RUNX1-RUNX1T1 fusion protein (RUNX1-RUNX1T1)

The RUNX1-RUNX1T1 fusion protein is a chimeric transcription factor generated by the t(8;21)(q22;q22.1) chromosomal translocation, most commonly found in acute myeloid leukemia (AML)[1][2]. It comprises the DNA-binding domain (RHD) of RUNX1 (chromosome 21) and the transcriptional repression domains (NHR1–4) of RUNX1T1 (chromosome 8)[1]. The fusion protein acts as a dominant-negative regulator of normal hematopoietic differentiation by recruiting corepressor complexes—including histone deacetylases—to target genes, leading to transcriptional repression and chromatin remodeling. This promotes leukemogenesis by blocking myeloid differentiation, enhancing self-renewal, and modulating apoptosis and cell cycle progression[1][2][4]. RUNX1-RUNX1T1 also regulates alternative RNA splicing, further contributing to malignant transformation in AML[4]. Detection of the fusion transcript is a key biomarker for diagnosis, prognosis, and monitoring of minimal residual disease in t(8;21)-positive AML[1]. Therapeutic vulnerabilities include sensitivity to CDK4/6 and HDAC inhibitors, though clinical targeting of the fusion protein remains challenging due to its essential role in hematopoiesis and complex regulatory network[2][1].

Other names

RUNX1/AML1-ETORUNX1-ETOAML1-ETO fusion proteint(8;21) fusion protein

Inhibition of cell cycle regulators (e.g., CDK4/6) to counteract fusion-mediated cell proliferation; Epigenetic modulation via HDAC inhibition to disrupt fusion-driven gene silencing; Disruption of fusion protein DNA binding or associated protein complexes (investigational)