This report describes acute myeloid leukemia, RUNX1-RUNX1T1 fusion, which is one of a number of subtypes of acute myeloid leukemia caused by specific translocations. The two human genes involved in this translocation are RUNX1 (also known as AML1), which encodes one of the components of the core binding factor (CFB) transcription factor complex, and RUNX1T1 (also known as ETO), a transcription factor. The fusion protein is able to associate into the CFB complex, which results in abnormal regulation of target genes.
The highest-scoring Drosophila ortholog of RUNX1 is run; the fly ortholog of RUNX1T1 is nvy. Neither fly gene has been characterized in the context of this disease model.
The Drosophila model of this disease is based on the introduction of UAS constructs of the human fusion gene (indicated as Hsap\RUNX1::Hsap\RUNX1T1) into flies. When expressed in embryonic hemocytes, differentiation of the blood cell lineage is inhibited, resulting in a dramatic increase in hematopoietic precursors.
[updated Feb. 2016 by FlyBase; FBrf0222196]
Acute myeloid leukemia (AML) is one of the most common types of leukemia among adults; it is uncommon under age 40. (Most childhood leukemias are acute lymphocytic leukemia, ALL). AML affects myeloid cells, resulting in an abundance of abnormal immature cells within the blood-cell-producing bone marrow; normal hematopoietic processes become increasingly compromised. Persons with AML are more likely to have infections and have an increased risk of bleeding as the numbers of healthy blood cells decrease. [from MedlinePlus; https://www.nlm.nih.gov/medlineplus/ency/article/000542.htm ]
See general description, above.
The most common translocation in core binding factor acute myeloid leukemia (CBF-AML) is t(8;21), which fuses a part of the RUNX1 gene (also known as AML1) on chromosome 21 with part of the RUNX1T1 gene (also known as ETO) on chromosome 8. [from Genetics Home Reference, Core binding factor acute myeloid leukemia]
RUNX1 encodes one of the components of the core binding factor (CFB) transcription factor complex. The RUNX1-RUNX1T1 fusion protein produced as a result of t(8;21) is able to form CBF and attach to DNA, like the normal RUNX1 protein. However, because the function of the transcription factor produced from the normal RUNX1T1 gene is to block gene activity, the abnormal CBF represses, rather than activates, transcription of the regulated genes. [from Genetics Home Reference, Core binding factor acute myeloid leukemia]
The RUNX1 gene encodes a Runt-related transcription factor; it plays a primary role in the development of all hematopoietic cell types. [from MIM:151385; 2016.02.03]
Many to one: 3 human to 1 Drosophila; additional orthologous genes in human are CBFA2T3 and CBFA2T2.