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t(20;21)(q13.2;q22.12) ZFP64::RUNX1

Written2012-12Nathalie Douet-Guilbert, Etienne De Braekeleer, Audrey Basinko, Marie-Josée Le Bris, Frédéric Morel, Marc De Braekeleer
Cytogenetics Laboratory, Faculty of Medicine, University of Brest, France

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ICD-Morpho 9989/3 Myelodysplastic syndrome, unclassifiable
Atlas_Id 1590

Clinics and Pathology

Disease Chronic myelomonocytic leukemia (CMML)
Epidemiology This is a rare chromosomal rearrangement, only reported twice in myeloid hemopathies, without molecular characterization but for the case reported by Richkind et al. (2000) who showed rearrangement of RUNX1 (Secker-Walker et al., 1995; Richkind et al., 2000).
Clinics A 91-year old woman seen for fever and thrombopenia.


Note The t(20;21)(q13.2;q22.12) involves the RUNX1 (alias AML1) gene that acts as an activator or repressor of target gene expression depending upon the large number of transcription factors, coactivators and corepressors that interact with it. RUNX1 functions as an organizing protein that facilitates assembly of transcriptional activation or repression complexes. All the translocations that retain Runt homology domain but remove the transcription activation domain have a leukemogenic effect by acting as dominant negative inhibitors of wild-type RUNX1 in transcription activation (De Braekeleer et al., 2011).
Cytogenetics Morphological t(20;21)(q13.2;q22.12) identified by FISH in a clone having a trisomy 8 (cryptic rearrangement).
  RHG banding showing chromosomes 20 and 21 and the derivatives der(20) and der(21).
Cytogenetics Molecular FISH showed that the breakpoint on 21q22 was located in RUNX1. To confirm the position of the breakpoint on chromosome 20, BACs located at 20q13 were used as probes in FISH experiments. Analysis with RP11-184L6 showed that one signal hybridized to the normal chromosome 20, and the other splitted and hybridized to both der(20) and der(21). Co-hybridization with the RP11-184L6 clone and a RUNX1 probe (RP11-77G18) showed two fusion signals. RP11-184L6 contains the ZFP64 gene.
  FISH with BACs RP11-77G18 (spectrum green, located in 21q22.12 and containing RUNX1) and RP11-184L6 (spectrum orange, located in 20q13.2 and containing ZFP64) showing co-hybridization of both derivative chromosomes.

Genes involved and Proteins

Gene NameRUNX1 (runt-related transcription factor 1 (acute myeloid leukemia 1; aml1 oncogene))
Location 21q22.12
Note RUNX1 belongs to a family of genes that share a 128 amino acid region of high sequence homology, known as the 'Runt domain', first identified in the Drosophila runt gene. This 'Runt homology domain' is responsible for heterodimerization with the core-binding factor-b (CBF-b or PEBP2b) to form a transcription factor and for DNA binding. RUNX1 acts as a key regulator of hematopoiesis through the regulation of various hematopoietic genes, including growth factors (GM-CSF, MPO and IL-3), surface receptors (TCRA, TCRB, M-CSF receptor and FLT3), signaling molecules (CDKN1A, BLK and BCL2) and transcription activators (STAT3 and MYB).
Dna / Rna The RUNX1 gene spans 260 kb and consists of 12 exons with two distinct promoters. At least 12 different RUNX1 mRNAs differing in their types of 5' and 3' untranslated regions (UTRs) and their coding regions are generated.
Protein The RUNX1 protein contains a 'Runt homology domain' as well as transcription activation and inhibition domains. It acts as an activator or repressor of target gene expression depending upon the large number of transcription factors, coactivators and corepressors that interact with it. RUNX1 functions as an organizing protein that facilitates assembly of transcriptional activation or repression complexes. By recruitment of non-DNA binding proteins as p300/CBP and histone acetyltransferase, it contributes to the activation of transcription of target genes. Upon recruitment of non-DNA binding repressors such as mSin3A, Groucho/TLE and histone deacetylase, it represses transcription of target genes.
Gene NameZFP64 (ZFP64 zinc finger protein)
Location 20q13.2
Dna / Rna The ZFP64 gene contains 6 exons spanning 41 kb. Twelwe transcripts are known, of which 9 are protein coding.
Protein ZFP64 protein belongs to the krueppel C2H2-type zinc-finger protein family and contains 9 C2H2-type zinc fingers. It may be involved in transcriptional regulation. It interacts with the intracellular domain of Notch1, and acts as a coactivator of the Notch intracellular domain (Sakamoto et al., 2008).

To be noted

Additional cases are needed to delineate the epidemiology of this rare entity:
you are welcome to submit a paper to our new Case Report section.


RUNX1 translocations and fusion genes in malignant hemopathies.
De Braekeleer E, Douet-Guilbert N, Morel F, Le Bris MJ, Ferec C, De Braekeleer M.
Future Oncol. 2011 Jan;7(1):77-91. doi: 10.2217/fon.10.158. (REVIEW)
PMID 21174539
Identification of two new translocations that disrupt the AML1 gene.
Richkind K, Hromas R, Lytle C, Crenshaw D, Velasco J, Roherty S, Srinivasiah J, Varella-Garcia M.
Cancer Genet Cytogenet. 2000 Oct 15;122(2):141-3. (REVIEW)
PMID 11106827
Zfp64 participates in Notch signaling and regulates differentiation in mesenchymal cells.
Sakamoto K, Tamamura Y, Katsube K, Yamaguchi A.
J Cell Sci. 2008 May 15;121(Pt 10):1613-23. doi: 10.1242/jcs.023119. Epub 2008 Apr 22.
PMID 18430783
Abnormalities of 3q21 and 3q26 in myeloid malignancy: a United Kingdom Cancer Cytogenetic Group study.
Secker-Walker LM, Mehta A, Bain B.
Br J Haematol. 1995 Oct;91(2):490-501.
PMID 8547101


This paper should be referenced as such :
Douet-Guilbert, N ; De, Braekeleer E ; Basinko, A ; Le, Bris MJ ; Morel, F ; De, Braekeleer M
t(20;21)(q13.2;q22.12) ZFP64/RUNX1
Atlas Genet Cytogenet Oncol Haematol. 2013;17(5):341-343.
Free journal version : [ pdf ]   [ DOI ]
On line version :

Translocations implicated (Data extracted from papers in the Atlas)

 t(20;21)(q13.2;q22.12) ZFP64/RUNX1

External links

Mitelman databaset(20;21)(q13.2;q22.12)
arrayMap (UZH-SIB Zurich)Topo ( C42) Morph ( 9989/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed
All articlesautomatic search in PubMed

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