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RUNX1 (runt-related transcription factor 1 (acute myeloid leukemia 1; aml1 oncogene))

Written2003-01Jean-Loup Huret, Sylvie Senon
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France
This article is an update of :
1997-12Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France
1997-11Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

(Note : for Links provided by Atlas : click)


Alias (NCBI)AML1 (acute myeloid leukemia 1)
CBFA2 (core binding factor A2)
PEBPaB (polyomavirus enhancer binding protein aB)
HGNC Alias symbPEBP2A2
HGNC Alias nameaml1 oncogene
HGNC Previous nameAML1
HGNC Previous nameacute myeloid leukemia 1
 runt-related transcription factor 1
 runt related transcription factor 1
LocusID (NCBI) 861
Atlas_Id 52
Location 21q22.12  [Link to chromosome band 21q22]
Location_base_pair Starts at 34787801 and ends at 35049298 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping RUNX1.png]
  AML1 (21q22.3) in normal cells: clone dJ1107L6 - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.
  RUNX1 (runt-related transcription factor 1 (acute myeloid leukemia 1; aml1 oncogene) Hybridization with SureFISH RUNX1 break apart probe (Agilent Technologies, Australia) showing the RUNX1 gene on 21q22.12 (red-green or a fused yellow signal) - Courtesy Adriana Zamecnikova.
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
ACKR2 (3p22.1) / RUNX1 (21q22.12)AFF3 (2q11.2) / RUNX1 (21q22.12)AKAP9 (7q21.2) / RUNX1 (21q22.12)
BRINP3 (1q31.1) / RUNX1 (21q22)CBFA2T3 (16q24.3) / RUNX1 (21q22.12)CHD1 (5q15) / RUNX1 (21q22.12)
DGKG (3q27.2) / RUNX1 (21q22.12)DPP10 (2q14.1) / RUNX1 (21q22.12)DYRK1A (21q22.13) / RUNX1 (21q22.12)
ETV6 (12p13.2) / RUNX1 (21q22.12)FBXO42 (1p36.13) / RUNX1 (21q22.12)FGA (4q31.3) / RUNX1 (21q22.12)
FUS (16p11.2) / RUNX1 (21q22.12)GSN (9q33.2) / RUNX1 (21q22.12)IFNGR2 (21q22.11) / RUNX1 (21q22.12)
LPXN (11q12.1) / RUNX1 (21q22.12)MACROD1 (11q13.1) / RUNX1 (21q22.12)MECOM (3q26.2) / RUNX1 (21q22.12)
NDST2 (10q22.2) / RUNX1 (21q22.12)PRDX4 (Xp22.11) / RUNX1 (21q22.12)RCAN1 (21q22.12) / RUNX1 (21q22.12)
RPL22 (1p36.31) / RUNX1 (21q22.12)RUNX1 (21q22.12) / ADAMTS19 (5q23.3)RUNX1 (21q22.12) / AFF3 (2q11.2)
RUNX1 (21q22.12) / BMPR1B (4q22.3)RUNX1 (21q22.12) / CBFA2T2 (20q11.21)RUNX1 (21q22.12) / CBFA2T3 (16q24.3)
RUNX1 (21q22.12) / CDR1 (Xq27.1)RUNX1 (21q22.12) / CEP76 (18p11.21)RUNX1 (21q22.12) / CLCA2 (1p22.3)
RUNX1 (21q22.12) / CPNE8 (12q12)RUNX1 (21q22.12) / DDX47 (12p13.1)RUNX1 (21q22.12) / DSCAM (21q22.2)
RUNX1 (21q22.12) / DYRK1A (21q22.13)RUNX1 (21q22.12) / ETV6 (12p13.2)RUNX1 (21q22.12) / EVX1 (7p15.2)
RUNX1 (21q22.12) / FAM117A (17q21.33)RUNX1 (21q22.12) / FBXW7 (4q31.3)RUNX1 (21q22.12) / GRM7 (3p26.1)
RUNX1 (21q22.12) / KCNMA1 (10q22.3)RUNX1 (21q22.12) / KIAA1549L (11p13)RUNX1 (21q22.12) / KRR1 (12q21.2)
RUNX1 (21q22.12) / LDLRAD4 (18p11.21)RUNX1 (21q22.12) / LIPA (10q23.31)RUNX1 (21q22.12) / LPXN (11q12.1)
RUNX1 (21q22.12) / MACROD1 (11q13.1)RUNX1 (21q22.12) / MECOM (3q26.2)RUNX1 (21q22.12) / MLYCD (16q23.3)
RUNX1 (21q22.12) / NDC1 (1p32.3)RUNX1 (21q22.12) / NLGN4Y (Yq11.221)RUNX1 (21q22.12) / NLRP2 (19q13.42)
RUNX1 (21q22.12) / NLRP4 (19q13.43)RUNX1 (21q22.12) / NOL4L (20q11.21)RUNX1 (21q22.12) / PDZD7 (10q24.31)
RUNX1 (21q22.12) / PRDM16 (1p36.32)RUNX1 (21q22.12) / PRDX4 (Xp22.11)RUNX1 (21q22.12) / PRRC1 (5q23.2)
RUNX1 (21q22.12) / PTHLH (12p11.22)RUNX1 (21q22.12) / RPL22 (1p36.31)RUNX1 (21q22.12) / RUNX1 (21q22.12)
RUNX1 (21q22.12) / RUNX1T1 (8q21.3)RUNX1 (21q22.12) / SH3D19 (4q31.3)RUNX1 (21q22.12) / SIN3A (15q24.2)
RUNX1 (21q22.12) / SNX29P2 (16p11.2)RUNX1 (21q22.12) / SUMO2P13 (6p22.3)RUNX1 (21q22.12) / SV2B (15q26.1)
RUNX1 (21q22.12) / TARDBP (1p36.22)RUNX1 (21q22.12) / TCF12 (15q21.3)RUNX1 (21q22.12) / TRPS1 (8q23.3)
RUNX1 (21q22.12) / TSPEAR (21q22.3)RUNX1 (21q22.12) / UBL7 (15q24.1)RUNX1 (21q22.12) / UGGT2 (13q32.1)
RUNX1 (21q22.12) / USP25 (21q21.1)RUNX1 (21q22.12) / USP42 (7p22.1)RUNX1 (21q22.12) / VAV1 (19p13.3)
RUNX1 (21q22.12) / YTHDF2 (1p35.3)RUNX1 (21q22.12) / ZADH2 (18q22.3)RUNX1 (21q22.12) / ZFPM2 (8q23.1)
RUNX1 (21q22.12) / ZNF687 (1q21.3)RUNX1T1 (8q21.3) / RUNX1 (21q22.12)TVP23C (17p12) / RUNX1 (21q22)
USP16 (21q21.3) / RUNX1 (21q22.12)USP42 (7p22.1) / RUNX1 (21q22.12)YTHDF2 (1p35.3) / RUNX1 (21q22.12)
ZNF687 (1q21.3) / RUNX1 (21q22.12)


