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
RUNX1
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
861
ALIAS
AML1,AML1-EVI-1,AMLCR1,CBF2alpha,CBFA2,EVI-1,PEBP2aB,PEBP2alpha
FUSION GENES
Show Gene Fusions

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
Entity name
t(1;21)(p36;q22) treatment related acute non lymphocytic leukemia (AML) --> ?/ RUNX1
Entity name
t(2;21)(p11;q22) AML --> ?/ RUNX1
Entity name
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 gene
5 AML1 - 3 EAP or MDS1 or EVI1
Entity name
t(4;21)(q31;q22) T-cell acute lymphoblastic leukemia (T-ALL) --> ?/ RUNX1
Entity name
t(5;21)(q13;q22) myelodysplastic syndrome (MDS) and AML --> ?/ RUNX1
Entity name
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 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
t(8;21)(q23;q22) MDS --> FOG2 / RUNX1
Entity name
t(8;21)(q24;q22) ALL and AML --> TRPS1 / RUNX1
Entity name
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 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
t(12;21)(q24;q22) AML --> ?/ RUNX1
Entity name
t(16;21)(q24;q22) AML --> MTG16- RUNX1
Disease
AML and therapy related AML; mainly with preceeding MDS
Prognosis
very poor
Entity name
t(17;21)(q11;q22) RUNX1
Entity name
t(19;21)(q13;q22) treatment related AML --> AMP19 / RUNX1
Entity name
t(20;21)(q1;3q22) treatment related ANL --> ? / RUNX1
Entity name
t(21;21)(q11;q22) MDS --> UPS25 / RUNX1

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
Adipose - Subcutaneous
Adipose - Visceral
Adrenal Gland
Artery - Aorta
Artery - Tibial
Bladder
Brain - Amygdala
Brain - Anterior cingulate cortex
Brain - Caudate
Brain - Cerebellar Hemisphere
Brain - Cerebellum
Brain - Cortex
Brain - Frontal Cortex
Brain - Hippocampus
Brain - Hypothalamus
Brain - Nucleus accumbens
Brain - Putamen
Brain - Spinal cord
Brain - Substantia nigra
Breast - Mammary Tissue
Cells - Cultured fibroblasts
Cells - EBV - transformed lymphocytes
Cervix - Ectocervix
Cervix - Endocervix
Colon - Sigmoid
Colon - Transverse
Esophagus - Gastroesophageal Junction
Esophagus - Mucosa
Esophagus - Muscularis
Fallopian Tube
Heart - Atrial Appendage
Heart - Left Ventricle
Kidney - Cortex
Kidney - Medulla
Liver
Lung
Minor Salivary Gland
Muscle - Skeletal
Nerve - Tibial
Ovary
Pancreas
Pituitary
Prostate
Skin - Not Sun Exposed
Skin - Sun Exposed
Small Intestine - Terminal Ileum
Spleen
Stomach
Testis
Thyroid
Uterus
Vagina
Whole Blood

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
cerebral cortex
cerebellum
hippocampus
caudate
thyroid gland
parathyroid gland
adrenal gland
nasopharynx
bronchus
lung
oral mucosa
salivary gland
esophagus
stomach 1
stomach 2
duodenum
small intestine
colon
rectum
liver
gallbladder
pancreas
kidney
urinary bladder
testis
epididymis
seminal vesicle
prostate
vagina
ovary
fallopian tube
endometrium 1
endometrium 2
cervix, uterine
placenta
breast
heart muscle
smooth muscle
skeletal muscle
soft tissue 1
soft tissue 2
adipose tissue
skin 1
skin 2
appendix
spleen
lymph node
tonsil
bone marrow

References

Pubmed IDYearTitleCitations
377422882024LncRNA H19 Inhibits Keratinocyte Cell Proliferation and Migration by Targeting miR-17-5p/RUNX1 Axis in Chronic Wounds.0
379673452024Hematopoietic Transcription Factor RUNX1 is Essential for Promoting Macrophage-Myofibroblast Transition in Non-Small-Cell Lung Carcinoma.3
380190142024Genomic landscape of patients with germline RUNX1 variants and familial platelet disorder with myeloid malignancy.1
380929602024RUNX1-IT1 acts as a scaffold of STAT1 and NuRD complex to promote ROS-mediated NF-κB activation and ovarian cancer progression.4
381727142024MYCT1 inhibits hematopoiesis in diffuse large B-cell lymphoma by suppressing RUNX1 transcription.0
381807142024Human umbilical cord mesenchymal stem cells overexpressing RUNX1 promote tendon-bone healing by inhibiting osteolysis, enhancing osteogenesis and promoting angiogenesis.0
382194932024Increased RUNX1 mutations in breast cancer disease progression.0
383301982024Altered platelet-megakaryocyte endocytosis and trafficking of albumin and fibrinogen in RUNX1 haplodeficiency.0
383672602024Clinical characteristics and prognosis of acute myeloid leukemia patients with Runt-related transcription factor 1 mutation: A single-center retrospective analysis.0
386100012024RUNX1-BMP2 promotes vasculogenic mimicry in laryngeal squamous cell carcinoma via activation of the PI3K-AKT signaling pathway.0
386166972024RUNX1 regulates promoter activity in the absence of cognate DNA binding motifs.0
386566512024A novel t(X;21)(p11.4;q22.12) translocation adds to the role of BCOR and RUNX1 in myelodysplastic syndromes and acute myeloid leukemias.0
386932222024The role of RUNX1/NF-κB in regulating PVAT inflammation in aortic dissection.0
387780472024RUNX1-induced upregulation of PTGS2 enhances cell growth, migration and invasion in colorectal cancer cells.0
377422882024LncRNA H19 Inhibits Keratinocyte Cell Proliferation and Migration by Targeting miR-17-5p/RUNX1 Axis in Chronic Wounds.0

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/gene-fusions/meetings/case-report-explorer/

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