RUNX1 (runt-related transcription factor 1 (acute myeloid leukemia 1; aml1 oncogene))
2003-01-01 Jean-Loup Huret , Sylvie Senon AffiliationGenetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France
Identity
HGNC
LOCATION
21q22.12
IMAGE
LEGEND
AML1 (21q22.3) in normal cells: clone dJ1107L6 - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.
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
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
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
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
Entity name
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
t(12;21)(q24;q22) AML --> ?/ RUNX1
Entity name
Disease
AML and therapy related AML; mainly with preceeding MDS
Prognosis
very poor
Entity name
Entity name
Entity name
t(20;21)(q1;3q22) treatment related ANL --> ? / RUNX1
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 11675361 | 2001 | A novel CBFA2 single-nucleotide mutation in familial platelet disorder with propensity to develop myeloid malignancies. | Buijs A et al |
| 10508502 | 1999 | A new angle on a pervasive oncogene. | Cleary ML et al |
| 10845943 | 2000 | A novel syndrome of radiation-associated acute myeloid leukemia involving AML1 gene translocations. | Hromas R et al |
| 10534769 | 1999 | Combined spectral karyotyping and DAPI banding analysis of chromosome abnormalities in myelodysplastic syndrome. | Kakazu N et al |
| 10825008 | 2000 | 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. | Mathew S et al |
| 11550288 | 2001 | Novel 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 |
| 11830488 | 2002 | 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. | Michaud J et al |
| 12072207 | 2002 | A new translocation that rearranges the AML1 gene in a patient with T-cell acute lymphoblastic leukemia. | Mikhail FM et al |
| 7795214 | 1995 | AML1 and the 8;21 and 3;21 translocations in acute and chronic myeloid leukemia. | Nucifora G et al |
| 8142622 | 1993 | Molecular basis of the t(8;21) translocation in acute myeloid leukaemia. | Ohki M et al |
| 11106827 | 2000 | Identification of two new translocations that disrupt the AML1 gene. | Richkind K et al |
| 7492786 | 1995 | High frequency of t(12;21) in childhood B-lineage acute lymphoblastic leukemia. | Romana SP et al |
| 9763573 | 1998 | CBFA2(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
Expression (GTEx)
Pathways
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 37742288 | 2024 | LncRNA H19 Inhibits Keratinocyte Cell Proliferation and Migration by Targeting miR-17-5p/RUNX1 Axis in Chronic Wounds. | 0 |
| 37967345 | 2024 | Hematopoietic Transcription Factor RUNX1 is Essential for Promoting Macrophage-Myofibroblast Transition in Non-Small-Cell Lung Carcinoma. | 3 |
| 38019014 | 2024 | Genomic landscape of patients with germline RUNX1 variants and familial platelet disorder with myeloid malignancy. | 1 |
| 38092960 | 2024 | RUNX1-IT1 acts as a scaffold of STAT1 and NuRD complex to promote ROS-mediated NF-κB activation and ovarian cancer progression. | 4 |
| 38172714 | 2024 | MYCT1 inhibits hematopoiesis in diffuse large B-cell lymphoma by suppressing RUNX1 transcription. | 0 |
| 38180714 | 2024 | Human umbilical cord mesenchymal stem cells overexpressing RUNX1 promote tendon-bone healing by inhibiting osteolysis, enhancing osteogenesis and promoting angiogenesis. | 0 |
| 38219493 | 2024 | Increased RUNX1 mutations in breast cancer disease progression. | 0 |
| 38330198 | 2024 | Altered platelet-megakaryocyte endocytosis and trafficking of albumin and fibrinogen in RUNX1 haplodeficiency. | 0 |
| 38367260 | 2024 | Clinical characteristics and prognosis of acute myeloid leukemia patients with Runt-related transcription factor 1 mutation: A single-center retrospective analysis. | 0 |
| 38610001 | 2024 | RUNX1-BMP2 promotes vasculogenic mimicry in laryngeal squamous cell carcinoma via activation of the PI3K-AKT signaling pathway. | 0 |
| 38616697 | 2024 | RUNX1 regulates promoter activity in the absence of cognate DNA binding motifs. | 0 |
| 38656651 | 2024 | A 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 |
| 38693222 | 2024 | The role of RUNX1/NF-κB in regulating PVAT inflammation in aortic dissection. | 0 |
| 38778047 | 2024 | RUNX1-induced upregulation of PTGS2 enhances cell growth, migration and invasion in colorectal cancer cells. | 0 |
| 37742288 | 2024 | LncRNA 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/runx1
Historical Card
1997-12-01 RUNX1 (runt-related transcription factor 1 (acute myeloid leukemia 1; aml1 oncogene)) by Jean-Loup Huret Affiliation
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 Affiliation
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France
