The AML1 gene (also known as CBFA2 and RUNX1) is required for differentiation of hematopoietic cells and can act as a gene activator or repressor dependent on the association with either the corepressor Groucho or the HAT complex CBP/p300.
Pathology
germline mutations in familial platelet disorder associated with myeloid leukemia(MIM.601399)
gene variants associated with
- rheumatoid arthritis (MIM.180300)
- transient myeloproliferative disorder of Down syndrome
RUNX1 translocations (gene fusions) in leukemias
- FGA7/RUNX1 (FGA7/AML1) fusion gene by a t(4;21)(q28;q22) in T-cell acute lymphoblastic leukemia (TALL) (14695990)
- point mutations in the RUNX1/AML1 gene in RUNX leukemias (15156185)
- PRDM16/RUNX1 fusion gene by t(1;21)(p36;q22) in therapy-related acute myeloid leukemia (AML) (16015645)
- SH3D19/RUNX1 fusion gene ( 4q31.3) in acute myeloid leukemia (16858696)
- YTHDf2/RUNX1 fusion gene (1p35) in acute myeloid leukemia (16858696)
- ZNF687/RUNX1 fusion gene (1q21.2) in acute myeloid leukemia (16858696)
- ETO/RUNX1 fusion gene in acute myeloid leukemia
- The relatively common t(8;21) translocation fuses the DNA-binding domain of AML1 to ETO (eight-twenty-one), which in turn associates with gene repressors such as HDACs and Sin3. The AML1-ETO fusion suppresses AML1 target genes, leading to a block in myeloid differentiation and cellular transformation.
- RUNX1-MTG16 fusion gene in acute myeloblastic leukemia with t(16;21)(q24;q22)
List of RUNX1 partners in translocations (gene fusions) in leukemias
| AMP19 |
| CBFA2T3 |
| CPNE8 |
| ETO |
| ETV6 (TEL) |
| FGA7 |
| MTG16 |
| PRDM16 |
| PRDX4 |
| RPL22P1 (MDS1, EVI1) |
| SH3D19 |
| TRPS1 |
| USP25 |
| USP42 |
| YTHDF2 |
| ZNF687 |
| ZFPM12 |
References
Agerstam H, Lilljebjorn H, Lassen C, Swedin A, Richter J, Vandenberghe P, Johansson B, Fioretos T. Fusion gene-mediated truncation of RUNX1 as a potential mechanism underlying disease progression in the 8p11 myeloproliferative syndrome. Genes Chromosomes Cancer. 2007 Jul;46(7):635-43. PMID: 17394134
Mitani K. Molecular mechanisms of leukemogenesis by AML1/EVI-1. Oncogene. 2004 May 24;23(24):4263-9. PMID: 15156182
Peterson LF, Zhang DE. The 8;21 translocation in leukemogenesis. Oncogene. 2004 May 24;23(24):4255-62. PMID: 15156181
Anglin I, Passaniti A. Runx protein signaling in human cancers. Cancer Treat Res. 2004;119:189-215. PMID: 15164879