RUNX1

RUNX1, also known as runt-related transcription factor 1 and, historically, AML1, is a transcription factor that plays a central role in hematopoiesis. It is a member of the RUNX family and functions as part of a heterodimer with the non-DNA-binding partner CBFβ, enabling high-affinity binding to target DNA sequences. RUNX1 is essential for definitive hematopoiesis, regulating the development and differentiation of hematopoietic stem and progenitor cells into myeloid and lymphoid lineages, with a particular impact on megakaryocyte and platelet formation.

The RUNX1 gene is located on chromosome 21q22.12 and produces multiple transcript variants encoding related protein isoforms. The protein contains a conserved Runt DNA-binding domain and activation and repression regions that modulate transcription of downstream genes involved in hematopoietic development. The RUNX1–CBFβ complex activates or represses gene expression in a context-dependent manner, coordinating lineage choice and maturation.

Clinical significance in hematologic disorders is notable. Somatic rearrangements of RUNX1 are common in leukemias. The t(8;21)(q22;q22) translocation generates the RUNX1–RUNX1T1 (AML1-ETO) fusion protein, which disrupts normal RUNX1 function and blocks differentiation, contributing to a subset of acute myeloid leukemia. In pediatric acute lymphoblastic leukemia, the t(12;21)(p13;q22) translocation yields ETV6–RUNX1 (TEL-AML1), a fusion associated with a favorable prognosis in many cohorts. Germline RUNX1 mutations cause familial platelet disorder with a predisposition to myeloid malignancies, presenting with platelet abnormalities and an elevated risk of AML or myelodysplastic syndrome.

RUNX1 remains a focus of research on transcriptional regulation in hematopoiesis and leukemogenesis.