  DNA Diagram
Description the gene spans a region of more than 120 kb
Transcription transcription is from telomere to centromere --> the fusion gene is located on the 'other' chromosome (eg the der(8) of the t(8;21), the der(3) of the t(3;21)...); alternate splicing --> transcripts of 2, 3.3, ->7.5 and 8 kb


  Protein Diagram
Description 250, 453 amino acids and other forms; forms heterodimers with CBFB
Expression widely expressed, including hematopoietic cells at various stages of differenciation: role in haematopoiesis
Localisation nuclear
Function transcription factor (activator) for various hematopoietic-specific genes: binds to the core site 5' PyGPyGGTPy 3' of a number of promotors and enhancers, as in GM-CSF (granulocyte-macrophage colony stimulating factor), CSF1R (colony stimulating factor 1 receptor), TCRb sites (T cell antigen receptors), and myeloid myeloperoxidase
Homology 1- Runt (drosophila): nuclear DNA binding protein; role in segmentation (embryology); 2- AML2 (also called: CBFA3, CBFa3, PEBPaC), located in 1p35-36, expressed in B lineage (3 and 5 kb RNA); AML3: (also called: CBFA1, CBFa1, PEBPaA) in 6p21; 3- cbfa family (mouse)

Implicated in

Entity Familial platelet disorder with predisposition to acute non lymphocytic leukemia
Entity t(1;21)(p36;q22) treatment related acute non lymphocytic leukemia (AML) --> ?/ RUNX1
Entity t(2;21)(p11;q22) AML --> ?/ RUNX1
Entity t(3;21)(q26;q22)/ myelodysplastic syndrome (MDS) or AML --> EVI1 or EAP/ MDS1 - RUNX1
Disease CML-BC of myeloid type; AML and MDS, often therapy related (secondary to antitopoisomerase II)
Hybrid/Mutated Gene 5' AML1 - 3' EAP or MDS1 or EVI1
Entity t(4;21)(q31;q22) T-cell acute lymphoblastic leukemia (T-ALL) --> ?/ RUNX1
Entity t(5;21)(q13;q22) myelodysplastic syndrome (MDS) and AML --> ?/ RUNX1
Entity t(8;21)(q22;q22)/AML. --> ETO - RUNX1
Disease AML, M2 mostly
Prognosis CR is obtained; median survival (1.5-2 yrs) is the range with other AML or relatively better
Cytogenetics additional anomalies are frequent: loss of Y or X chromosome, del(7q)/-7, +8, del (9q); complex t(8;21;Var) are known and have revealed that the crucial event lies on der(8); in agrement with the fact that both genes are transcribed from telomere to centromere
Hybrid/Mutated Gene 5' AML1 - 3' ETO
Abnormal Protein N-term AML1 with the Runt domain fused to the nearly entire ETO
Oncogenesis the fusion protein retain the ability to recognize the AML1 concensus binding site (--> negative dominant competitor with the normal AML1) and to dimerize with the cbtb/CBTB subunit --> probable altered transcriptional regulation of normal AML1 target genes
Entity t(8;21)(q23;q22) MDS --> FOG2 / RUNX1
Entity t(8;21)(q24;q22) ALL and AML --> TRPS1 / RUNX1
Entity t(12;21)(p13;q22)/ALL --> ETV6- RUNX1
Disease B cell ALL (CD10+)
Prognosis CR in all cases; prognosis seems good
Cytogenetics often undetectable without FISH; additional anomalies: frequent del(12)(p12) on the other allele
Hybrid/Mutated Gene 5' ETV6 - 3' AML1on the der(21)
Abnormal Protein Helix loop helix of TEL fused to the nearly entire AML1 protein; the other TEL allele is often deleted
Entity t(12;21)(q24;q22) AML --> ?/ RUNX1
Entity t(16;21)(q24;q22) AML --> MTG16- RUNX1
Disease AML and therapy related AML; mainly with preceeding MDS
Prognosis very poor
