Atlas of Genetics and Cytogenetics in Oncology and Haematology

Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

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

Written2016-05Wilma Kroes, Marian Stevens-Kroef
Department of Clinical Genetics, Leiden University Medical Center, Leiden; Department of Human Genetics, Radboud university medical center, Nijmegen, The Netherlands.;
This article is an update of :
1997-09Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

(Note : for Links provided by Atlas : click)


ICD-Morpho 9896/3 AML with t(8;21)(q22;q22); RUNX1-RUNX1T1
ICD-Morpho 9920/3 Therapy-related myeloid neoplasms
Atlas_Id 1019
  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 (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.

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 / cell stem 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.
Cytology See figure and legend.
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.
Prognosis Complete remission (CR) in most cases (90%) with relatively long disease-free survival when treated with high dose chemotherapy.


  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 NameRUNX1T1 (runt-related transcription factor 1; translocated to, 1 (cyclin D-related))
Location 8q21.3
Dna / Rna Transcription is from telomere to centromere.
Protein 3 proline rich domains, 2 Zn fingers, and in C-term, a PEST region; tissue restricted expression; nuclear localisation; putative transcription factor.
Gene NameRUNX1 (runt-related transcription factor 1 (acute myeloid leukemia 1; aml1 oncogene))
Location 21q22.12
Dna / Rna Transcription is from telomere to centromere.
Protein 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

Hybrid gene
  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 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
Fusion Protein
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.


Acute myelogenous leukemia with an 8;21 translocation. A report on 148 cases from the Groupe Français de Cytogénétique Hématologique (GFCH).
Cancer genetics and cytogenetics. 1990 ; 44 (2) : 169-179.
PMID 2297675
Cytologic characterization and significance of normal karyotypes in t(8;21) acute myeloblastic leukemia.
Berger R, Bernheim A, Daniel MT, Valensi F, Sigaux F, Flandrin G
Blood. 1982 ; 59 (1) : 171-178.
PMID 6947830
Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet
Döhner H, Estey EH, Amadori S, Appelbaum FR, Büchner T, Burnett AK, Dombret H, Fenaux P, Grimwade D, Larson RA, Lo-Coco F, Naoe T, Niederwieser D, Ossenkoppele GJ, Sanz MA, Sierra J, Tallman MS, Löwenberg B, Bloomfield CD; European LeukemiaNet.
Blood. 2010 Jan 21;115(3):453-74.
PMID 19880497
The 8;21 chromosome translocation in acute myeloid leukemia is always detectable by molecular analysis using AML1.
Maseki N, Miyoshi H, Shimizu K, Homma C, Ohki M, Sakurai M, Kaneko Y
Blood. 1993 ; 81 (6) : 1573-1579.
PMID 8453103
AML1 and the 8;21 and 3;21 translocations in acute and chronic myeloid leukemia.
Nucifora G, Rowley JD
Blood. 1995 ; 86 (1) : 1-14.
PMID 7795214
Molecular basis of the t(8;21) translocation in acute myeloid leukaemia.
Ohki M
Seminars in cancer biology. 1993 ; 4 (6) : 369-375.
PMID 8142622
WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues.
Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW.
4th Edition; Lyon, France: IARC Press; 2008.


This paper should be referenced as such :
Wilma Kroes, Marian Stevens-Kroef
t(8;21)(q22;q22) RUNX1/RUNX1T1
Atlas Genet Cytogenet Oncol Haematol. 2017;21(2):52-55.
Free journal version : [ pdf ]   [ DOI ]
On line version :
History of this paper:
Huret, JL. t(8;21)(q22;q22). Atlas Genet Cytogenet Oncol Haematol. 1997;1(1):23-25.

Other genes implicated (Data extracted from papers in the Atlas) [ 13 ]


Translocations implicated (Data extracted from papers in the Atlas)

 t(8;21)(q22;q22) RUNX1/RUNX1T1

External links

Mitelman databaset(8;21)(q22;q22)
COSMICHisto = - Site = haematopoietic_and_lymphoid_tissue (COSMIC)
arrayMap (UZH-SIB Zurich)Topo ( C42) Morph ( 9896/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMap (UZH-SIB Zurich)Topo ( C42) Morph ( 9920/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
Other databaseETO/AML1 translocation (8/21) (Bari)
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed
All articlesautomatic search in PubMed

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Mon Sep 7 15:07:54 CEST 2020

Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

For comments and suggestions or contributions, please contact us