lead-time to prevent morphologic relapse in the majority of patients with core-binding factor acute myeloid leukemia.8
335244432021Optimized clinical application of minimal residual disease in acute myeloid leukemia with RUNX1-RUNX1T1.2
333037092020Changing the frequency and spectra of chromosomal aberrations in Korean patients with acute leukemia in a tertiary care hospital.0
338365812021Enhanced cytarabine-induced killing in OGG1-deficient acute myeloid leukemia cells.2
338161052021Primary peritoneal myeloid sarcoma in association with CBFB/MYH11 fusion.0
338037392021Induction of AML Preleukemic Fusion Genes in HSPCs and DNA Damage Response in Preleukemic Fusion Gene Positive Samples.1
337233382021Treatment outcomes of pediatric acute myeloid leukemia: a retrospective analysis from 1996 to 2019 in Taiwan.0
332087712020RNA sequencing as an alternative tool for detecting measurable residual disease in core-binding factor acute myeloid leukemia.2
332049992020Identification of Fusion Gene Breakpoints is Feasible and Facilitates Accurate Sensitive Minimal Residual Disease Monitoring on Genomic Level in Patients With PML-RARA, CBFB-MYH11, and RUNX1-RUNX1T1.0
332174772021The RUNX1/RUNX1T1 network: translating insights into therapeutic options.1
328039992021Characteristics and prognosis of pediatric myeloid sarcoma in the cytogenetic context of t(8;21).1
330679462020[Clinical Prognostic Factors Analysis of Initially Treated AML Children with t(8;21)/RUNX1-RUNX1T1].0
327576862020Machine learning derived genomics driven prognostication for acute myeloid leukemia with RUNX1-RUNX1T1.2
347661232020Modelling t(8;21) acute myeloid leukaemia - What have we learned?1
324600282020Expression of RUNX1-ETO Rapidly Alters the Chromatin Landscape and Growth of Early Human Myeloid Precursor Cells.6
321016402020Significance of minimal residual disease monitoring by real-time quantitative polymerase chain reaction in core binding factor acute myeloid leukemia for transplantation outcomes.3
321155722020ZBTB7A prevents RUNX1-RUNX1T1-dependent clonal expansion of human hematopoietic stem and progenitor cells.6
324193642020Clinical and immunological features of platelet transfusion refractoriness in young patients with de novo acute myeloid leukemia.1
321755992020Measurable residual disease assessment by qPCR in peripheral blood is an informative tool for disease surveillance in childhood acute myeloid leukaemia.3
323118902020[The prognostic value of cloned genetic mutations detected by second-generation sequencing in RUNX1-RUNX1T1 positive acute myeloid leukemia patients receiving intensive consolidation therapy].1
325398152020Allogeneic hematopoietic stem cell transplantation can improve the prognosis of high-risk pediatric t(8;21) acute myeloid leukemia in first remission based on MRD-guided treatment.5
318967822020The clinical mutatome of core binding factor leukemia.25
320212702020Urgent Chemotherapy Successfully Rescues a Near Death Patient of Acute Intracranial Hypertension Caused by Intracranial Myeloid Sarcoma.0
317567772020Detection of rare reciprocal RUNX1 rearrangements by next-generation sequencing in acute myeloid leukemia.4
316886182020Prognostic Role of Postinduction Minimal Residual Disease and Myeloid Sarcoma Type Extramedullary Involvement in Pediatric RUNX1-RUNX1T1 (+) Acute Myeloid Leukemia.2
318390362019[Related Factors Affecting Long-term Prognosis of AML Children with Positive RUNX1-RUNX1T1].0
318179112019Core Binding Factor Leukemia: Chromatin Remodeling Moves Towards Oncogenic Transcription.4
318564352019[An interlaboratory comparison study on the detection of RUNX1-RUNX1T1 fusion transcript levels and WT1 transcript levels].0
312476752019Negative CD19 expression is associated with inferior relapse-free survival in children with RUNX1-RUNX1T1-positive acute myeloid leukaemia: results from the Japanese Paediatric Leukaemia/Lymphoma Study Group AML-05 study.5
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320921392020Combination of dasatinib with chemotherapy in previously untreated core binding factor acute myeloid leukemia: CALGB 10801.13
317516752020Subgroup Analysis Can Optimize the Relapse-Prediction Cutoff Value for WT1 Expression After Allogeneic Hematologic Stem Cell Transplantation in Acute Myeloid Leukemia.2
317259542020Morphological characteristics, cytogenetic profile, and outcome of RUNX1-RUNX1T1-positive acute myeloid leukemia: Experience of an Indian tertiary care center.0
317754822019[Characteristic and prognostic significance of leukemia stem cells associated antigens expressions in t (8;21) acute myeloid leukemia].0
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318997992020Prospective evaluation of prognostic impact of KIT mutations on acute myeloid leukemia with RUNX1-RUNX1T1 and CBFB-MYH11.17
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Bibliography

No bibliography items were found for this article.

Summary

Fusion gene

RUNX1/RUNX1T1
Atlas Image
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 

Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France