Entity t(17;21)(q11;q22) RUNX1
Entity t(19;21)(q13;q22) treatment related AML --> AMP19 / RUNX1
Entity t(20;21)(q1;3q22) treatment related ANL --> ? / RUNX1
Entity t(21;21)(q11;q22) MDS --> UPS25 / RUNX1




AML1-TRPS1 chimeric protein is generated by t(8;21)(q24;q22) in relapsing acute myeloblastic leukemia.
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A novel CBFA2 single-nucleotide mutation in familial platelet disorder with propensity to develop myeloid malignancies.
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Blood. 2001 ; 98 (9) : 2856-2858.
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A novel syndrome of radiation-associated acute myeloid leukemia involving AML1 gene translocations.
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Blood. 2000 ; 95 (12) : 4011-4013.
PMID 10845943
Combined spectral karyotyping and DAPI banding analysis of chromosome abnormalities in myelodysplastic syndrome.
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PMID 10534769
Concurrent translocations of MLL and CBFA2 (AML1) genes with new partner breakpoints in a child with secondary myelodysplastic syndrome after treatment of acute lymphoblastic leukemia.
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Genes, chromosomes & cancer. 2000 ; 28 (2) : 227-232.
PMID 10825008
Novel cryptic, complex rearrangements involving ETV6-CBFA2 (TEL-AML1) genes identified by fluorescence in situ hybridization in pediatric patients with acute lymphoblastic leukemia.
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PMID 11550288
In vitro analyses of known and novel RUNX1/AML1 mutations in dominant familial platelet disorder with predisposition to acute myelogenous leukemia: implications for mechanisms of pathogenesis.
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Blood. 2002 ; 99 (4) : 1364-1372.
PMID 11830488
A new translocation that rearranges the AML1 gene in a patient with T-cell acute lymphoblastic leukemia.
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Cancer genetics and cytogenetics. 2002 ; 135 (1) : 96-100.
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Blood. 1995 ; 86 (1) : 1-14.
PMID 7795214
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Seminars in cancer biology. 1993 ; 4 (6) : 369-375.
PMID 8142622
Identification of two new translocations that disrupt the AML1 gene.
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High frequency of t(12;21) in childhood B-lineage acute lymphoblastic leukemia.
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PMID 7492786
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PMID 9763573
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This paper should be referenced as such :
Huret, JL ; Senon, S
AML1 (acute myeloid leukemia 1) - RUNX1 (runt-related transcription factor 1 (acute myeloid leukemia 1; aml1 oncogene)) - CBFA2 (core binding factor A2)
Atlas Genet Cytogenet Oncol Haematol. 2003;7(2):84-87.
Free journal version : [ pdf ]   [ DOI ]
History of this paper:
Huret, JL. AML1 (acute myeloid leukemia 1). Atlas Genet Cytogenet Oncol Haematol. 1997;1(2):59-61.
Huret, JL ; Senon, S. AML1 (acute myeloid leukemia 1) - RUNX1 (runt-related transcription factor 1 (acute myeloid leukemia 1; aml1 oncogene)) - CBFA2 (core binding factor A2). Atlas Genet Cytogenet Oncol Haematol. 2003;7(2):84-87.

