RUNX1T1

RUNX1T1, also known as RUNX1-RUNX1T1 or AML1-ETO, is a fusion gene product resulting from a chromosomal translocation, specifically the t(8;21)(q22;q22) translocation. This translocation is a recurrent genetic abnormality found in approximately 10-15% of acute myeloid leukemia (AML) cases, particularly in subtype M2 of the French-American-British (FAB) classification. The fusion protein is formed by the joining of the Runt-related transcription factor 1 (RUNX1) gene, located on chromosome 21, with the Translocated Transcript 1 (RUNX1T1) gene, also known as ETO (eight-twenty-one), located on chromosome 8.

The RUNX1T1 fusion protein acts as a dominant-negative regulator of RUNX1 transcriptional activity. RUNX1 is a crucial transcription factor involved in normal hematopoiesis, regulating the differentiation and proliferation of hematopoietic stem cells. The RUNX1T1 protein interferes with the normal function of RUNX1 by binding to its DNA recognition site and recruiting co-repressor complexes. This disruption of normal RUNX1 function is thought to be a key driver in the leukemogenesis process by impairing myeloid differentiation and promoting the accumulation of immature myeloid blasts. The presence of the RUNX1T1 fusion gene is often associated with a generally favorable prognosis in AML, although treatment strategies are tailored to individual patient characteristics.

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