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

2003-01-01   Jean-Loup Huret , Sylvie Senon 

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

Identity

HGNC
LOCATION
21q22.12
IMAGE
Atlas Image
LEGEND
AML1 (21q22.3) in normal cells: clone dJ1107L6 - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.
IMAGE
Atlas Image
LEGEND
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.
LOCUSID
ALIAS
AML1,AML1-EVI-1,AMLCR1,CBF2alpha,CBFA2,EVI-1,PEBP2aB,PEBP2alpha
FUSION GENES

DNA/RNA

Atlas Image
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

Proteins

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 name
Familial platelet disorder with predisposition to acute non lymphocytic leukemia
Disease
CML-BC of myeloid type; AML and MDS, often therapy related (secondary to antitopoisomerase II)
Hybrid gene
5 AML1 - 3 EAP or MDS1 or EVI1
Entity name
t(4;21)(q31;q22) T-cell acute lymphoblastic leukemia (T-ALL) --> ?/ 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 gene
5 AML1 - 3 ETO
Fusion 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 name
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 gene
5 ETV6 - 3 AML1on the der(21)
Fusion protein
Helix loop helix of TEL fused to the nearly entire AML1 protein; the other TEL allele is often deleted
Entity name
Disease
AML and therapy related AML; mainly with preceeding MDS
Prognosis
very poor

Bibliography

Pubmed IDLast YearTitleAuthors
116753612001A novel CBFA2 single-nucleotide mutation in familial platelet disorder with propensity to develop myeloid malignancies.Buijs A et al
105085021999A new angle on a pervasive oncogene.Cleary ML et al
108459432000A novel syndrome of radiation-associated acute myeloid leukemia involving AML1 gene translocations.Hromas R et al
105347691999Combined spectral karyotyping and DAPI banding analysis of chromosome abnormalities in myelodysplastic syndrome.Kakazu N et al
108250082000Concurrent translocations of MLL and CBFA2 (AML1) genes with new partner breakpoints in a child with secondary myelodysplastic syndrome after treatment of acute lymphoblastic leukemia.Mathew S et al
115502882001Novel cryptic, complex rearrangements involving ETV6-CBFA2 (TEL-AML1) genes identified by fluorescence in situ hybridization in pediatric patients with acute lymphoblastic leukemia.Mathew S et al
118304882002In 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.Michaud J et al
120722072002A new translocation that rearranges the AML1 gene in a patient with T-cell acute lymphoblastic leukemia.Mikhail FM et al
77952141995AML1 and the 8;21 and 3;21 translocations in acute and chronic myeloid leukemia.Nucifora G et al
81426221993Molecular basis of the t(8;21) translocation in acute myeloid leukaemia.Ohki M et al
111068272000Identification of two new translocations that disrupt the AML1 gene.Richkind K et al
74927861995High frequency of t(12;21) in childhood B-lineage acute lymphoblastic leukemia.Romana SP et al
97635731998CBFA2(AML1) translocations with novel partner chromosomes in myeloid leukemias: association with prior therapy.Roulston D et al

Other Information

Locus ID:

NCBI: 861
MIM: 151385
HGNC: 10471
Ensembl: ENSG00000159216

Variants:

dbSNP: 861
ClinVar: 861
TCGA: ENSG00000159216
COSMIC: RUNX1

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000159216ENST00000300305Q01196
ENSG00000159216ENST00000344691Q01196
ENSG00000159216ENST00000358356Q01196
ENSG00000159216ENST00000399237A8MZI9
ENSG00000159216ENST00000399240H9KVB1
ENSG00000159216ENST00000416754A0A0C4DG58
ENSG00000159216ENST00000437180Q01196
ENSG00000159216ENST00000455571C9JWM1
ENSG00000159216ENST00000475045V9GYT5
ENSG00000159216ENST00000482318V9GYT3

Expression (GTEx)

0
5
10
15
20
25
30
35

Pathways

PathwaySourceExternal ID
Tight junctionKEGGko04530
Chronic myeloid leukemiaKEGGko05220
Acute myeloid leukemiaKEGGko05221
Tight junctionKEGGhsa04530
Pathways in cancerKEGGhsa05200
Chronic myeloid leukemiaKEGGhsa05220
Acute myeloid leukemiaKEGGhsa05221
Transcriptional misregulation in cancerKEGGko05202
Transcriptional misregulation in cancerKEGGhsa05202
Transmembrane transport of small moleculesREACTOMER-HSA-382551
SLC-mediated transmembrane transportREACTOMER-HSA-425407
Transport of glucose and other sugars, bile salts and organic acids, metal ions and amine compoundsREACTOMER-HSA-425366
Organic cation/anion/zwitterion transportREACTOMER-HSA-549132
Organic cation transportREACTOMER-HSA-549127
Th17 cell differentiationKEGGko04659
Th17 cell differentiationKEGGhsa04659

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
173775322007Foxp3 controls regulatory T-cell function by interacting with AML1/Runx1.233
175894982007MicroRNAs 17-5p-20a-106a control monocytopoiesis through AML1 targeting and M-CSF receptor upregulation.166
179966492007Epigenetic silencing of the myelopoiesis regulator microRNA-223 by the AML1/ETO oncoprotein.130
215712182011Genome-wide analysis of simultaneous GATA1/2, RUNX1, FLI1, and SCL binding in megakaryocytes identifies hematopoietic regulators.116
182022912008Initiating and cancer-propagating cells in TEL-AML1-associated childhood leukemia.115
230281382012Impact of an exercise intervention on DNA methylation in skeletal muscle from first-degree relatives of patients with type 2 diabetes.113
125763322003RUNX1 and GATA-1 coexpression and cooperation in megakaryocytic differentiation.103
198086972009AML1/RUNX1 mutations in 470 adult patients with de novo acute myeloid leukemia: prognostic implication and interaction with other gene alterations.90
198086972009AML1/RUNX1 mutations in 470 adult patients with de novo acute myeloid leukemia: prognostic implication and interaction with other gene alterations.90
205477492010Genome-wide analysis of estrogen receptor alpha DNA binding and tethering mechanisms identifies Runx1 as a novel tethering factor in receptor-mediated transcriptional activation.87

Citation

Jean-Loup Huret ; Sylvie Senon

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

Atlas Genet Cytogenet Oncol Haematol. 2003-01-01

Online version: http://atlasgeneticsoncology.org/gene/52/aml1id52

Historical Card

1997-12-01 RUNX1 (runt-related transcription factor 1 (acute myeloid leukemia 1; aml1 oncogene)) by  Jean-Loup Huret 

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

1997-11-01 RUNX1 (runt-related transcription factor 1 (acute myeloid leukemia 1; aml1 oncogene)) by  Jean-Loup Huret 

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