Other Leukemias implicated (Data extracted from papers in the Atlas) [ 105 ]
  21q22 rearrangements (RUNX1) in treatment related leukemia
3q26 rearrangements (MECOM) in myeloid malignancies
Acute myeloid leukemia with myelodysplasia related changes
Classification of acute myeloid leukemias
Classification of myelodysplastic syndromes 2015
Chronic Myelomonocytic Leukemia (CMML)
del(21)(q21q22) USP16/RUNX1
del(9p) in Acute Lymphoblastic Leukemia
dic(9;20)(p11-13;q11) PAX5/Various
dup(21q) amplified (RUNX1)
Early T-cell precursor acute lymphoblastic leukemia
i(Xq10) in female patients
Mixed phenotype acute leukemia (MPAL)
Myelodysplastic/myeloproliferative neoplasms
Myelodysplastic syndrome with excess blasts
Myeloid sarcoma
Pediatric T-Cell Acute Lymphoblastic Leukemia
t(1;1)(p36;p36) PRDM16/SKI
t(1;2)(p36;p21) THADA/PRDM16
t(1;7)(p36;p12) IKZF1/PRDM16
t(1;9)(p13;p12) PAX5/HIPK1
t(1;21)(p36;q22) RUNX1/PRDM16
t(1;21)(p22;q22) RUNX1/CLCA2
t(1;21)(p32;q22) RUNX1/?
t(1;21)(p35;q22) RUNX1/YTHDF2
der(21)t(1;21)(q11-12;p11-13) and der(21)t(1;21)(q21-32;p11-13)
t(1;21)(q12;q22) RUNX1/?
t(1;21)(q21;q22) RUNX1/ZNF687
t(2;8)(p23;p11) KAT6A/ASXL2
t(2;21)(p11;q22) RUNX1/?
t(3;7)(q26;q21) MECOM/CDK6
t(3;21)(q26;q22) RUNX1/MECOM
t(3;21)(p12;q22) RUNX1/?
t(3;21)(q26;q22) RUNX1/MECOM in treatment related leukemia
t(4;11)(q21;q23) KMT2A/AFF1
t(4;11)(p12;q23) KMT2A/FRYL
t(4;21)(q31;q22) RUNX1/?
t(4;21)(q31;q22) RUNX1/SH3D19
t(4;21)(q35;q22) RUNX1/?
t(5;7)(q35;q21) TLX3/CDK6
t(5;21)(q13;q22) RUNX1/?
t(6;21)(p22;q22) RUNX1-?
t(7;21)(p15;q22) RUNX1/?
t(7;21)(p22;q22) RUNX1/USP42
t(8;21)(q22;q22) RUNX1/RUNX1T1
t(8;21)(q22;q22) RUNX1/RUNX1T1 in treatment related leukemia
t(8;21)(q23;q22) RUNX1/ZFPM2
t(8;21)(q24;q22) RUNX1/TRPS1
t(9;21)(q34;q22) RUNX1 truncated
t(X;21)(p11;q22) RUNX1/?
t(X;21)(q26;q22) ELF4/ERG
t(11;12)(p15;q13) NUP98/HOXC11::t(11;12)(p15;q13) NUP98/HOXC13
t(11;21)(p14;q22) RUNX1/KIAA1549L
t(11;21)(q13;q22) RUNX1/MACROD1
t(11;21)(q21;q22) RUNX1/LPXN
t(12;21)(p13;q22) ETV6/RUNX1
t(12;21)(q12;q22) RUNX1 truncated
t(12;21)(q24;q22) RUNX1/?
t(14;19)(q32;p13) IGH/EPOR::t(14;19)(q32;p13) IGH/BRD4 ?
t(14;21)(q22;q22) RUNX1/?
t(15;21)(q22;q22) RUNX1/?
t(16;21)(q24;q22) RUNX1/CBFA2T3
t(17;21)(q11.2;q22) RUNX1/?
t(18;21)(q21;q22) RUNX1/?
t(19;21)(q13.4;q22) RUNX1 truncated
t(20;21)(q11;q22) RUNX1/NOL4L
t(20;21)(q13;q22) RUNX1/?
t(20;21)(q13.2;q22.12) ZFP64/RUNX1
TAL1 (1p32) deletion in lymphoid malignancies
Therapy-Related Hematopoietic Neoplasia
ins(21;20)(q22;q11q11) RUNX1/CBFA2T2
t(1;21)(p32;q22) RUNX1/NDC1
t(2;21)(q11;q22) RUNX1/AFF3
t(3;21)(q26;q22) RUNX1/RPL22P1
t(5;21)(q21;q22) CHD1/RUNX1
t(5;21)(q23;q22) RUNX1/ADAMTS19
t(5;21)(q23;q22) RUNX1/PRRC1
t(6;21)(p22;q22) RUNX1/SUMO2P13
t(7;21)(p15;q22) RUNX1/EVX1
t(10;21)(q22;q22) NDST2/RUNX1
t(10;21)(q22;q22) RUNX1/KCNMA1
t(10;21)(q23;q22) RUNX1/LIPA
t(10;21)(q24;q22) RUNX1/PDZD7
t(12;21)(p11;q22) RUNX1/PTHLH
t(12;21)(p13;q22) RUNX1/DDX47
t(12;21)(q12;q22) RUNX1/CPNE8
t(12;21)(q21;q22) RUNX1/KRR1
t(13;21)(q32;q22) RUNX1/UGGT2
t(15;21)(q21;q22) RUNX1/TCF12
t(15;21)(q24;q22) RUNX1/SIN3A
t(15;21)(q24;q22) RUNX1/UBL7
t(15;21)(q26;q22) RUNX1/SV2B
t(16;21)(q23;q22) RUNX1/MLYCD
t(17;21)(q21;q22) RUNX1/FAM117A
t(18;21)(q22;q22) RUNX1/ZADH2
t(21;21)(q22;q22) RUNX1/DSCAM
t(21;21)(q22;q22) RUNX1/DYRK1A
+13 or trisomy 13
+16 or trisomy 16 (solely)
+21 or trisomy 21
t(X;21)(p22;q22) RUNX1/PRDX4

