core binding factor acute myeloid leukemia A rearrangement (translocation) of genetic material involving the RUNX1 gene is found in approximately 7 percent of individuals with a form of blood cancer known as acute myeloid leukemia (AML). The translocation, written as t(8;21), combines genetic information from chromosome 21 and chromosome 8, fusing the RUNX1 gene on chromosome 21 with a gene on chromosome 8 called RUNX1T1 (also known as ETO). Because this genetic change affects CBF, the condition is classified as core binding factor AML (CBF-AML). The resulting fusion protein, RUNX1-ETO, is able to form CBF and attach to DNA, like the normal RUNX1 protein; however, instead of turning genes on, it turns them off. This change in gene activity blocks the maturation (differentiation) of blood cells and leads to the production of abnormal, immature white blood cells called myeloid blasts. While t(8;21) is important for leukemia development, a mutation in one or more additional genes is typically needed for the myeloid blasts to develop into cancerous leukemia cells. cytogenetically normal acute myeloid leukemia Genetics Home Reference provides information about cytogenetically normal acute myeloid leukemia. rheumatoid arthritis Genetics Home Reference provides information about rheumatoid arthritis. other disorders Translocations and other types of mutations involving the RUNX1 gene have been associated with different types of leukemia and related blood disorders, including acute lymphoblastic leukemia (ALL), chronic myelomonocytic leukemia (CMML), familial platelet disorder with predisposition to acute myeloid leukemia, and myelodysplastic syndromes (MDS). Depending on the type of mutation, these conditions can be related to impaired regulation of gene activity or loss of normal gene function. The RUNX1 gene mutations associated with these diseases are somatic mutations and are not inherited. They are found only in certain cells of the body.

     The RUNX1 gene provides instructions for making a protein called runt-related transcription factor 1 (RUNX1). Like other transcription factors, the RUNX1 protein attaches (binds) to specific regions of DNA and helps control the activity of particular genes. This protein interacts with another protein called core binding factor beta or CBFβ (produced from the CBFB gene), which helps RUNX1 bind to DNA and prevents it from being broken down. Together, these proteins form one version of a complex known as core binding factor (CBF). The RUNX1 protein turns on (activates) genes that help control the development of blood cells (hematopoiesis). In particular, it plays an important role in development of hematopoietic stem cells, early blood cells that have the potential to develop into all types of mature blood cells such as white blood cells, red blood cells, and platelets.

The following transcription factors affect gene expression:

• AML1a
• C/EBPalpha
• c-Myb
• p300
• Sox9
• GATA-2
• NF-1
• GATA-3
• Pax-5

Tissue specificity:

Expressed in all tissues examined except brain and heart. Highest levels in thymus, bone marrow and peripheral blood.

Caution:

The fusion of AML1 with EAP in T-MDS induces a change of reading frame in the latter resulting in 17 AA unrelated to those of EAP.

Molecular Function:

• Regulatory Region Dna Binding
• Rna Polymerase Ii Regulatory Region Sequence-Specific Dna Binding
• Core Promoter Binding
• Transcriptional Activator Activity, Rna Polymerase Ii Transcription Regulatory Region Sequence-Specific Binding
• Dna Binding
• Transcription Factor Activity, Sequence-Specific Dna Binding
• Calcium Ion Binding
• Atp Binding
• Transcription Factor Binding
• Protein Homodimerization Activity
• Protein Heterodimerization Activity

Biological Processes:

• Ossification
• Chondrocyte Differentiation
• Hemopoiesis
• Myeloid Cell Differentiation
• Negative Regulation Of Granulocyte Differentiation
• Positive Regulation Of Granulocyte Differentiation
• Positive Regulation Of Interleukin-2 Production
• Positive Regulation Of Angiogenesis
• Positive Regulation Of Transcription, Dna-Templated
• Positive Regulation Of Transcription From Rna Polymerase Ii Promoter
• Peripheral Nervous System Neuron Development
• Hematopoietic Stem Cell Proliferation