This report describes acute myeloid leukemia, CBFA2T3-GLIS2 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 CBFA2T3, a transcriptional repressor that facilitates transcriptional repression via its association with DNA-binding transcription factors and recruitment of other corepressors and histone-modifying enzymes, and GLIS2, a member of the GLI-similar zinc finger protein family, which can act either as a transcriptional repressor or as a transcriptional activator, depending on the cell context.
The Drosophila model of this disease is based on the introduction of UAS constructs of the human fusion gene (indicated as Hsap\ CBFA2T3::Hsap \GLIS2) into flies. Targeted expression of this human fusion gene in the wing disc results in an upregulation of the BMP signaling pathway.
[updated Aug. 2025 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 ]
Translocation between CBFA2T3 and GLIS2 results in a severe form of childhood acute myeloid leukemia (Gruber, et al. 2012, pubmed:23153540; FBrf0263059).
CBFA2T3 encodes a member of the myeloid translocation gene family which interact with DNA-bound transcription factors and recruit a range of corepressors to facilitate transcriptional repression. The t(16;21)(q24;q22) translocation is one of the less common karyotypic abnormalities in acute myeloid leukemia. The translocation produces a chimeric gene made up of the 5'-region of the runt-related transcription factor 1 gene fused to the 3'-region of this gene. This gene is also a putative breast tumor suppressor. [provided by RefSeq, Nov 2010]
GLIS2 is a member of the GLI-similar zinc finger protein family and encodes a nuclear transcription factor with five C2H2-type zinc finger domains. The protein encoded by this gene is widely expressed at low levels in the neural tube and peripheral nervous system and likely promotes neuronal differentiation. It is abundantly expressed in the kidney and may have a role in the regulation of kidney morphogenesis. p120 regulates the expression level of this protein and induces the cleavage of this protein's C-terminal zinc finger domain. This protein also promotes the nuclear translocation of p120..[provided by RefSeq, Jan 2010]
One to one (1 human to 1 Drosophila); GLIS2 has one moderate-scoring Drosophila ortholog, sug.
Many to one (3 human to 1 Drosophila); CBFA2T3 has one high-scoring Drosophila ortholog, nvy.
High-scoring ortholog of human CBFA2T2, CBFA2T3, and RUNX1T1 (1 Drosophila to 3 human).
Moderate-scoring ortholog of human FLIS2 (1 Drosophila to 1 human).