Other Cancer prone implicated (Data extracted from papers in the Atlas) [ 2 ]
  Familial Myeloproliferative Disorders Familial platelet disorder with predisposition to acute myelogenous leukemia

External links

HGNC (Hugo)RUNX1   10471
LRG (Locus Reference Genomic)LRG_482
Entrez_Gene (NCBI)RUNX1    RUNX family transcription factor 1
AliasesAML1; AML1-EVI-1; AMLCR1; CBF2alpha; 
CBFA2; EVI-1; PEBP2aB; PEBP2alpha
GeneCards (Weizmann)RUNX1
Ensembl hg19 (Hinxton)ENSG00000159216 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000159216 [Gene_View]  ENSG00000159216 [Sequence]  chr21:34787801-35049298 [Contig_View]  RUNX1 [Vega]
ICGC DataPortalENSG00000159216
TCGA cBioPortalRUNX1
Genatlas (Paris)RUNX1
SOURCE (Princeton)RUNX1
Genetics Home Reference (NIH)RUNX1
Genomic and cartography
GoldenPath hg38 (UCSC)RUNX1  -     chr21:34787801-35049298 -  21q22.12   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)RUNX1  -     21q22.12   [Description]    (hg19-Feb_2009)
GoldenPathRUNX1 - 21q22.12 [CytoView hg19]  RUNX1 - 21q22.12 [CytoView hg38]
genome Data Viewer NCBIRUNX1 [Mapview hg19]  
OMIM151385   601399   601626   
Gene and transcription
Genbank (Entrez)AA878154 AK226159 AK310587 AK310646 AL581043
RefSeq transcript (Entrez)NM_001001890 NM_001122607 NM_001754
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)RUNX1
Alternative Splicing GalleryENSG00000159216
Gene ExpressionRUNX1 [ NCBI-GEO ]   RUNX1 [ EBI - ARRAY_EXPRESS ]   RUNX1 [ SEEK ]   RUNX1 [ MEM ]
Gene Expression Viewer (FireBrowse)RUNX1 [ Firebrowse - Broad ]
GenevisibleExpression of RUNX1 in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)861
GTEX Portal (Tissue expression)RUNX1
Human Protein AtlasENSG00000159216-RUNX1 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Conserved Domain (NCBI)RUNX1
Blocks (Seattle)RUNX1
Human Protein Atlas [tissue]ENSG00000159216-RUNX1 [tissue]
IPIIPI00477787   IPI00218529   IPI00218530   IPI00218936   IPI00936936   IPI00797455   IPI00952824   IPI00939238   IPI00218943   IPI00941683   IPI00871743   IPI00218942   IPI01018795   IPI00816187   IPI00413370   IPI00791456   IPI00794722   
Protein Interaction databases
Ontologies - Pathways
PubMed499 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
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